Broad targeting of resistance to apoptosis in cancer

Ramzi M. Mohammad, Irfana Muqbil, Leroy Lowe, Clement Yedjou, Hsue Yin Hsu, Liang Tzung Lin, Markus David Siegelin, Carmela Fimognari, Nagi B. Kumar, Q. Ping Dou, Huanjie Yang, Abbas K. Samadi, Gian Luigi Russo, Carmela Spagnuolo, Swapan K. Ray, Mrinmay Chakrabarti, James D. Morre, Helen M. Coley, Kanya Honoki, Hiromasa FujiiAlexandros G. Georgakilas, Amedeo Amedei, Elena Niccolai, Amr Amin, S. Salman Ashraf, William G. Helferich, Xujuan Yang, Chandra S. Boosani, Gunjan Guha, Dipita Bhakta, Maria Rosa Ciriolo, Katia Aquilano, Sophie Chen, Sulma I. Mohammed, W. Nicol Keith, Alan Bilsland, Dorota Halicka, Somaira Nowsheen, Asfar S. Azmi

Research output: Contribution to journalArticle

178 Citations (Scopus)

Abstract

Apoptosis or programmed cell death is natural way of removing aged cells from the body. Most of the anti-cancer therapies trigger apoptosis induction and related cell death networks to eliminate malignant cells. However, in cancer, de-regulated apoptotic signaling, particularly the activation of an anti-apoptotic systems, allows cancer cells to escape this program leading to uncontrolled proliferation resulting in tumor survival, therapeutic resistance and recurrence of cancer. This resistance is a complicated phenomenon that emanates from the interactions of various molecules and signaling pathways. In this comprehensive review we discuss the various factors contributing to apoptosis resistance in cancers. The key resistance targets that are discussed include (1) Bcl-2 and Mcl-1 proteins; (2) autophagy processes; (3) necrosis and necroptosis; (4) heat shock protein signaling; (5) the proteasome pathway; (6) epigenetic mechanisms; and (7) aberrant nuclear export signaling. The shortcomings of current therapeutic modalities are highlighted and a broad spectrum strategy using approaches including (a) gossypol; (b) epigallocatechin-3-gallate; (c) UMI-77 (d) triptolide and (e) selinexor that can be used to overcome cell death resistance is presented. This review provides a roadmap for the design of successful anti-cancer strategies that overcome resistance to apoptosis for better therapeutic outcome in patients with cancer.

Original languageEnglish
JournalSeminars in Cancer Biology
DOIs
Publication statusAccepted/In press - 2015

Fingerprint

Apoptosis
Neoplasms
Cell Death
Gossypol
Cell Nucleus Active Transport
Autophagy
Proteasome Endopeptidase Complex
Therapeutics
Heat-Shock Proteins
Epigenomics
Necrosis
Recurrence
Survival
Proteins

Keywords

  • Apoptosis
  • Apoptosis evasion
  • Autophagy
  • Necrosis
  • Nuclear transporters, natural chemopreventive agents

ASJC Scopus subject areas

  • Cancer Research

Cite this

Mohammad, R. M., Muqbil, I., Lowe, L., Yedjou, C., Hsu, H. Y., Lin, L. T., ... Azmi, A. S. (Accepted/In press). Broad targeting of resistance to apoptosis in cancer. Seminars in Cancer Biology. https://doi.org/10.1016/j.semcancer.2015.03.001

