👤 M Hardy

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6
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5
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Also published as: AB Hardy, M. F. Hardy, M. Hardy, Micael Hardy
articles
H Zhou, J Ferlay, RL Siegel +660 more · 2025 · Oncology Reports · added 2026-04-20
H Zhou, J Ferlay, RL Siegel, M Laversanne, I Soerjomataram, A Jemal, F Bray, PS Steeg, KD Miller, HE Fuchs, FX Xu, YL Zhang, JJ Liu, DD Zhang, HB Chen, K Saxena, MK Jolly, JA Bertout, SA Patel, MC Simon, X Meng, FM Kong, J Yu, A Challapalli, L Carroll, EO Aboagye, DC Hinshaw, LA Shevde, P Desai, N Takahashi, R Kumar, S Nichols, J Malin, A Hunt, C Schultz, Y Cao, D Tillo, D Nousome, FF Tam, KL Ning, M Lee, JM Dumlao, JC Choy, AA Tirpe, D Gulei, SM Ciortea, C Crivii, I Berindan-Neagoe, EB Rankin, AJ Giaccia, GN Masoud, W Li, Y Della Rocca, L Fonticoli, TS Rajan, O Trubiani, S Caputi, F Diomede, J Pizzicannella, GD Marconi, SG Zeng, X Lin, JC Liu, J Zhou, RY Hapke, SM Haake, S Musleh Ud Din, SG Streit, BT Huynh, C Hana, AN Abraham, A Hussein, S Liu, Y Zhan, J Luo, J Feng, J Lu, H Zheng, Q Wen, S Fan, C Wang, S Xu, X Yang, W Luo, H Hu, R Chang, J Zhong, M Knabel, R O'Meally, RN Cole, A Pandey, GL Semenza, Y Wei, D Wang, F Jin, Z Bian, L Li, H Liang, M Li, L Shi, C Pan, D Zhu, X Ji, R Zhu, C Gao, H Xie, X Gong, H Jiang, H Zhao, M Zhang, Y He, X Li, Y Xu, X Liu, S Jiang, R Wang, H Yan, L Jin, X Dou, D Chen, V Becker, X Yuan, AS Boewe, E Ampofo, E Ebert, J Hohneck, RM Bohle, E Meese, Y Zhao, MD Menger, J Zhao, CR Qiao, Z Ding, YL Sheng, XN Li, Y Yang, DY Zhu, CY Zhang, DL Liu, K Wu, S Zhao, C Han, Y Zhang, F Liu, J Ren, HL Yin, HW Xu, QY Lin, RD Leone, JD Powell, Z Yu, J Zou, F Xu, J Jin, G Yu, J Gu, S Yang, X Wang, Y Wu, J Wei, J Xu, AL Jackson, B Zhou, WY Kim, KL Eales, KER Hollinshead, DA Tennant, E Dai, W Wang, Y Li, D Ye, R Courtnay, DC Ngo, N Malik, K Ververis, SM Tortorella, TC Karagiannis, F Luo, N Yan, S Li, G Cao, Q Cheng, Q Xia, H Wang, S Shang, MZ Wang, Z Xing, N He, H Nisar, PM Sanchidrián González, M Brauny, FM Labonté, C Schmitz, MD Roggan, B Konda, CE Hellweg, Z Guo, L Hu, Q Wang, Y Wang, XP Liu, C Chen, W Hu, X Zhang, C Liang, C Wu, S Wan, L Xu, S Wang, J Wang, X Huang, C Zhang, L Zhou, Y Du, C Li, H Ren, L Zheng, PE Porporato, N Filigheddu, JMB Pedro, G Kroemer, L Galluzzi, OT Brustugun, RX Huang, PK Zhou, H Chen, Z Han, Q Luo, Q Li, H Zuo, L Gong, C Liu, S Han, T Zhou, LY Zhang, JZ He, ZM Miao, YY Li, YM Zhang, ZW Liu, SZ Zhang, Y Chen, GC Zhou, YQ Liu, LH Gray, AD Conger, M Ebert, S Hornsey, OC Scott, AB Herrera-Campos, E Zamudio-Martinez, D Delgado-Bellido, M Fernández-Cortés, LM Montuenga, FJ Oliver, A Garcia-Diaz, Q Guo, F Lan, X Yan, Z Xiao, Q Zhang, S Roy, S Kumaravel, A Sharma, CL Duran, KJ Bayless, S Chakraborty, CY Hu, CF Hung, PC Chen, JY Hsu, CT Wang, MD Lai, YS Tsai, AL Shiau, GS Shieh, CL Wu, A Mancino, T Schioppa, P Larghi, F Pasqualini, M Nebuloni, IH Chen, S Sozzani, JM Austyn, A Mantovani, A Sica, X Peng, J Huang, Y Tao, HK Eltzschig, LF Thompson, J Karhausen, RJ Cotta, JC Ibla, SC Robson, SP Colgan, J Li, L Wang, X Chen, Y Ping, L Huang, D Yue, Z Zhang, F Wang, SM An, HM Lei, XP Ding, F Sun, YB Tang, HZ Chen, Y Shen, L Zhu, A Kogita, Y Togashi, H Hayashi, S Sogabe, M Terashima, MA De Velasco, K Sakai, Y Fujita, S Tomida, Y Takeyama, S Karan, MY Cho, H Lee, HS Park, M Sundararajan, JL Sessler, KS Hong, MHY Cheng, Y Mo, G Zheng, LC Clark, R Wolf, D Granger, Z Taylor, X Sun, G Niu, N Chan, B Shen, MV Shirmanova, MM Lukina, MA Sirotkina, LE Shimolina, VV Dudenkova, NI Ignatova, S Tobita, VI Shcheslavskiy, EV Zagaynova, JM Vanderkooi, G Maniara, TJ Green, DF Wilson, CJ Koch, SM Evans, MR Horsman, BS Sørensen, M Busk, DW Siemann, C Huang, J Liang, X Lei, X Xu, L Luo, X Hu, J Gou, W Lin, F Yang, C Liao, D Nasri, R Manwar, A Kaushik, EE Er, K Avanaki, KA Krohn, JM Link, RP Mason, JR Brender, Y Saida, N Devasahayam, MC Krishna, S Kishimoto, I Godet, S Doctorman, F Wu, DM Gilkes, K Matsumoto, JB Mitchell, W Qin, C Xu, C Yu, S Shen, W Huang, DS Vikram, JL Zweier, P Kuppusamy, B Epel, MK Bowman, C Mailer, HJ Halpern, B Hao, H Dong, R Xiong, C Song, N Li, Q Geng, R Zhang, L Lai, J He, D You, W Duan, X Dong, Y Zhu, L Lin, C Ostheimer, M Bache, A Güttler, M Kotzsch, D Vordermark, A Giatromanolaki, AL Harris, AH