👤 J Ito

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Also published as: Junya Ito, M Ito, T. Ito
articles
Jiashuo Zheng, Weijia Zhang, Junya Ito +4 more · 2025 · Cell chemical biology · Elsevier · added 2026-04-20
N-acetyl-l-cysteine (NAC) is a medication and a widely used antioxidant in cell death research. Despite its somewhat obscure mechanism of action, its role in inhibiting ferroptosis is gaining increasi Show more
N-acetyl-l-cysteine (NAC) is a medication and a widely used antioxidant in cell death research. Despite its somewhat obscure mechanism of action, its role in inhibiting ferroptosis is gaining increasing recognition. In this study, we demonstrate that NAC treatment rapidly replenishes the intracellular cysteine pool, reinforcing its function as a prodrug for cysteine. Interestingly, its enantiomer, N-acetyl-d-cysteine (d-NAC), which cannot be converted into cysteine, also exhibits a strong anti-ferroptotic effect. We further clarify that NAC, d-NAC, and cysteine all act as direct reducing substrates for GPX4, counteracting lipid peroxidation. Consequently, only GPX4-rather than system xc-, glutathione biosynthesis, or ferroptosis suppressor protein 1-is necessary for NAC and d-NAC to prevent ferroptosis. Additionally, we identify a broad range of reducing substrates for GPX4 in vitro, including β-mercaptoethanol. These findings provide new insights into the mechanisms underlying the protective effects of NAC and other potential GPX4-reducing substrates against ferroptosis. Show less
no PDF DOI: 10.1016/j.chembiol.2025.04.002
Fe amino-acid prodrug
F Fadlallah, K Elshiwy, Y Elkeraie +1388 more · 2024 · World Journal of Clinical Oncology · added 2026-04-20
F Fadlallah, K Elshiwy, Y Elkeraie, Z Merjaneh, G Khoudari, MT Sarmini, M Gad, M Al-Husseini, A Saad, RL Siegel, KD Miller, NS Wagle, A Jemal, A Kumar, V Gautam, A Sandhu, K Rawat, A Sharma, L Saha, M Bretthauer, M Løberg, P Wieszczy, M Kalager, L Emilsson, K Garborg, M Rupinski, E Dekker, M Spaander, M Bugajski, Ø Holme, AG Zauber, ND Pilonis, A Mroz, EJ Kuipers, J Shi, MA Hernán, HO Adami, J Regula, G Hoff, MF Kaminski, S Shinji, T Yamada, A Matsuda, H Sonoda, R Ohta, T Iwai, K Takeda, K Yonaga, Y Masuda, H Yoshida, M Zajkowska, B Mroczko, GJ Poston, J Figueras, F Giuliante, G Nuzzo, AF Sobrero, JF Gigot, B Nordlinger, R Adam, T Gruenberger, MA Choti, AJ Bilchik, Cutsem EJ Van, JM Chiang, MI D'Angelica, GJ Chang, AM Kaiser, S Mills, JF Rafferty, WD Buie, JR Monson, MR Weiser, J Rafferty, AE Blackmore, MT Wong, CL Tang, BL Green, HC Marshall, F Collinson, P Quirke, P Guillou, DG Jayne, JM Brown, J Mar, A Anton-Ladislao, O Ibarrondo, A Arrospide, S Lázaro, N Gonzalez, M Bare, D Callejo, M Redondo, JM Quintana, S Kitano, M Inomata, J Mizusawa, H Katayama, M Watanabe, S Yamamoto, M Ito, S Saito, S Fujii, F Konishi, Y Saida, H Hasegawa, T Akagi, K Sugihara, T Yamaguchi, T Masaki, Y Fukunaga, K Murata, M Okajima, Y Moriya, Y Shimada, P Gavriilidis, K Katsanos, K Toritani, J Watanabe, K Nakagawa, Y Suwa, H Suwa, A Ishibe, M Ota, C Kunisaki, I Endo, T Matsuda, Y Sumi, K Yamashita, M Yamamoto, Y Matsuda, S Kanaji, T Oshikiri, T Nakamura, S Suzuki, Y Kakeji, RK Cleary, AM Morris, AL Halverson, KA Mirkin, AS Kulaylat, CS Hollenbeak, E Messaris, S Atallah, B Martin-Perez, M Albert, T deBeche-Adams, G Nassif, L Hunter, S Larach, MX Bjørn, SK Perdawood, Z Shen, Y Ye, Q Xie, K Jiang, S Wang, G Wang, Z Wang, Z Jiang, J Liu, J Zhao, J Li, A Arezzo, MA Bonino, F Ris, L Boni, E Cassinotti, DCC Foo, NF Shum, A Brolese, F Ciarleglio, DS Keller, R Rosati, Nardi P De, U Elmore, Romario U Fumagalli, MD Jafari, A Pigazzi, E Rybakov, M Alekseev, N Vettoretto, R Cirocchi, R Passera, E Forcignanò, M Morino, SH Park, HM Park, KR Baek, HM Ahn, IY Lee, GM Son, FA Vuijk, DE Hilling, JSD Mieog, AL Vahrmeijer, A Hiroishi, T Morimoto, K Horikoshi, Y Nakajima, KL Baglan, RC Frazier, D Yan, RR Huang, AA Martinez, JM Robertson, JG Letschert, JV Lebesque, Boer RW de, AA Hart, H Bartelink, JY Wo, CJ Anker, JB Ashman, NA Bhadkamkar, L Bradfield, DT Chang, J Dorth, J Garcia-Aguilar, D Goff, D Jacqmin, P Kelly, NB Newman, J Olsen, AC Raldow, E Ruiz-Garcia, KB Stitzenberg, CR Jr Thomas, QJ Wu, P Das, V Paroder, TJ Fraum, S Nougaret, I Petkovska, GM Rauch, H Kaur, C Bascoul-Mollevi, S Gourgou, C Borg, PL Etienne, E Rio, E Rullier, B Juzyna, F Castan, T Conroy, RR Bahadoer, EA Dijkstra, Etten B van, CAM Marijnen, H Putter, EM Kranenbarg, AGH Roodvoets, ID Nagtegaal, RGH Beets-Tan, LK Blomqvist, T Fokstuen, Tije AJ Ten, J Capdevila, MP Hendriks, I