Banham, CA Contrafouris, MI Koukourakis, H Geng, L Chen, S Lv, SJ Kim, ZN Rabbani, RT Vollmer, EG Schreiber, E Oosterwijk, MW Dewhirst, Z Vujaskovic, MJ Kelley, D Coppola, M Szabo, D Boulware, P Muraca, M Alsarraj, AF Chambers, TJ Yeatman, T Reese, K Stępień, RP Ostrowski, E Matyja, SW Kim, IK Kim, JH Ha, CD Yeo, HH Kang, JW Kim, SH Lee, O Thews, P Vaupel, M Heyboer, D Sharma, W Santiago, N McCulloch, LW Jones, BL Viglianti, JA Tashjian, SM Kothadia, ST Keir, SJ Freedland, MQ Potter, EJ Moon, T Schroeder, JE Herndon, S Jo, J Jeon, G Park, HK Do, J Kang, KJ Ahn, SY Ma, YM Choi, D Kim, B Youn, Y Ki, P Ghosh, C Vidal, S Dey, L Zhang, TM Ashton, WG McKenna, LA Kunz-Schughart, GS Higgins, B Kalyanaraman, G Cheng, M Hardy, M You, M Shameem, AJ Bagherpoor, A Nakhi, P Dosa, G Georg, F Kassie, M Skwarski, DR McGowan, E Belcher, F Di Chiara, D Stavroulias, M McCole, JL Derham, KY Chu, E Teoh, J Chauhan, M Benej, X Hong, S Vibhute, S Scott, J Wu, E Graves, QT Le, AC Koong, B Yu, S Sohoni, T Wang, SP Kalainayakan, PC Konduri, A Ashrafi, P Modareszadeh, N Salamat, PS Alemi, E Berisha, TW Secomb, V Sukhatme, G Bouche, L Meheus, VP Sukhatme, P Pantziarka, BJT Reymen, MW van Gisbergen, AJG Even, CML Zegers, M Das, E Vegt, JE Wildberger, FM Mottaghy, A Yaromina, LJ Dubois, PP Wong, N Bodrug, KM Hodivala-Dilke, S Guelfi, K Hodivala-Dilke, G Bergers, C Wigerup, S Påhlman, D Bexell, Y Xia, HK Choi, K Lee, L Iommarini, AM Porcelli, G Gasparre, I Kurelac, N Albadari, S Deng, J Ma, K Cao, X Ling, P Zhang, J Zhu, H Deng, P Li, Q Hang, Y Jin, M Chen, MS Lara, CM Blakely, JW Riess, H Zhu, S Zhang, W Tian, C Cao, L Shu, A Mahdi, B Darvishi, K Majidzadeh-A, M Salehi, L Farahmand, Z Xie, T Zou, JL Bryant, SL Meredith, KJ Williams, A White, WR Wilson, MP Hay, SX Chen, J Zhang, F Xue, W Liu, Y Kuang, B Gu, S Song, F Shepherd, G Koschel, J Von Pawel, U Gatzmeier, N Van Zandwiyk, P Woll, R Van Klavren, P Krasko, P Desimone, M Nicolson, L Marcu, I Olver, K Graham, E Unger, D Lindsay, CM Garvey, SM Mumenthaler, J Foo, C Meaney, GG Powathil, P Lambin, M Kohandel, BT Oronsky, SJ Knox, JJ Scicinski, B Oronsky, J Scicinski, S Ning, D Peehl, A Oronsky, P Cabrales, M Bednarski, S Knox, L Zhao, C Shen, Y Luo, X Hou, Y Qi, Z Huang, L Gao, M Wu, Y Zhou, X Feng, Z Wu, X Rao, R Zhou, R Meng, P Dey, R Das, S Chatterjee, R Paul, U Ghosh, Y Demizu, O Fujii, H Iwata, N Fuwa, SM Bentzen, V Gregoire, G Meijer, J Steenhuijsen, M Bal, K De Jaeger, D Schuring, J Theuws Show less
Non-small cell lung cancer (NSCLC) is one of the most prevalent and lethal types of cancers worldwide and its high incidence and mortality rates pose a significant public health challenge. Despite sig Show more
Non-small cell lung cancer (NSCLC) is one of the most prevalent and lethal types of cancers worldwide and its high incidence and mortality rates pose a significant public health challenge. Despite significant advances in targeted therapy and immunotherapy, the overall prognosis of patients with NSCLC remains poor. Hypoxia is a critical driving factor in tumor progression, influencing the biological behavior of tumor cells through complex molecular mechanisms. The present review systematically examined the role of the hypoxic microenvironment in NSCLC, demonstrating its crucial role in promoting tumor cell growth, invasion and metastasis. Additionally, it has been previously reported that the hypoxic microenvironment enhances tumor cell resistance by activating hypoxia-inducible factor and regulating exosome secretion. The hypoxic microenvironment also enables tumor cells to adapt to low oxygen and nutrient-deficient conditions by enhancing metabolic reprogramming, such as through upregulating glycolysis. Further studies have shown that the hypoxic microenvironment facilitates immune escape by modulating tumor-associated immune cells and suppressing the antitumor response of the immune system. Moreover, the hypoxic microenvironment increases tumor resistance to radiotherapy, chemotherapy and other types of targeted therapy through various pathways, significantly reducing the therapeutic efficacy of these treatments. Therefore, it could be suggested that early detection of cellular hypoxia and targeted therapy based on hypoxia may offer new therapeutic approaches for patients with NSCLC. The present review not only deepened the current understanding of the mechanisms of action and role of the hypoxic microenvironment in NSCLC but also provided a solid theoretical basis for the future development of precision treatments for patients with NSCLC. Show less
📄 PDF DOI: 10.3892/or.2024.8862
anticancer review
PN Beerkens, J Bussink, TW Secomb +159 more · 2024 · Cancer & Metabolism · BioMed Central · added 2026-04-20
PN Beerkens, J Bussink, TW Secomb, R Hsu, ET Ong, JF Gross, MW Dewhirst, JM Brown, DF Boreel, PN Span, S Heskamp, GJ Adema, SE Rademakers, JH Kaanders, FC Sweep, AJ van der Kogel, MC Joiner, DR Grimes, M Partridge, JT Coates, M Skwarski, GS Higgins, US Gaipl, G Multhoff, H Scheithauer, K Lauber, S Hehlgans, B Frey, TM Ashton, E Fokas, LA Kunz-Schughart, LK Folkes, S Anbalagan, M Huether, KTY Han, A Fyles, T Shek, J Croke, N Dhani, D D’Souza, DR McGowan, E Belcher, F Di Chiara, D Stavroulias, M McCole, TA Yap, N Daver, M Mahendra, J Zhang, C Kamiya-Matsuoka, F Meric-Bernstam, F Janku, P LoRusso, AS Mansfield, R Nanda, A Spira, T Wang, G Cheng, M Hardy, P Topchyan, R Zander, P Volberding, W Cui, J Zielonka, O Ouari, M Lopez, D McAllister, K Boyle, J Joseph, A Sikora, J Vasquez-Vivar, IC Summerhayes, TJ Lampidis, SD Bernal, JJ Nadakavukaren, KK Nadakavukaren, EL Shepherd, JS Modica-Napolitano, JR Aprille, FM Veronese, G Pasut, M Busk, J Overgaard, MR Horsman, J Lok, SP Burr, AS Costa, GL Grice, RT Timms, IT Lobb, P Freisinger, LD Falo, M Kovacsovics-Bankowski, K Thompson, KL Rock, K Rohlenova, K Sachaphibulkij, J Stursa, A Bezawork-Geleta, J Blecha, B Endaya, Z Bielcikova, L Krizova, L Dong, J Spacek, S Hlousek, A Nagelkerke, FCGJ Sweep, JM Newton, A Hanoteau, HC Liu, A Gaspero, F Parikh, RD Gartrell-Corrado, JM Henk, PB Kunkler, CW Smith, GO Janssens, CH Terhaard, PA Doornaert, HP Bijl, P van den Ende, JR Molina, Y Sun, M Protopopova, S Gera, M Bandi, C Bristow, T Lofton, M Smith, CA Bristow, A Carugo, M Benej, X Hong, S Vibhute, S Scott, J Wu, E Graves, S Nadanaciva, A Bernal, R Aggeler, R Capaldi, Y Will, QY Li, Y Huang, M Fiorillo, R Lamb, HB Tanowitz, L Mutti, M Krstic-Demonacos, AR Cappello, M Huang, D Xiong, J Pan, Q Zhang, Y Wang, CR Myers, RP Garay, R El-Gewely, JK Armstrong, G Garratty, P Richette Show less
Background Hypoxia is a common feature of many solid tumors and causes radiotherapy and immunotherapy resistance. Pharmacological inhibition of oxidative phosphorylation (OXPHOS) has emerged as a the Show more
Background Hypoxia is a common feature of many solid tumors and causes radiotherapy and immunotherapy resistance. Pharmacological inhibition of oxidative phosphorylation (OXPHOS) has emerged as a therapeutic strategy to reduce hypoxia. However, the OXPHOS inhibitors tested in clinical trials caused only moderate responses in hypoxia alleviation or trials were terminated due to dose-limiting toxicities. To improve the therapeutic benefit, FDA approved OXPHOS inhibitors (e.g. atovaquone) were conjugated to triphenylphosphonium (TPP + ) to preferentially target cancer cell’s mitochondria. In this study, we evaluated the hypoxia reducing effects of several mitochondria-targeted OXPHOS inhibitors and compared them to non-mitochondria-targeted OXPHOS inhibitors using newly developed spheroid models for diffusion-limited hypoxia. Methods B16OVA murine melanoma cells and MC38 murine colon cancer cells expressing a HIF-Responsive Element (HRE)-induced Green Fluorescent Protein (GFP) with an oxygen-dependent degradation domain (HRE-eGFP-ODD) were generated to assess diffusion-limited hypoxia dynamics in spheroids. Spheroids were treated with IACS-010759, atovaquone, metformin, tamoxifen or with mitochondria-targeted atovaquone (Mito-ATO), PEGylated mitochondria-targeted atovaquone (Mito-PEG-ATO) or mitochondria-targeted tamoxifen (MitoTam). Hypoxia dynamics were followed and quantified over time using the IncuCyte Zoom Live Cell-Imaging system. Results Hypoxic cores developed in B16OVA.HRE and MC38.HRE spheroids within 24 h hours after seeding. Treatment with IACS-010759, metformin, atovaquone, Mito-PEG-ATO and MitoTam showed a dose-dependent reduction of hypoxia in both B16OVA.HRE and MC38.HRE spheroids. Mito-ATO only alleviated hypoxia in MC38.HRE spheroids while tamoxifen was not able to reduce hypoxia in any of the spheroid models. The mitochondria-targeted OXPHOS inhibitors demonstrated stronger anti-hypoxic effects compared to the non-mito-targeted OXPHOS inhibitors. Conclusions We successfully developed a high-throughput spheroid model in which hypoxia dynamics can be quantified over time. Using this model, we showed that the mitochondria-targeted OXPHOS inhibitors Mito-ATO, Mito-PEG-ATO and MitoTam reduce hypoxia in tumor cells in a dose-dependent manner, potentially sensitizing hypoxic tumor cells for radiotherapy. Supplementary Information The online version contains supplementary material available at 10.1186/s40170-024-00342-6. Show less