Edhemovic, A Cervantes, PJ Nilsson, B Glimelius, de Velde CJH van, GAP Hospers, P Goffredo, FF Quezada-Diaz, JJ Smith, A Cercek, CSD Roxburgh, P Strombom, LKF Temple, GM Nash, JG Guillem, PB Paty, R Yaeger, ZK Stadler, K Seier, M Gonen, NH Segal, DL Reidy, A Varghese, J Shia, E Vakiani, AJ Wu, CH Crane, MJ Gollub, LB Saltz, V Vendrely, J Asselineau, P Rouanet, JJ Tuech, A Valverde, Chaisemartin C de, M Rivoire, B Trilling, M Jafari, G Portier, B Meunier, I Sieleznieff, M Bertrand, F Marchal, A Dubois, M Pocard, A Rullier, D Smith, N Frulio, E Frison, Q Denost, CC Fossum, JY Alabbad, LB Romak, CL Hallemeier, MG Haddock, M Huebner, EJ Dozois, DW Larson, J Simpson, JH Scholefield, L Feo, M Polcino, E Vinet, N Joharatnam-Hogan, W Wilson, KK Shiu, GK Fusai, B Davidson, D Hochhauser, J Bridgewater, K Khan, JY Luh, KV Albuquerque, C Cheng, RP Ermoian, N Nabavizadeh, H Parsai, JC Roeske, SE Weiss, RB Wynn, Y Yu, SA Rosenthal, A Hartford, S Gwynne, R Webster, R Adams, S Mukherjee, B Coles, J Staffurth, AC Hartford, JM Galvin, DC Beyer, TJ Eichler, GS Ibbott, B Kavanagh, CJ Schultz, ST Chao, LK Dad, LA Dawson, NB Desai, M Pacella, R Rengan, Y Xiao, KM Yenice, BS Teh, SY Woo, EB Butler, SS Lo, AJ Fakiris, EL Chang, NA Mayr, JZ Wang, L Papiez, RC McGarry, HR Cardenes, RD Timmerman, AB Sharabi, PT Tran, M Lim, CG Drake, TL Deweese, E Lavrova, MD Garrett, YF Wang, C Chin, C Elliston, M Savacool, M Price, LA Kachnic, DP Horowitz, KK Brock, CH Chiang, TY Chao, MY Huang, M Haque, MS Shakil, KM Mahmud, EJ Vaios, J Yan, C Wang, X Jiang, Y Wei, Q Wang, K Cui, X Xu, F Wang, L Zhang, T Mitin, AL Zietman, X Tian, K Liu, Y Hou, J Cheng, J Zhang, Y Hiroshima, H Ishikawa, M Murakami, M Nakamura, S Shimizu, T Enomoto, T Oda, M Mizumoto, K Nakai, T Okumura, H Sakurai, G Kraft, S Yamada, H Takiyama, Y Isozaki, M Shinoto, H Makishima, N Yamamoto, H Tsuji, DK Ebner, T Kamada, EG Chiorean, G Nandakumar, T Fadelu, S Temin, AE Alarcon-Rozas, S Bejarano, AE Croitoru, S Grover, PV Lohar, A Odhiambo, ER Garcia, C Teh, A Rose, B Zaki, MD Chamberlin, Dominguez O Hernandez, S Yilmaz, SR Steele, D Duarte, N Vale, XH You, YH Jiang, Z Fang, F Sun, Y Li, W Wang, ZJ Xia, XZ Wang, HQ Ying, L Xiong, Y Lou, L Wang, NN Baxter, EB Kennedy, E Bergsland, J Berlin, TJ George, S Gill, PJ Gold, A Hantel, L Jones, C Lieu, N Mahmoud, YN You, JA Meyerhardt, WJ Thompson, GA Piazza, H Li, L Liu, J Fetter, B Zhu, G Sperl, D Ahnen, R Pamukcu, BN Islam, DD Browning, M Cruz-Burgos, A Losada-Garcia, CD Cruz-Hernández, SA Cortés-Ramírez, I Camacho-Arroyo, V Gonzalez-Covarrubias, M Morales-Pacheco, SI Trujillo-Bornios, M Rodríguez-Dorantes, P Dent, L Booth, JL Roberts, A Poklepovic, JF Hancock, N Arber, CJ Eagle, J Spicak, I Rácz, P Dite, J Hajer, M Zavoral, MJ Lechuga, P Gerletti, J Tang, RB Rosenstein, K Macdonald, P Bhadra, R Fowler, J Wittes, SD Solomon, B Levin, J Peñarando, A Cañas, LM López-Sánchez, F Conde, S Guil-Luna, V Hernández, C Villar, C Morales-Estévez, la Haba-Rodríguez J de, E Aranda, A Rodríguez-Ariza, RK Phillips, MH Wallace, PM Lynch, E Hawk, GB Gordon, BP Saunders, N Wakabayashi, Y Shen, S Zimmerman, L Godio, M Rodrigues-Bigas, LK Su, J Sherman, G Kelloff, G Steinbach, CA Burke, R Phillips, JS Morris, R Slack, X Wang, S Patterson, FA Sinicrope, MA Rodriguez-Bigas, E Half, S Bulow, A Latchford, S Clark, WA Ross, B Malone, H Hasson, E Richmond, D Fina, L Franchi, R Caruso, I Peluso, GC Naccari, S Bellinvia, R Testi, F Pallone, G Monteleone, A Reinacher-Schick, A Schoeneck, U Graeven, I Schwarte-Waldhoff, W Schmiegel, C Stolfi, J Słoka, M Madej, B Strzalka-Mrozik, AF Slater, JH Choi, JS Yoon, YW Won, BB Park, YY Lee, K Sasaki, NH Tsuno, E Sunami, K Kawai, K Hongo, M Hiyoshi, M Kaneko, K Murono, N Tada, T Nirei, K Takahashi, J Kitayama, M Selvakumaran, RK Amaravadi, IA Vasilevskaya, PJ O'Dwyer, LE Anselmino, MV Baglioni, G Reynoso, VR Rozados, OG Scharovsky, MJ Rico, M Menacho-Márquez, T André, C Boni, L Mounedji-Boudiaf, M Navarro, J Tabernero, T Hickish, C Topham, M Zaninelli, P Clingan, I Tabah-Fisch, Gramont A de, A Bonetti, F Rivera, JP Kuebler, HS Wieand, MJ O'Connell, RE Smith, LH Colangelo, G Yothers, NJ Petrelli, MP Findlay, TE Seay, JN Atkins, JL Zapas, JW Goodwin, L Fehrenbacher, RK Ramanathan, BA Conley, PJ Flynn, G Soori, LK Colman, EA Levine, KS Lanier, N Wolmark, A Figer, M Seymour, M Homerin, A Hmissi, J Cassidy, H Cortes-Funes, G Freyer, D Papamichael, Bail N Le, C Louvet, D Hendler, Braud F de, C Wilson, F Morvan, A Mohammed, NB Janakiram, M Brewer, K Vedala, VE Steele, CV Rao, AR Brás, P Fernandes, T Moreira, J