📄 PDF DOI: 10.1186/s40170-024-00342-6
amino-acid imaging mitochondria
L.A. Zhou, Q. Zhou, M.D. Siegelin +351 more · 2024 · Cells · MDPI · added 2026-04-20
L.A. Zhou, Q. Zhou, M.D. Siegelin, J.M. Angelastro, P. Paerhati, J. Liu, Z. Jin, T. Jakos, S. Zhu, L. Qian, J. Zhu, Y. Yuan, P.D. Canoll, J. Kuo, M. Weicker, A. Costa, J.N. Bruce, L.A. Greene, T.K. Sears, M. Zhang, X. Wang, N. Yang, X. Zhu, Z. Lu, Y. Cai, B. Li, Y. Zhu, X. Li, Y. Wei, K.H. Klempnauer, X. Sun, P. Jefferson, S. Wang, J. Wu, W. Zhao, M. Li, S. Li, L. Hartl, J. Duitman, M.F. Bijlsma, C.A. Spek, C.C. Cates, A.D. Arias, L.S. Nakayama Wong, M.W. Lame, M. Sidorov, G. Cayanan, D.J. Rowland, J. Fung, G. Karpel-Massler, B.A. Horst, C. Shu, L. Chau, T. Tsujiuchi, P. Canoll, N. Pasquier, T.T.T. Nguyen, D. Banerjee, S. Boboila, S. Okochi, A.V. Kadenhe-Chiweshe, G. Lopez, A. Califano, E.P. Connolly, D.J. Yamashiro, S.E. Monaco, M. Szabolcs, D. Merino, P. Vaupel, G. Multhoff, A. Fukushi, H.D. Kim, Y.C. Chang, C.H. Kim, M. Jaworska, J. Szczudlo, A. Pietrzyk, J. Shah, S.E. Trojan, B. Ostrowska, K.A. Kocemba-Pilarczyk, T. Ackermann, G. Hartleben, C. Muller, G. Mastrobuoni, M. Groth, B.A. Sterken, M.A. Zaini, S.A. Youssef, H.R. Zuidhof, S.R. Krauss, Z. Wang, J. Pang, L. Wang, Q. Dong, D. Jin, Z. Chai, Y. Yang, Z. Gu, X. Cai, W. Ye, L. Kong, X. Qiu, L. Ying, T.C. Chan, Y.L. Shiue, C.F. Li, K. Balamurugan, J.M. Wang, H.H. Tsai, S. Sharan, M. Anver, R. Leighty, E. Sterneck, Y. Zhang, L. Li, F. Chu, H. Wu, X. Xiao, J. Ye, K. Li, A. Subramanian, P. Tamayo, V.K. Mootha, S. Mukherjee, B.L. Ebert, M.A. Gillette, A. Paulovich, S.L. Pomeroy, T.R. Golub, E.S. Lander, C.M. Lindgren, K.F. Eriksson, S. Sihag, J. Lehar, P. Puigserver, E. Carlsson, M. Ridderstrale, E. Laurila, M. Maslowska, H.W. Wang, K. Cianflone, S. Mizuno, R. Seishima, J. Yamasaki, K. Hattori, M. Ogiri, S. Matsui, K. Shigeta, K. Okabayashi, O. Nagano, P. Bajwa, K. Kordylewicz, A. Bilecz, R.R. Lastra, K. Wroblewski, Y. Rinkevich, E. Lengyel, H.A. Kenny, S. Xiao, W. Nai-Dong, Y. Jin-Xiang, T. Long, L. Xiu-Rong, G. Hong, Y. Jie-Cheng, Z. Fei, C. Zhou, L.H. Lyu, H.K. Miao, T. Bahr, Q.Y. Zhang, T. Liang, H.B. Zhou, G.R. Chen, Y. Bai, P.C. Hart, M. Mao, A.L. de Abreu, K. Ansenberger-Fricano, D.N. Ekoue, D. Ganini, A. Kajdacsy-Balla, A.M. Diamond, R.D. Minshall, M.E. Consolaro, M. Shimizu, N. Tanaka, S. Dagdeviren, R.T. Lee, N. Wu, N. Qayyum, M. Haseeb, M.S. Kim, S. Choi, E. Yoshihara, N.M. Alhawiti, S. Al Mahri, M.A. Aziz, S.S. Malik, S. Mohammad, S.Y. Hong, F.X. Yu, Y. Luo, T. Hagen, L. Shen, J.M. O’Shea, M.R. Kaadige, S. Cunha, B.R. Wilde, A.L. Cohen, A.L. Welm, D.E. Ayer, L. Feng, R. Ding, X. Qu, Y. Li, T. Shen, R. Li, J. Zhang, Y. Ru, X. Bu, Q. Yan, L. Gong, H. Xu, B. Liu, X. Fang, D. Yu, T. Wei, Y. Wang, Y. Liang, H. Wang, B. Chen, Q. Mao, W. Xia, T. Zhang, X. Song, Z. Zhang, L. Xu, G. Dong, Y. Chen, J. Ning, W. Cao, T. Du, J. Jiang, X. Feng, B. Zhang, B. Kalyanaraman, G. Cheng, M. Hardy, M. You, T.M. Ashton, W.G. McKenna, L.A. Kunz-Schughart, G.S. Higgins, L. Liu, P.K. Patnana, X. Xie, D. Frank, S.C. Nimmagadda, A. Rosemann, M. Liebmann, L. Klotz, B. Opalka, C. Khandanpour, N. Chen, Y.S. Zhou, L.C. Wang, J.B. Huang, Z. Wu, W. Wang, L. Wei, A.M. Stevens, E.S. Schafer, M. Terrell, R. Rashid, H. Paek, M.B. Bernhardt, A. Weisnicht, W.T. Smith, N.J. Keogh, A. Kapur, P. Mehta, A.D. Simmons, S.S. Ericksen, G. Mehta, S.P. Palecek, M. Felder, Z. Stenerson, A. Nayak, J.M.A. Dominguez, H. Dykstra, C. LaRose, C. Fisk, A. Waldhart, X. Meng, G. Zhao, A.N. Waldhart, A.S. Peck, E.A. Boguslawski, Z.B. Madaj, J. Wen, K. Veldkamp, M. Hollowell, B. Zheng, L.C. Cantley, A. Shaywitz, Y. Dagon, C. Tower, G. Bellinger, C.H. Shen, J. Asara, T.E. McGraw, S.J. Qualls-Histed, C.P. Nielsen, J.A. MacGurn, S. Kim, J. Ge, D. Kim, J.J. Lee, Y.J. Choi, W. Chen, J.W. Bowman, S.S. Foo, L.C. Chang, Q. Liang, M. Pliszka, L. Szablewski, P.B. Ancey, C. Contat, E. Meylan, M.H. Chan, Y.F. Yang, C.H. Li, M. Hsiao, P. Patwari, W.A. Chutkow, K. Cummings, V.L. Verstraeten, J. Lammerding, E.R. Schreiter, J. Deng, T. Pan, Z. Liu, C. McCarthy, J.M. Vicencio, L. Cao, G. Alfano, A.A. Suwaidan, M. Yin, R. Beatson, H. Gong, P. Zhang, X. Hu Show less
We have designed cell-penetrating peptides that target the leucine zipper transcription factors ATF5, CEBPB and CEBPD and that promote apoptotic death of a wide range of cancer cell types, but not nor Show more
We have designed cell-penetrating peptides that target the leucine zipper transcription factors ATF5, CEBPB and CEBPD and that promote apoptotic death of a wide range of cancer cell types, but not normal cells, in vitro and in vivo. Though such peptides have the potential for clinical application, their mechanisms of action are not fully understood. Here, we show that one such peptide, Dpep, compromises glucose uptake and glycolysis in a cell context-dependent manner (in about two-thirds of cancer lines assessed). These actions are dependent on induction of tumor suppressor TXNIP (thioredoxin-interacting protein) mRNA and protein. Knockdown studies show that TXNIP significantly contributes to apoptotic death in those cancer cells in which it is induced by Dpep. The metabolic actions of Dpep on glycolysis led us to explore combinations of Dpep with clinically approved drugs metformin and atovaquone that inhibit oxidative phosphorylation and that are in trials for cancer treatment. Dpep showed additive to synergistic activities in all lines tested. In summary, we find that Dpep induces TXNIP in a cell context-dependent manner that in turn suppresses glucose uptake and glycolysis and contributes to apoptotic death of a range of cancer cells. Show less
📄 PDF DOI: 10.3390/cells13121025
amino-acid
TA Kalyanaraman, N Daver, M Mahendra +242 more · 2023 · Expert opinion on therapeutic targets · Taylor & Francis · added 2026-04-20
TA Kalyanaraman, N Daver, M Mahendra, X Zhang, CV Dang, TM Ashton, WG McKenna, LA Kunz-Schughart, Y Xu, D Xue, A Bankhead, M Huang, CR Myers, Y Wang, B Kalyanaraman, SK Biswas, RAJ Smith, CM Porteous, AM Gane, MP Murphy, RC Hartley, E Fokas, M Benej, X Hong, S Vibhute, M Nishida, N Yamashita, T Ogawa, K Chandran, D Aggarwal, RQ Migrino, D Graham, NN Huynh, CA Hamilton, T Capeloa, J Krzystyniak, D d’Hose, JA Van de Velde, AC Rodriguez, NG Yoon, H Lee, SY Kim, S Yoshida, S Tsutsumi, G Muhlebach, A Rasola, L Neckers, D Picard, G Cheng, H Karoui, M Hardy, F Weinberg, R Hamanaka, WW Wheaton, B Fink, L Coppey, E Davidson, EM Gottwald, M Duss, M Bugarski, J Pan, Y Lee, JR Molina, Y Sun, M Protopopova, J Zielonka, M AbuEid, DM McAllister, L McOlash, IK Srivastava, H Rottenberg, AB Vaidya, PD Radloff, J Philipps, M Nkeyi, W Hughes, G Leoung, F Kramer, CD Freeman, NE Klutman, KC Lamp, A Darade, S Pathak, S Sharma, R Dixon, AL Pozniak, HM Watt, GL Nixon, DM Moss, AE Shone, M Fry, M Pudney, MW Mather, E Darrouzet, M Valkova-Valchanova, M Fiorillo, R Lamb, HB Tanowitz, M Xiang, H Kim, VT Ho, N Gupta, SK Srivastava, S Tian, H Chen, W Tan, D Xiong, P Topchyan, RM Loftus, DK Finlay, G Andrejeva, JC Rathmell, X Li, M Wenes, P Romero, T Gaber, C Strehl, F Buttgereit, A Tasdogan, JM Ubellacker, SJ Morrison, B Faubert, V Ramesh, Q Zhang, LP Burton, G Deng, CD Yanes, SR Lord, AL Harris, ME McGuinness, RL Talbert, H Zhao, KD Swanson, B Zheng, L Di Magno, S Manni, F Di Pastena, SR Veiga, X Ge, CA Mercer, R Masoud, G Reyes-Castellanos, S Lac, F Janku, SH Beom, YW Moon, O Ouari, KA Boyle, J Van Wickle, RB Hill, RF Keyes, D McAllister, Z Bielcikova, J Stursa, L Krizova, K Rohlenova, K Sachaphibulkij, KER Hollinshead, SJ Parker, VV Eapen, S Stemberkova-Hubackova, R Zobalova, M Dubisova, CA Reddy, V Somepalli, T Golakoti, S Jayakumar, RS Patwardhan, D Pal, A Mattarei, M Romio, A Managò, RK Pathak, S Marrache, DA Harn, DR Boulware, MF Pullen, AS Bangdiwala, S Crunkhorn, LD Zorova, VA Popkov, EY Plotnikov, J Joseph, A Sikora, L Dong, J Neuzil, A Solmonson, RJ DeBerardinis, V Gouirand, F Guillaumond, S Vasseur, GM Fischer, A Jalali, DA Kircher, VS LeBleu, JT O’Connell, KN Gonzalez Herrera, JH Park, S Vithayathil, S Kumar, F Sotgia, D Whitaker-Menezes, UE Martinez-Outschoorn, CR Bartman, DR Weilandt, Y Shen, YG Najjar, AV Menk, C Sander, AR Jaiswal, AJ Liu, S Pudakalakatti, MJ McManus, JL Franklin, RA Smith, B Mathieu, L Mignion, M Skwarski, DR McGowan, E Belcher, M Zielonka, B Dranka, HR Bridges, JG Fedor, JN Blaza, A Naguib, G Mathew, CR Reczek, SE Weinberg, BD Singer, EM Steinert, Z Zhao, Y Mei, Z Wang, K Vasan, M Werner, NS Chandel, EM De Francesco, B Ózsvári, S Izreig, A Gariepy, I Kaymak, D Kolb, N Kolishetti, B Surnar Show less