Morales-Sanfrutos, E Sabidó, AMM Antunes, A Valente, A Preto, C Teixeira-Guedes, RG Teixeira, Garcia M Helena, TS Morais, P Florindo, MF Piedade, V Moreno, C Ciudad, V Noe, YT Lee, YJ Tan, CE Oon, VV Padma, Z Koveitypour, F Panahi, M Vakilian, M Peymani, Forootan F Seyed, Esfahani MH Nasr, K Ghaedi, N Valeri, C Dearman, S Rao, D Watkins, N Starling, I Chau, D Cunningham, J Neumann, L Wehweck, S Maatz, J Engel, T Kirchner, A Jung, Y Humblet, S Siena, D Khayat, H Bleiberg, A Santoro, D Bets, M Mueser, A Harstrick, C Verslype, Cutsem E Van, G Fornasier, S Francescon, P Baldo, CH Köhne, E Hitre, J Zaluski, Chien CR Chang, A Makhson, G D'Haens, T Pintér, R Lim, G Bodoky, JK Roh, G Folprecht, P Ruff, C Stroh, S Tejpar, M Schlichting, J Nippgen, P Rougier, I Láng, MP Nowacki, S Cascinu, I Shchepotin, J Maurel, A Zubel, I Celik, F Ciardiello, TS Maughan, RA Adams, CG Smith, AM Meade, MT Seymour, RH Wilson, S Idziaszczyk, R Harris, D Fisher, SL Kenny, E Kay, JK Mitchell, A Madi, B Jasani, MD James, MJ Kennedy, B Claes, D Lambrechts, R Kaplan, JP Cheadle, CJ Allegra, RB Rumble, SR Hamilton, PB Mangu, N Roach, RL Schilsky, VK Morris, AB 3rd Benson, M Cho, KK Ciombor, C Cremolini, A Davis, DA Deming, MG Fakih, S Gholami, TS Hong, I Jaiyesimi, K Klute, H Sanoff, JH Strickler, S White, JA Willis, C Eng, F Petrelli, R Ardito, A Ghidini, A Zaniboni, M Ghidini, S Barni, G Tomasello, L Lo, D Patel, AR Townsend, TJ Price, JY Douillard, R Burkes, M Barugel, J Jassem, I Kocákova, M Błasińska-Morawiec, M Šmakal, JL Canon, M Rother, KS Oliner, M Wolf, J Gansert, TW Kim, A Elme, JO Park, AA Udrea, SY Kim, JB Ahn, RV Valencia, S Krishnan, N Manojlovic, X Guan, C Lofton-Day, AS Jung, E Vrdoljak, D Rossini, A Boccaccino, M Carullo, C Antoniotti, G Dima, P Ciracì, F Marmorino, R Moretto, G Masi, T Liu, S Jiang, X Teng, L Zhong, M Liu, Y Jin, M Dong, Y Zhang, JY Zou, Y Wang, A Dasari, S Lonardi, R Garcia-Carbonero, E Elez, T Yoshino, A Sobrero, J Yao, P García-Alfonso, J Kocsis, Gracian A Cubillo, A Sartore-Bianchi, T Satoh, V Randrian, J Tomasek, G Chong, AS Paulson, T Masuishi, J Jones, T Csőszi, F Ghiringhelli, A Shergill, HS Hochster, J Krauss, A Bassam, M Ducreux, L Faugeras, S Kasper, D Arnold, S Nanda, Z Yang, WR Schelman, M Kania, D Dakowicz, R Bhattacharya, XC Ye, R Wang, X Ling, M McManus, F Fan, D Boulbes, LM Ellis, X Ye, L Xia, J Garcia, HI Hurwitz, AB Sandler, D Miles, RL Coleman, R Deurloo, OL Chinot, H Hurwitz, W Novotny, T Cartwright, J Hainsworth, W Heim, A Baron, S Griffing, E Holmgren, N Ferrara, G Fyfe, B Rogers, R Ross, F Kabbinavar, C Zhang, Y Lv, C Cao, J Lu, B Du, X Yang, Y Cui, Y Guo, R Lakomy, H Prenen, J Prausová, T Macarulla, Hazel GA van, V Moiseyenko, D Ferry, J McKendrick, J Polikoff, A Tellier, R Castan, C Allegra, A Thakur, MR Chorawala, RS Patel, AL Cohn, R Obermannova, TE Ciuleanu, DC Portnoy, A Grothey, P Garcia-Alfonso, K Yamazaki, PR Clingan, L Simms, SC Chang, F Nasroulah, P Ge, N Wan, X Han, X Long, Y Bian, Z Gao, Y Bao, Y Fan, G Chen, P Fu, J Ros, M Rodríguez-Castells, N Saoudi, I Baraibar, F Salva, E Élez, H Wasan, J Desai, F Loupakis, YS Hong, N Steeghs, TK Guren, HT Arkenau, A Gollerkeri, K Maharry, J Christy-Bittel, S Kopetz, DY Oh, YJ Bang, SJ Casak, MN Horiba, M Yuan, SJ Lemery, YL Shen, W Fu, JN Moore, Y Bi, D Auth, N Fesenko, PG Kluetz, R Pazdur, LA Fashoyin-Aje, T Vu, FX Claret, K Ng, C Wu, JM Hubbard, AL Coveler, C Fountzilas, A Kardosh, PM Kasi, HJ Lenz, DL Bajor, F Sanchez, M Stecher, W Feng, TS Bekaii-Saab, J Koury, M Lucero, C Cato, L Chang, J Geiger, D Henry, J Hernandez, F Hung, P Kaur, G Teskey, A Tran, Z Zhang, AS Shimu, HX Wei, Q Li, X Zheng, B Li, J Zheng, DM Pardoll, Y Shiravand, F Khodadadi, SMA Kashani, SR Hosseini-Fard, S Hosseini, H Sadeghirad, R Ladwa, K O'Byrne, A Kulasinghe, JA Seidel, A Otsuka, K Kabashima, HB Jie, Y Lei, N Gildener-Leapman, S Trivedi, T Green, LP Kane, RL Ferris, ME Keir, MJ Butte, GJ Freeman, AH Sharpe, M Wu, Q Huang, Y Xie, X Wu, H Ma, Y Xia, for Colorectal Cancer Immunotherapy, C for DE Research, LA Jr Diaz, BV Jensen, LH Jensen, C Punt, M Benavides, P Gibbs, la Fourchardiere C de, DT Le, WY Zhong, D Fogelman, P Marinello, T Andre, F Hirano, K Kaneko, H Tamura, H Dong, M Ichikawa, C Rietz, DB Flies, JS Lau, G Zhu, K Tamada, L Chen, MJ Overman, R McDermott, JL Leach, MA Morse, A Hill, M Axelson, RA Moss, MV Goldberg, ZA Cao, JM Ledeine, GA Maglinte, O Kooshkaki, A Derakhshani, N Hosseinkhani, M Torabi, S Safaei, O Brunetti, V Racanelli, N Silvestris, B Baradaran, V Singh, A Sheikh, MAS Abourehab, P Kesharwani, A GSK, M Lumish, J Sinopoli, J Weiss, M Lamendola-Essel, Dika IH El, N Segal, M Shcherba, R Sugarman, Z Stadler, B Rousseau, G Argiles, M Patel, A Desai, M Widmar, K Iyer, N Gianino, C Crane, PB Romesser, EP Pappou, P Paty, M Gollub, KA Schalper, T Watanabe, T Ishino, Y Ueda, J Nagasaki, T Sadahira, H Dansako, M Araki, Y Togashi, S Hashemzadeh, Z Asadzadeh, MA Shadbad, F Rasibonab, H Safarpour, V Jafarlou, AG Solimando, PK Singh, S Najafi, D Javadrashid, A Tarhini, KYM Wong, F Gelsomino, M Aglietta, MB Sawyer, A Hendlisz, B Neyns, S Abdullaev, A Memaj, M Lei, M Dixon, PM Boland, WW Ma, CH June, SR Riddell, TN Schumacher, A Mitra, A Barua, L Huang, S Ganguly, Q Feng, B He, H Du, J Yang, Q Zhang, J Shen, X Huang, M Wang, Y Huang, J Chen, Y Xu, W Zhao, Y Qi, Y Ou, C Qian, DJ Juat, SJ Hachey, J Billimek, Rosario MP Del, EL Nelson, CCW Hughes, JA Zell, E Martinis, C Ricci, C Trevisan, G Tomadini, S Tonon, Z Wu, M Yang, Y Cao, W Jia, T Zhang, H Huang, H Feng, Z Guo, Z Luo, X Ji, X Cheng, R Zhao, E Janssen, B Subtil, la Jara Ortiz F de, HMW Verheul, DVF Tauriello, Therapeutics Tizona, LLC Inc, Sankyo Co Daiichi, SE BioNTech, DS Neel, TG Bivona, A Bardelli, S Corso, A Bertotti, S Hobor, E Valtorta, G Siravegna, E Scala, A Cassingena, D Zecchin, M Apicella, G Migliardi, F Galimi, C Lauricella, C Zanon, T Perera, S Veronese, G Corti, A Amatu, M Gambacorta, M Sausen, VE Velculescu, P Comoglio, L Trusolino, Nicolantonio F Di, S Giordano, A Jahangiri, Lay M De, LM Miller, WS Carbonell, YL Hu, K Lu, MW Tom, J Paquette, TA Tokuyasu, S Tsao, R Marshall, A Perry, KM Bjorgan, MM Chaumeil, SM Ronen, G Bergers, MK Aghi, CJ LaFargue, P Amero, K Noh, LS Mangala, Y Wen, E Bayraktar, S Umamaheswaran, E Stur, SK Dasari, C Ivan, S Pradeep, W Yoo, C Lu, NB Jennings, V Vathipadiekal, W Hu, A Chelariu-Raicu, Z Ku, H Deng, W Xiong, HJ Choi, M Hu, T Kiyama, CA Mao, R Ali-Fehmi, MJ Birrer, N Zhang, G Lopez-Berestein, Franciscis V de, Z An, AK Sood, M Hao, S Hou, W Li, K Li, L Xue, Q Hu, L Zhu, Y Chen, H Sun, C Ju, YL Tang, DD Li, JY Duan, LM Sheng, J Manzi, CO Hoff, R Ferreira, A Pimentel, J Datta, AS Livingstone, R Vianna, P Abreu, GM Ramzy, M Norkin, T Koessler, L Voirol, M Tihy, D Hany, T McKee, N Buchs, M Docquier, C Toso, L Rubbia-Brandt, G Bakalli, S Guerrier, J Huelsken, P Nowak-Sliwinska, JD Fumet, A Hoos, AM Eggermont, S Janetzki, FS Hodi, R Ibrahim, A Anderson, R Humphrey, B Blumenstein, L Old, J Wolchok, F Tartari, M Santoni, L Burattini, P Mazzanti, A Onofri, R Berardi, J Zugazagoitia, C Guedes, S Ponce, I Ferrer, S Molina-Pinelo, L Paz-Ares, Velzen MJM van, S Derks, Grieken NCT van, Mohammad N Haj, Laarhoven HWM van, N Huyghe, P Baldin, den Eynde M Van, G Trimaglio, AF Tilkin-Mariamé, V Feliu, F Lauzéral-Vizcaino, M Tosolini, C Valle, M Ayyoub, O Neyrolles, N Vergnolle, Y Rombouts, C Devaud, AD Kostic, E Chun, L Robertson, JN Glickman, CA Gallini, M Michaud, TE Clancy, DC Chung, P Lochhead, GL Hold, EM El-Omar, D Brenner, CS Fuchs, M Meyerson, WS Garrett, LS Pessoa, M Heringer, VP Ferrer, Maghvan P Vaseghi, S Jeibouei, ME Akbari, V Niazi, F Karami, A Rezvani, N Ansarinejad, M Abbasinia, G Sarvari, H Zali, R Talaie, A Dey, S Pathak, S Prasad, AS Zhang, H Zhang, XF Sun, A Banerjee Show less
Colorectal cancer (CRC) is the third most common cancer worldwide, and the second most common cause of cancer-related death. In 2020, the estimated number of deaths due to CRC was approximately 930000 Show more
Colorectal cancer (CRC) is the third most common cancer worldwide, and the second most common cause of cancer-related death. In 2020, the estimated number of deaths due to CRC was approximately 930000, accounting for 10% of all cancer deaths worldwide. Accordingly, there is a vast amount of ongoing research aiming to find new and improved treatment modalities for CRC that can potentially increase survival and decrease overall morbidity and mortality. Current management strategies for CRC include surgical procedures for resectable cases, and radiotherapy, chemotherapy, and immunotherapy, in addition to their combination, for non-resectable tumors. Despite these options, CRC remains incurable in 50% of cases. Nonetheless, significant improvements in research techniques have allowed for treatment approaches for CRC to be frequently updated, leading to the availability of new drugs and therapeutic strategies. This review summarizes the most recent therapeutic approaches for CRC, with special emphasis on new strategies that are currently being studied and have great potential to improve the prognosis and lifespan of patients with CRC. Show less