Introduction: Drugs targeting mitochondria are emerging as promising antitumor therapeutics in preclinical models. However, a few of these drugs have shown clinical toxicity. Developing mitochondria- Show more
Introduction: Drugs targeting mitochondria are emerging as promising antitumor therapeutics in preclinical models. However, a few of these drugs have shown clinical toxicity. Developing mitochondria-targeted modified natural compounds and US FDA-approved drugs with increased therapeutic index in cancer is discussed as an alternative strategy. Areas Covered: Triphenylphosphonium cation (TPP + )-based drugs selectively accumulate in the mitochondria of cancer cells due to their increased negative membrane potential, target the oxidative phosphorylation proteins, inhibit mitochondrial respiration, and inhibit tumor proliferation. TPP + -based drugs exert minimal toxic side effects in rodents and humans. These drugs can sensitize radiation and immunotherapies. Expert Opinion: TPP + -based drugs targeting the tumor mitochondrial electron transport chain are a new class of oxidative phosphorylation inhibitors with varying antiproliferative and antimetastatic potencies. Some of these TPP + -based agents, which are synthesized from naturally occurring molecules and FDA-approved drugs, have been tested in mice and did not show notable toxicity, including neurotoxicity, when used at doses under the maximally tolerated dose. Thus, more effort should be directed toward the clinical translation of TPP + -based OXPHOS-inhibiting drugs in cancer prevention and treatment. Show less
no PDF DOI: 10.1080/14728222.2023.2261631
anticancer mitochondria synthesis
S. Trapotsi, G. Drakakis, A. Koutsoukas +1688 more · 2022 · RSC Chemical Biology · Royal Society of Chemistry · added 2026-04-20
S. Trapotsi, G. Drakakis, A. Koutsoukas, I. Cortes–Ciriano, P. Martínez–Alonso, T. E. Malliavin, A. Velazquez-Campoy, S. C. Brewerton, M. J. Bodkin, D. A. Evans, R. C. Glen, J. A. Carrodeguas, A. Bender, S. W. Page, J. E. Maddison, M. R. Trusheim, E. R. Berndt, F. L. Douglas, L. Rovin, C. J. Bailey, G. Zhou, R. Myers, Y. Li, Y. Chen, X. Shen, J. Fenyk-Melody, M. Wu, J. Ventre, T. Doebber, N. Fujii, N. Musi, M. F. Hirshman, L. J. Goodyear, D. E. Moller, I. Bezprozvanny, J. Wu, Q. Li, A. C. Lai, C. M. Crews, J. Downward, F. Ardito, M. Giuliani, D. Perrone, G. Troiano, L. L. Muzio, H. Lodish, A. Berk, S. L. Zipursky, P. Matsudaira, D. Baltimore, J. Darnell, N. Ammeux, B. E. Housden, A. Georgiadis, Y. Hu, N. Perrimon, J. E. Dumont, S. Dremier, I. Pirson, C. Maenhaut, T. Vu, F. X. Claret, H. S. Camp, O. Li, S. C. Wise, Y. H. Hong, C. L. Frankowski, R. Vanbogelen, T. Leff, K. Kores, J. Konc, U. Bren, M.-A. Trapotsi, L. H. Mervin, A. M. Afzal, N. Sturm, O. Engkvist, I. P. Barrett, B. Baillif, J. Wichard, O. Méndez-Lucio, D. Rouquié, J. Inglese, D. S. Auld, B. A. Wetmore, J. F. Wambaugh, S. S. Ferguson, M. A. Sochaski, D. M. Rotroff, K. Freeman, H. J. Clewell III, D. J. Dix, M. E. Andersen, K. A. Houck, B. Allen, R. S. Judson, R. Singh, R. J. Kavlock, A. M. Richard, R. S. Thomas, M. Schenone, V. Dančík, B. K. Wagner, P. A. Clemons, A. Subramanian, R. Narayan, S. M. Corsello, D. D. Peck, T. E. Natoli, X. Lu, J. Gould, J. F. Davis, A. A. Tubelli, J. K. Asiedu, D. L. Lahr, J. E. Hirschman, Z. Liu, M. Donahue, B. Julian, M. Khan, D. Wadden, I. C. Smith, D. Lam, A. Liberzon, C. Toder, M. Bagul, M. Orzechowski, O. M. Enache, F. Piccioni, S. A. Johnson, N. J. Lyons, A. H. Berger, A. F. Shamji, A. N. Brooks, A. Vrcic, C. Flynn, J. Rosains, D. Y. Takeda, R. Hu, D. Davison, J. Lamb, K. Ardlie, L. Hogstrom, P. Greenside, N. S. Gray, S. Silver, X. Wu, W.-N. Zhao, W. Read-Button, S. J. Haggarty, L. V. Ronco, J. S. Boehm, S. L. Schreiber, J. G. Doench, J. A. Bittker, D. E. 