📄 PDF DOI: 10.5306/wjco.v15.i9.1136
review
Li Xing, Shaohui Wang, H Sung +944 more · 2023 · Cell Death Discovery · Nature · added 2026-04-20
Li Xing, Shaohui Wang, H Sung, J Ferlay, RL Siegel, M Laversanne, I Soerjomataram, A Jemal, C Xia, X Dong, H Li, M Cao, D Sun, S He, W Cao, HD Chen, YW Yu, N Li, WQ Chen, BC Bade, CS Dela Cruz, AH Nielsen, U Fredberg, F Wu, L Wang, C Zhou, MI Toki, K Harrington, KN Syrigos, R Rosell, N Karachaliou, O Arrieta, RS Herbst, D Morgensztern, C Boshoff, ZF Lim, PC Ma, J Liu, M Hong, Y Li, D Chen, Y Wu, Y Hu, SJ Dixon, KM Lemberg, MR Lamprecht, R Skouta, EM Zaitsev, CE Gleason, J Li, F Cao, HL Yin, ZJ Huang, ZT Lin, N Mao, DH Manz, NL Blanchette, BT Paul, FM Torti, SV Torti, Y Mou, J Wang, J Wu, D He, C Zhang, C Duan, RS Hotchkiss, A Strasser, JE McDunn, PE Swanson, DL Vaux, D Moujalled, JR Liddell, ML Coleman, EA Sahai, M Yeo, M Bosch, A Dewar, MF Olson, M Suzanne, H Steller, X Chen, PB Comish, D Tang, R Kang, JR Hunt, MK Georgieff, IV Milto, IV Suhodolo, VD Prokopieva, TK Klimenteva, DJ Lane, AM Merlot, ML Huang, DH Bae, PJ Jansson, S Sahni, MW Hentze, MU Muckenthaler, B Galy, C Camaschella, D Galaris, A Barbouti, K Pantopoulos, T Nakamura, I Naguro, H Ichijo, C Yu, W Hou, Y Xie, X Song, X Sun, MT Lotze, HJ Zeh, A Donovan, CA Lima, JL Pinkus, GS Pinkus, LI Zon, S Robine, M Kruszewski, HB Dunford, A Hamaï, M Mehrpour, LJ Su, JH Zhang, H Gomez, R Murugan, X Hong, D Xu, S Doll, M Conrad, S Zalba, TL Ten Hagen, MP Wymann, R Schneiter, MM Gaschler, BR Stockwell, D Li, H Kuwata, S Hara, VE Kagan, G Mao, F Qu, JP Angeli, CS Croix, GE Winter, LS Musavi, ED Lee, B Snijder, M Rebsamen, P Vishnupriya, A Aparna, VP Viswanadha, WS Yang, KJ Kim, M Patel, MS Shchepinov, NK Singh, GN Rao, Y Zou, ET Graham, AA Deik, JK Eaton, W Wang, B Yan, Y Ai, Q Sun, Y Ma, Y Cao, H Lv, C Zhen, P Yang, L Hu, P Shang, J Lewerenz, SJ Hewett, Y Huang, M Lambros, PW Gout, PW Kalivas, H Sato, H Imai, M Matsuoka, T Kumagai, T Sakamoto, T Koumura, R SriRamaratnam, ME Welsch, K Shimada, VS Viswanathan, P Koppula, L Zhuang, B Gan, X Wang, Z Huang, Y Zhou, J Xia, W Hu, R Kong, N Wang, W Han, W Bao, J Lu, K Bersuker, JM Hendricks, Z Li, L Magtanong, B Ford, PH Tang, FP Freitas, R Shah, M Aldrovandi, MC da Silva, I Ingold, E Mishima, J Ito, Z Wu, A Wahida, C Mao, X Liu, Y Zhang, G Lei, Y Yan, H Lee, M Soula, RA Weber, O Zilka, H Alwaseem, K La, F Yen, VAN Kraft, CT Bezjian, S Pfeiffer, L Ringelstetter, C Müller, F Zandkarimi, J Vasquez-Vivar, Z Shi, S Tan, R Brigelius-Flohé, C Wang, Z Yang, Y Bai, T Shukuya, ME Poh, J Ni, K Chen, J Zhang, X Zhang, S Sui, L Zhang, S Xu, Z Wang, X Tian, Y Yang, L Ma, X Pan, Z Lin, D Jiang, Y Yu, D Yang, H Zhou, FJ Li, HZ Long, ZW Zhou, HY Luo, SG Xu, LC Gao, Z Fan, G Yang, W Zhang, Q Liu, G Liu, P Liu, L Feng, K Zhao, L Sun, X Yin, C Liu, M Chen, Y Jiang, Y Sun, X Wu, Z Sui, H Zhang, Y Wang, Z Yu, X Ji, J Qian, SMJ Rahman, PJ Siska, BK Harris, L Bai, L Zhi, Q Zhao, Y Chen, H Tian, J Jin, KR Zhang, YF Zhang, HM Lei, YB Tang, CS Ma, QM Lv, Y Xu, D Lv, C Yan, H Su, Y Shi, K Wang, J He, C Tu, H Xu, Y Lv, F He, L Antonucci, M Karin, E Panieri, L Saso, J Yang, Z Zhao, B Cao, S Yu, S Sajadimajd, M Khazaei, Z Ou, R Chen, X Niu, D Wu, J Duan, H Xiao, L Zhao, YP Kang, A Mockabee-Macias, C Jiang, A Falzone, N Prieto-Farigua, E Stone, W Liu, W Duan, J Song, S Wei, S Xia, H Wang, Q Huang, S Cheng, D Pei, B Proneth, YY Tyurina, E Panzilius, S Kobayashi, HL Zhang, BX Hu, ZL Li, T Du, JL Shan, ZP Ye, R Sha, C Yuan, X Sheng, J Peng, S Li, F Li, C Lv, QK Yang, H Wu, A Liu, J Hou, X Wen, C Li, S Xiong, T Yue, X Yang, X Hu, N Guo, YS Guan, Q He, Q Zou, L Yang, W Cui, Y Liu, QR Sun, L Jiang, N Kon, T Li, SJ Wang, T Su, H Hibshoosh, W Gu, G Kroemer, C Huang, M Yang, J Deng, P Li, W Su, R Jiang, W Yang, X He, Z Zhang, X Zheng, KR Marshall, M Gong, L Wodke, JH Lamb, DJ Jones, PB Farmer, L Kondiparthi, A Jo, JH Bae, YJ Yoon, TH Chung, EW Lee, YH Kim, JY Song, J Marszalek, EA Craig, EM Terzi, VO Sviderskiy, SW Alvarez, GC Whiten, R Possemato, T Papagiannakopoulos, AL Moreira, S Adams, KM Fujihara, BZ Zhang, TD Jackson, MO Ogunkola, B Nijagal, JV Milne, X Ye, C 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W Du, S Gao, D Wei, YQ Ke, P Duan, L Zhou, CY Wang, P Cao, Q Chen, Q Pan, H Gao, X Zhong, LS Kristensen, TB Hansen, MT Venø, J Kjems, G Shan, MS Andersen, LVW Stagsted, KK Ebbesen, FA Karreth, PP Pandolfi, Y Luo, Q Zhang, B Lv, Y Shang, O Li, J Kang, JJ Zhang, LW Hu, L Li, W Shanshan, M Hongying, F Jingjing, Y Yiming, R Yu, Y Rui, C Pan, K Wei, J