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J. Myers, M. Medo, D. M. Aebersold, M. Medová, C. H. Johnson, F. J. Gonzalez, T. Ramirez, M. Daneshian, H. Kamp, F. Y. Bois, M. R. Clench, M. Coen, B. Donley, S. M. Fischer, D. R. Ekman, E. Fabian, C. Guillou, J. Heuer, H. T. Hogberg, H. Jungnickel, H. C. Keun, G. Krennrich, E. Krupp, A. Luch, F. Noor, E. Peter, B. Riefke, M. Seymour, N. Skinner, L. Smirnova, E. Verheij, S. Wagner, T. Hartung, B. van Ravenzwaay, M. Leist, A. M. D. Livera, M. Sysi-Aho, L. Jacob, J. A. Gagnon-Bartsch, S. Castillo, J. A. Simpson, T. P. Speed, R. Chaleckis, I. Meister, P. Zhang, C. E. Wheelock, J. G. Abelin, J. Patel, C. M. Feeney, L. Fagbami, A. L. Creech, L. Pino, J. W. Qiao, E. Kuhn, A. Officer, J. Li, S. Abbatiello, R. Sidman, E. Snyder, S. A. Carr, J. D. Jaffe, Y. A. Chen, S. A. Eschrich, L. Litichevskiy, R. Peckner, C. M. Dunning, J. D. Egertson, S. Egri, T. Ko, B. X. MacLean, A. E. Mungenast, M. Papanastasiou, V. Sharma, J. Z. Young, M. J. MacCoss, L.-H. Tsai, R. Lewis, Z. Tanoli, U. Seemab, A. 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William, U. Sarkans, A. Brazma, D. L. Svoboda, T. Saddler, Y. Igarashi, N. Nakatsu, T. Yamashita, A. Ono, Y. Ohno, T. Urushidani, H. Yamada, N. Lim, P. Pavlidis, A. Musa, L. S. Ghoraie, S.-D. Zhang, G. Galzko, O. Yli-Harja, M. Dehmer, B. Haibe-Kains, F. Emmert-Streib, M. Bickle, S. Seal, H. Yang, L. Vollmers, T. R. Jones, M. R. Lamprecht, C. Clarke, I. H. Kang, O. Friman, D. A. Guertin, J. H. Chang, R. A. Lindquist, J. Moffat, P. Golland, D. M. Sabatini, M. Held, M. H. A. Schmitz, B. Fischer, T. Walter, B. Neumann, M. H. Olma, M. Peter, J. Ellenberg, D. W. Gerlich, S. Rajaram, B. Pavie, L. F. Wu, S. J. Altschuler, J. Ollion, J. Cochennec, F. Loll, C. Escudé, T. Boudier, T. Wollmann, M. Gunkel, I. Chung, H. Erfle, K. Rippe, K. Rohr, J. C. Caicedo, A. Goodman, K. W. Karhohs, B. A. Cimini, J. Ackerman, M. Haghighi, C. Heng, T. Becker, M. Doan, C. McQuin, M. Rohban, V. Chernyshev, L. Kamentsky, L. Ding, S. M. Rafelski, D. Thirstrup, W. Wiegraebe, F. Heigwer, S. Warchal, P. Qiu, C. 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Ternent, J. A. Vizcaíno, P. Samaras, T. Schmidt, M. Frejno, S. Gessulat, M. Reinecke, A. Jarzab, J. Zecha, J. Mergner, P. Giansanti, H.-C. Ehrlich, S. Aiche, J. Rank, H. Kienegger, H. Krcmar, B. Kuster, M. Wilhelm, B. Aslam, M. Basit, M. A. Nisar, M. Khurshid, M. H. Rasool, Y. Lao, X. Wang, N. Xu, H. Zhang, H. Xu, K. Hollywood, D. R. Brison, R. Goodacre, L. Zhang, C. Ma, H. Chao, Y. Long, Z. Li, X. Ge, H. Xia, Y. Yin, J. Batley, M. Li, R. Cavill, D. Jennen, J. Kleinjans, J. J. Briedé, W. Lu, X. Su, M. S. Klein, I. A. Lewis, O. Fiehn, J. D. Rabinowitz, M. Wright Muelas, I. Roberts, F. Mughal, S. O’Hagan, P. J. Day, D. B. Kell, Y. Lin, G. W. Caldwell, W. Lang, J. Masucci, K. Peters, J. Bradbury, S. Bergmann, M. Capuccini, M. Cascante, P. de Atauri, T. M. D. Ebbels, C. Foguet, R. Glen, A. Gonzalez-Beltran, U. L. Günther, E. Handakas, T. Hankemeier, K. Haug, S. Herman, P. Holub, M. Izzo, D. Jacob, D. Johnson, F. Jourdan, N. Kale, I. Karaman, B. Khalili, P. Emami Khonsari, K. Kultima, S. 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Mäkelä, T. Aittokallio, M. Iwata, R. Sawada, H. Iwata, M. Kotera, Y. Yamanishi, E. Dazert, M. Colombi, T. Boldanova, S. Moes, D. Adametz, L. Quagliata, V. Roth, L. Terracciano, M. H. Heim, P. Jenoe, M. N. Hall, D. Carrella, F. Napolitano, R. Rispoli, M. Miglietta, A. Carissimo, L. Cutillo, F. Sirci, F. Gregoretti, D. Di Bernardo, A. Conesa, S. Beck Show less
The elucidation of a compound's Mechanism of Action (MoA) is a challenging task in the drug discovery process, but it is important in order to rationalise phenotypic findings and to anticipate potenti Show more