Huang, Z Guo, Y Niu, X Xu, WX Peng, P Koirala, YY Mo, H Lu, S Wu, P Kim, X Zhou, J Yao, R Li, S Su, D Ye, W Lu, X Li, X Sui, N Hu, P Wang, G Xiu, M Wang, L Ouyang, W Lai, C Gai, M Yu, J Zheng, N Zhang, M Xu, T Chen, D Priem, G van Loo, MJM Bertrand, C Gao, F Xiao, Z Aburjania, S Jang, J Whitt, R Jaskula-Stzul, H Chen, JB Rose, J Xiao, M Liu, B Lian, N Vu, M Kim, D Stephenson, H MacKnight, C Chalfant, X Zeng, D Lu, M Yin, M Shan, Y Gao, S Liu, S Yan, J Zhu, R Lu, C Kang, K Tang, B Xu, Q Han, Y Xia, C Gong, AA Abdelgalil, HM Alkahtani, FI Al-Jenoobi, G Blumenschein, E Lachaier, C Louandre, C Godin, Z Saidak, M Baert, M Diouf, L Freire Boullosa, J Van Loenhout, T Flieswasser, J De Waele, C Hermans, H Lambrechts, W Zhou, M Yan, S Lian, K Sun, W Wu, Z Geng, H Bai, T Liu, B Zhang, H Yu, Z Han, Z Xu, C An, L Xu, H Xin, J Kryczka, KH Czarnecka-Chrebelska, E Brzeziańska-Lasota, L Galluzzi, L Senovilla, I Vitale, J Michels, I Martins, O Kepp, Z Liang, W Zhao, L Meng, Z Cui, C Abdel Shaheed, GE Ferreira, A Dmitritchenko, AJ McLachlan, RO Day, B Saragiotto, D Ding, J Laengle, J Kabiljo, L Hunter, J Homola, S Prodinger, G Egger, T Zhang, B Sun, C Zhong, K Xu, P Hofman, H Yan, H Liu, C Wu, LF Ye, KR Chaudhary, AD Harken, CJ Kinslow, PS Upadhyayula, CH Hsieh, HC Hsieh, FS Shih, PW Wang, LX Yang, DB Shieh, G Zhu, H Chi, Y Yin, H Diao, Z Liu, C Ge, S Zhang, H Mu, S Zheng, Z Tan, X Huang, US Neill, T Efferth, G Chen, F Benthani, D Liang, Z Bian, X Dai, W Chen, S Mo, H Yi, H Yao, L Lu, G He, M Wu, B Yuan, F Liao, Y Ren, X Deng, T Yang, N Han, X Peng, Q Ma, OA Ahmed Hamdi, SN Syed Abdul Rahman, K Awang, N Abdul Wahab, CY Looi, NF Thomas, R Zhang, T Pan, Y Xiang, M Zhang, H Xie, SW Ng, Y Chan, DK Chellappan, T Madheswaran, F Zeeshan, YL Chan, Y Fan, B Han, F Chen, S Alakurtti, T Mäkelä, S Koskimies, J Yli-Kauhaluoma, WY Yan, J Cai, JN Wang, YS Gong, XB Ding, KS Prabhu, AA Bhat, KS Siveen, S Kuttikrishnan, SS Raza, T Raheed, R Xu, J Tian, W Teng, D Boulghobra, PE Grillet, M Laguerre, M Tenon, J Fauconnier, P Fança-Berthon, M Shao, Q Jiang, C Shen, L Qiu, L Zhu, Y Lu, Z Sun, J Han, YY Zeng, YB Luo, XD Ju, YJ Cui, YB Pan, W Koch, W Kukula-Koch, Z Marzec, E Kasperek, L Wyszogrodzka-Koma, W Szwerc, Y Tsai, JC Merritt, SD Richbart, EG Moles, AJ Cox, KC Brown, SL Miles, K Srinivasan, XY Liu, DG Wei, RS Li, Q Wu, J Feng, L Yan, HQ Zhang, XF Xie, GM Li, JR Chen, MT Li, SL Morris-Natschke, KH Lee, CY Wu, YH Yang, YS Lin, GH Chang, MS Tsai, CM Hsu, S Chen, Y Guo, R Zhao, M Jiang, H Fu, UM Nazim, JK Jeong, SY Park, Q Gao, L Gu, A Gepdiremen, V Mshvildadze, H Süleyman, R Elias, D Wang, Y Lou, P Huang, M Jin, M Adnan, A Rasul, G Hussain, MA Shah, MK Zahoor, H Anwar, JS Lou, LP Zhao, ZH Huang, XY Chen, JT Xu, WC Tai, P Waiwut, A Inujima, H Inoue, I Saiki, H Sakurai, B Jiang, M Wan, A Vanduchova, P Anzenbacher, E Anzenbacherova, M Russo, C Spagnuolo, GL Russo, K Skalicka-Woźniak, M Daglia, E Sobarzo-Sánchez, Y Iida, M Okamoto-Katsuyama, S Maruoka, K Mizumura, T Shimizu, S Shikano, SM Lee, BS Bae, HW Park, NG Ahn, BG Cho, YL Cho, FG Zhai, QC Liang, YY Wu, JQ Liu, JW Liu, F Huang, J Pang, W Niu, YY Zhao, YQ Yang, HH Sheng, Q Tang, L Han, SM Wang, L Zeng, L Lignitto, SE LeBoeuf, H Homer, S Jiang, M Askenazi, TR Karakousi, M Yamamoto, TW Kensler, H Motohashi, W Cheng, M Guo, M Shen, D Kong, J Shao, C Liang, L Mahoney-Sánchez, H Bouchaoui, S Ayton, D Devos, JA Duce, JC Devedjian Show less
Lung cancer is a common malignant tumor that occurs in the human body and poses a serious threat to human health and quality of life. The existing treatment methods mainly include surgical treatment, Show more
Lung cancer is a common malignant tumor that occurs in the human body and poses a serious threat to human health and quality of life. The existing treatment methods mainly include surgical treatment, chemotherapy, and radiotherapy. However, due to the strong metastatic characteristics of lung cancer and the emergence of related drug resistance and radiation resistance, the overall survival rate of lung cancer patients is not ideal. There is an urgent need to develop new treatment strategies or new effective drugs to treat lung cancer. Ferroptosis, a novel type of programmed cell death, is different from the traditional cell death pathways such as apoptosis, necrosis, pyroptosis and so on. It is caused by the increase of iron-dependent reactive oxygen species due to intracellular iron overload, which leads to the accumulation of lipid peroxides, thus inducing cell membrane oxidative damage, affecting the normal life process of cells, and finally promoting the process of ferroptosis. The regulation of ferroptosis is closely related to the normal physiological process of cells, and it involves iron metabolism, lipid metabolism, and the balance between oxygen-free radical reaction and lipid peroxidation. A large number of studies have confirmed that ferroptosis is a result of the combined action of the cellular oxidation/antioxidant system and cell membrane damage/repair, which has great potential application in tumor therapy. Therefore, this review aims to explore potential therapeutic targets for ferroptosis in lung cancer by clarifying the regulatory pathway of ferroptosis. Based on the study of ferroptosis, the regulation mechanism of ferroptosis in lung cancer was understood and the existing chemical drugs and natural compounds targeting ferroptosis in lung cancer were summarized, with the aim of providing new ideas for the treatment of lung cancer. In addition, it also provides the basis for the discovery and clinical application of chemical drugs and natural compounds targeting ferroptosis to effectively treat lung cancer. Show less
📄 PDF DOI: 10.1038/s41420-023-01407-z
Fe ROS review
T. Narayan, A. Dutta, A. Agarwal +541 more · 2022 · iScience · Elsevier · added 2026-04-20
T. Narayan, A. Dutta, A. Agarwal, R.J. MacKenzie, R. Pippa, C.A. Eide, J. Oddo, J.W. Tyner, R. Sears, M.P. Vitek, M.D. Odero, D.J. Christensen, B.J. Druker, A. Ashkenazi, R.C. Pai, S. Fong, S. Leung, D.A. Lawrence, S.A. Marsters, C. Blackie, L. Chang, A.E. McMurtrey, A. Hebert, A. Bene, T.C. Chambers, I. Beuvink, A. Boulay, S. Fumagalli, F. Zilbermann, S. Ruetz, T. O'Reilly, F. Natt, J. Hall, H.A. Lane, G. Thomas, M. Bhat, N. Robichaud, L. Hulea, N. Sonenberg, J. Pelletier, I. Topisirovic, R. Briffa, S.P. Langdon, G. Grech, D.J. Harrison, B.A. Carneiro, W.S. El-Deiry, T.C. Chou, A.E. Collier, D.F. Spandau, R.C. Wek, I. Cristobal, R. Manso, R. Rincón, C. Caramés, C. Senin, A. Borrero, J. Martínez-Useros, M. Rodriguez, S. Zazo, O. Aguilera, R. Rincon, C. Carames, J. Madoz-Gurpide, F. Rojo, J. Garcia-Foncillas, R.M. De Palma, S.R. Parnham, Y. Li, J.J. Oaks, Y.K. Peterson, Z.M. Szulc, B.M. Roth, Y. Xing, B. Ogretmen, D. Deng, K. Shah, M.J. Fournier, L. Coudert, S. Mellaoui, P. Adjibade, C. Gareau, M.F. Côté, R.C. Gaudreault, R. Mazroui, A.M. Gaben, C. Saucier, M. Bedin, V. Barbu, J. Mester, C. Filion, D. Martel, Y. Labelle, A.G. Georgakilas, O.A. Martin, W.M. Bonner, M.J. Gerdes, C.J. Sevinsky, A. Sood, S. Adak, M.O. Bello, A. Bordwell, A. Can, A. Corwin, S. Dinn, R.J. Filkins, M. Gorospe, X. Wang, K.Z. Guyton, N.J. Holbrook, M.M. Gottesman, J.R. Graff, B.W. Konicek, J.H. Carter, E.G. Marcusson, R.S. Herbst, S.G. Eckhardt, R. Kurzrock, S. Ebbinghaus, P.J. O'Dwyer, M.S. Gordon, W. Novotny, M.A. Goldwasser, T.M. Tohnya, B.L. Lum, S.D. Heys, K.G. Park, M.A. McNurlan, A.G. Calder, V. Buchan, K. Blessing, O. Eremin, P.J. Garlick, B. Hoang, A. Benavides, Y. Shi, Y. Yang, P. Frost, J. Gera, A. Lichtenstein, A.N. Hobden, E. Cundliffe, N. Ikoma, K. Raghav, G. Chang, A. Ishitsuka, E. Fujine, Y. Mizutani, C. Tawada, H. Kanoh, Y. Banno, M. Seishima, S. Iwasaki, N.T. Ingolia, S.C. Jahn, P.E. Corsino, B.J. Davis, M.E. Law, P. Nørgaard, B.K. Law, V. Janssens, S. Longin, J. Goris, M.A. Jensen, V. Ferretti, R.L. Grossman, L.M. Staudt, Y.H. Jin, K.J. Yoo, Y.H. Lee, S.K. Lee, A. Kahvejian, Y.V. Svitkin, R. Sukarieh, M.N. M'Boutchou, S.K. Kelley, L.A. Harris, D. Xie, L. Deforge, K. Totpal, J. Bussiere, J.A. Fox, S.L. Kim, Y.C. Liu, Y.R. Park, S.Y. Seo, S.H. Kim, I.H. Kim, S.O. Lee, S.T. Lee, D.G. Kim, S.W. Kim, N.N. Kreis, F. Louwen, J. Yuan, M. Law, E. Forrester, A. Chytil, P. Corsino, G. Green, B. Davis, T. Rowe, B. Law, S.L. Lehman, G.J. Cerniglia, G.J. Johannes, J. Ye, S. Ryeom, C. Koumenis, S. Lek, J. Vargas-Medrano, E. Villanueva, B. Marcus, W. Godfrey, R.G. Perez, J. Lemke, S. von Karstedt, J. Zinngrebe, H. Walczak, D. Leonard, W. Huang, S. Izadmehr, C.M. O'Connor, D.D. Wiredja, Z. Wang, N. Zaware, Y. Chen, D.M. Schlatzer, J. Kiselar, V. Leung-Pineda, C.E. Ryan, H. Piwnica-Worms, L. Li, J. Wang, J.G. Li, Z. Wu, P. Ma, X.J. Lian, I.E. Gallouzi, H. Lin, X. Qiu, B. Zhang, J. Zhang, T.A. Lin, X. Kong, T.A.J. Haystead, A. Pause, G. Belsham, J.C. Lawrence, J. Lu, J.S. Kovach, F. Johnson, J. Chiang, R. Hodes, R. Lonser, Z. Zhuang, M. Mahyar-Roemer, K. Roemer, A. Maiuthed, C. Ninsontia, K. Erlenbach-Wuensch, B. Ndreshkjana, J.K. Muenzner, A. Caliskan, H. Ahmed