The elucidation of a compound's Mechanism of Action (MoA) is a challenging task in the drug discovery process, but it is important in order to rationalise phenotypic findings and to anticipate potential side-effects. Bioinformatic approaches, advances in machine learning techniques and the increasing deposition of high-throughput data in public databases have significantly contributed to recent advances in the field, but it is not straightforward to decide which data and methods are most suitable to use in a given case. In this review, we focus on these methods and data and their applications in generating MoA hypotheses for subsequent experimental validation. We discuss compound-specific data such as -omics, cell morphology and bioactivity data, as well as commonly used supplementary prior knowledge such as network and pathway data, and provide information on databases where this data can be accessed. In terms of methodologies, we discuss both well-established methods (connectivity mapping, pathway enrichment) as well as more developing methods (neural networks and multi-omics integration). Finally, we review case studies where the MoA of a compound was successfully suggested from computational analysis by incorporating multiple data modalities and/or methodologies. Our aim for this review is to provide researchers with insights into the benefits and drawbacks of both the data and methods in terms of level of understanding, biases and interpretation – and to highlight future avenues of investigation which we foresee will improve the field of MoA elucidation, including greater public access to -omics data and methodologies which are capable of data integration. Show less
📄 PDF DOI: 10.1039/d1cb00069a
ML review
JP Ježek, AGW Leslie, R Lutter +1993 more · 2018 · Antioxidants & redox signaling · added 2026-04-20
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Hou, Y Ding, T Zhang, C Shi, W Fu, Z Cai, F Yin, H Sancheti, E Cadenas, H Yoshitomi, K Yamazaki, I Tanaka, T Liu, SB Jin, C Ning, U Lendahl, M Nistér, SX Yu, CT Du, W Chen, QQ Lei, N Li, S Qi, XJ Zhang, GQ Hu, XM Deng, WY Han, YJ Yang, XX Yu, W Mao, A Zhong, P Schow, J Brush, SW Sherwood, G Pan, P Perret, O Peroni, YB Kim, XX Zheng, R Shen, CT Lin, JA Porco, HJ Zhang, W Zhao, S Venkataraman, MEC Robbins, GR Buettner, KC Kregel, LW Oberley, I Khvorostov, JS Hong, Y Oktay, L Vergnes, E Nuebel, PN Wahjudi, K Setoguchi, A Do, HJ Jung, JM McCaffery, IJ Kurland, K Reue, WNP Lee, CM Koehler, MA Teitell, K Zhang, Z Song, G Zheng, J Lyu, S Liu, J Huang, C Liu, D Xiang, M Xie, Q Zeng, M Zhou, PKH Tam, KSL Lam, B Huang, Y Liang, D Wu, Y Zhou, T Cai, J Xu, L Jiang, J Wu, Q Sun, R Zhu, A Ebner, T Haselgrübler, HJ Gruber, P Hinterdorfer Show less
Abstract Significance: Mitochondria are the energetic, metabolic, redox, and information signaling centers of the cell. Substrate pressure, mitochondrial network dynamics, and cristae morphology Show more
Abstract Significance: Mitochondria are the energetic, metabolic, redox, and information signaling centers of the cell. Substrate pressure, mitochondrial network dynamics, and cristae morphology state are integrated by the protonmotive force Δ p or its potential component, Δ Ψ , which are attenuated by proton backflux into the matrix, termed uncoupling. The mitochondrial uncoupling proteins (UCP1–5) play an eminent role in the regulation of each of the mentioned aspects, being involved in numerous physiological events including redox signaling. Recent Advances: UCP2 structure, including purine nucleotide and fatty acid (FA) binding sites, strongly support the FA cycling mechanism: UCP2 expels FA anions, whereas uncoupling is achieved by the membrane backflux of protonated FA. Nascent FAs, cleaved by phospholipases, are preferential. The resulting Δ p dissipation decreases superoxide formation dependent on Δ p . UCP-mediated antioxidant protection and its impairment are expected to play a major role in cell physiology and pathology. Moreover, UCP2-mediated aspartate, oxaloacetate, and malate antiport with phosphate is expected to alter metabolism of cancer cells. Critical Issues: A wide range of UCP antioxidant effects and participations in redox signaling have been reported; however, mechanisms of UCP activation are still debated. Switching off/on the UCP2 protonophoretic function might serve as redox signaling either by employing/releasing the extra capacity of cell antioxidant systems or by directly increasing/decreasing mitochondrial superoxide sources. Rapid UCP2 degradation, FA levels, elevation of purine nucleotides, decreased Mg 2+ , or increased pyruvate accumulation may initiate UCP-mediated redox signaling. Future Directions: Issues such as UCP2 participation in glucose sensing, neuronal (synaptic) function, and immune cell activation should be elucidated. Antioxid. Redox Signal. 29, 667–714. Show less
📄 PDF DOI: 10.1089/ars.2017.7225
mitochondria