P, A.P. Husayn, C. Chaotham, A. Hartmann, K. Malinowsky, U. Nitsche, K.P. Janssen, F.G. Bader, C. Spath, E. Drecoll, G. Keller, H. Hofler, S. Mazhar, S.E. Taylor, J. Sangodkar, G. Narla, K. McClinch, R.A. Avelar, D. Callejas, D. Wiredja, A. Perl, D.B. Kastrinsky, D. Schlatzer, M. Cooper, D.R. McIlwain, T. Berger, T.W. Mak, N. Melling, R. Simon, J.R. Izbicki, L.M. Terracciano, C. Bokemeyer, G. Sauter, A.H. Marx, J.R. Mills, Y. Hippo, F. Robert, S.M.H. Chen, A. Malina, C.J. Lin, U. Trojahn, H.G. Wendel, A. Charest, R.T. Bronson, C.S. Mitsiades, S.P. Treon, N. Mitsiades, Y. Shima, P. Richardson, R. Schlossman, T. Hideshima, K.C. Anderson, K. Morita, S. He, R.P. Nowak, M.W. Zimmerman, C. Fu, A.D. Durbin, M.W. Martel, N. Prutsch, N.S. Gray, S. Narayan, A.S. Jaiswal, R. Sharma, A. Nawab, L.V. Duckworth, M. Zajac-Kaye, T.J. George, J. Sharma, A.K. Sharma, R.A. Hromas, S. Ramisetti, A. Singh-Pillay, P. Singh, S. Amin, P. Palaiologos, D. Chrysikos, S. Theocharis, G. Kouraklis, G.J. Belsham, A.C. Gingras, O. Donzé, M.D. Ralff, P.G. Richardson, C. Eng, J. Kolesar, N.R. Rodrigues, A. Rowan, M.E. Smith, I.B. Kerr, W.F. Bodmer, J.V. Gannon, D.P. Lane, H.K. Roy, B.F. Olusola, D.L. Clemens, W.J. Karolski, A. Ratashak, H.T. Lynch, T.C. Smyrk, E. Rozengurt, H.P. Soares, J. Sinnet-Smith, P.P. Ruvolo, R. Tohme, E.K. Schmidt, G. Clavarino, M. Ceppi, P. Pierre, R.R. Sharma, T.S. Ravikumar, D. Raimo, W.L. Yang, R.L. Siegel, K.D. Miller, H.E. Fuchs, A. Jemal, J.C. Soria, Z. Márk, P. Zatloukal, B. Szima, I. Albert, E. Juhász, J.L. Pujol, J. Kozielski, N. Baker, D. Smethurst, W. Stöcklein, W. Piepersberg, A. Surov, P. Clauser, Y.W. Chang, L. Martincich, S.C. Partridge, J.Y. Kim, H.J. Meyer, A. Wienke, A. Suzuki, T. Ito, H. Kawano, M. Hayashida, Y. Hayasaki, Y. Tsutomi, K. Akahane, T. Nakano, M. Miura, K. Shiraki, T. Araki, S. Tahmasebi, T. Alain, V.K. Rajasekhar, J.P. Zhang, M. Prager-Khoutorsky, A. Khoutorsky, Y. Dogan, C.G. Gkogkas, E. Petroulakis, A. Sylvestre, A. Thorburn, K. Behbakht, H. Ford, H. Tian, E.K. Wittmack, T.J. Jorgensen, R. Tohmé, S. Gandhe, G. Tabaro, S. Vallabhaneni, A. Thomas, N. Vasireddi, N.S. Dhawan, A. Ma'ayan, N. Sharma, C. Vaklavas, S.W. Blume, W.E. Grizzle, K. Van der Jeught, H.C. Xu, Y.J. Li, X.B. Lu, G. Ji, A. Montinaro, R.E. Miller, K. Ariail, B. Gliniak, T.S. Griffith, M. Kubin, W. Chin, J. Jones, A. Woodward, T. Le, H. Wang, Y. Liu, J. Ding, Y. Huang, J. Liu, N. Liu, Y. Ao, Y. Hong, L. Wang, L. Zhang, M. Wang, E. Yaaghubi, A.F. Ghilardi, R.B. Ferreira, C.W. Chiang, O.A. Guryanova, D. Kopinke, C.D. Heldermon, S.S. Wang, E.D. Esplin, J.L. Li, L. Huang, A. Gazdar, J. Minna, G.A. Evans, X.W. Wang, Y.J. Zhang, J.S. Warmus, G.J. Dilley, A.I. Meyers, F. Wei, Y. Zhang, L. Geng, P. Zhang, G. Wang, R.H. Weiss, J. Westermarck, N. Wu, Z. Du, Y. Zhu, Y. Song, L. Pang, Z. Chen, J. Xu, P. Wang, H. Yang, J. Zhou, X. Li, W. Xue, C. Yu, Y. Tian, F. Zhu, J.Y. Zhou, W.Z. Wei, G.S. Wu, S.Q. Xu, P. Yaffee, A. Osipov, C. Tan, R. Tuli, A. Hendifar, L. Yong, Z. YuFeng, B. Guang, P.E. Young, C.M. Womeldorph, E.K. Johnson, J.A. Maykel, B. Brucher, A. Stojadinovic, I. Avital, A. Nissan, S.R. Steele, Y. Yu, S.S. Kanwar, B.B. Patel, J. Nautiyal, F.H. Sarkar, A.P. Majumdar, B. Fang, N. Fujita, T. Tsuruo, X. Zhou, W. Liu, X. Hu, A. Dorrance, R. Garzon, P.J. Houghton, C. Shen Show less
Summary The treatment of colorectal cancer (CRC) with FOLFOX shows some efficacy, but these tumors quickly develop resistance to this treatment. We have observed increased phosphorylation of AKT1/mTO Show more
Summary The treatment of colorectal cancer (CRC) with FOLFOX shows some efficacy, but these tumors quickly develop resistance to this treatment. We have observed increased phosphorylation of AKT1/mTOR/4EBP1 and levels of p21 in FOLFOX-resistant CRC cells. We have identified a small molecule, NSC49L, that stimulates protein phosphatase 2A (PP2A) activity, downregulates the AKT1/mTOR/4EBP1-axis, and inhibits p21 translation. We have provided evidence that NSC49L- and TRAIL-mediated sensitization is synergistically induced in p21-knockdown CRC cells, which is reversed in p21-overexpressing cells. p21 binds with procaspase 3 and prevents the activation of caspase 3. We have shown that TRAIL induces apoptosis through the activation of caspase 3 by NSC49L-mediated downregulation of p21 translation, and thereby cleavage of procaspase 3 into caspase 3. NSC49L does not affect global protein synthesis. These studies provide a mechanistic understanding of NSC49L as a PP2A agonist, and how its combination with TRAIL sensitizes FOLFOX-resistant CRC cells. Show less
📄 PDF DOI: 10.1016/j.isci.2022.104518
amino-acid synthesis