Broad targeting of resistance to apoptosis in cancer. / Mohammad, Ramzi M.; Muqbil, Irfana; Lowe, Leroy; Yedjou, Clement; Hsu, Hsue Yin; Lin, Liang Tzung; Siegelin, Markus David; Fimognari, Carmela; Kumar, Nagi B.; Dou, Q. Ping; Yang, Huanjie; Samadi, Abbas K.; Russo, Gian Luigi; Spagnuolo, Carmela; Ray, Swapan K.; Chakrabarti, Mrinmay; Morre, James D.; Coley, Helen M.; Honoki, Kanya; Fujii, Hiromasa; Georgakilas, Alexandros G.; Amedei, Amedeo; Niccolai, Elena; Amin, Amr; Ashraf, S. Salman; Helferich, William G.; Yang, Xujuan; Boosani, Chandra S.; Guha, Gunjan; Bhakta, Dipita; Ciriolo, Maria Rosa; Aquilano, Katia; Chen, Sophie; Mohammed, Sulma I.; Keith, W. Nicol; Bilsland, Alan; Halicka, Dorota; Nowsheen, Somaira; Azmi, Asfar S.

In: Seminars in Cancer Biology, 2015.

Research output: Contribution to journalArticle

Mohammad, RM, Muqbil, I, Lowe, L, Yedjou, C, Hsu, HY, Lin, LT, Siegelin, MD, Fimognari, C, Kumar, NB, Dou, QP, Yang, H, Samadi, AK, Russo, GL, Spagnuolo, C, Ray, SK, Chakrabarti, M, Morre, JD, Coley, HM, Honoki, K, Fujii, H, Georgakilas, AG, Amedei, A, Niccolai, E, Amin, A, Ashraf, SS, Helferich, WG, Yang, X, Boosani, CS, Guha, G, Bhakta, D, Ciriolo, MR, Aquilano, K, Chen, S, Mohammed, SI, Keith, WN, Bilsland, A, Halicka, D, Nowsheen, S & Azmi, AS 2015, 'Broad targeting of resistance to apoptosis in cancer', Seminars in Cancer Biology. https://doi.org/10.1016/j.semcancer.2015.03.001
Mohammad, Ramzi M. ; Muqbil, Irfana ; Lowe, Leroy ; Yedjou, Clement ; Hsu, Hsue Yin ; Lin, Liang Tzung ; Siegelin, Markus David ; Fimognari, Carmela ; Kumar, Nagi B. ; Dou, Q. Ping ; Yang, Huanjie ; Samadi, Abbas K. ; Russo, Gian Luigi ; Spagnuolo, Carmela ; Ray, Swapan K. ; Chakrabarti, Mrinmay ; Morre, James D. ; Coley, Helen M. ; Honoki, Kanya ; Fujii, Hiromasa ; Georgakilas, Alexandros G. ; Amedei, Amedeo ; Niccolai, Elena ; Amin, Amr ; Ashraf, S. Salman ; Helferich, William G. ; Yang, Xujuan ; Boosani, Chandra S. ; Guha, Gunjan ; Bhakta, Dipita ; Ciriolo, Maria Rosa ; Aquilano, Katia ; Chen, Sophie ; Mohammed, Sulma I. ; Keith, W. Nicol ; Bilsland, Alan ; Halicka, Dorota ; Nowsheen, Somaira ; Azmi, Asfar S. / Broad targeting of resistance to apoptosis in cancer. In: Seminars in Cancer Biology. 2015.
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abstract = "Apoptosis or programmed cell death is natural way of removing aged cells from the body. Most of the anti-cancer therapies trigger apoptosis induction and related cell death networks to eliminate malignant cells. However, in cancer, de-regulated apoptotic signaling, particularly the activation of an anti-apoptotic systems, allows cancer cells to escape this program leading to uncontrolled proliferation resulting in tumor survival, therapeutic resistance and recurrence of cancer. This resistance is a complicated phenomenon that emanates from the interactions of various molecules and signaling pathways. In this comprehensive review we discuss the various factors contributing to apoptosis resistance in cancers. The key resistance targets that are discussed include (1) Bcl-2 and Mcl-1 proteins; (2) autophagy processes; (3) necrosis and necroptosis; (4) heat shock protein signaling; (5) the proteasome pathway; (6) epigenetic mechanisms; and (7) aberrant nuclear export signaling. The shortcomings of current therapeutic modalities are highlighted and a broad spectrum strategy using approaches including (a) gossypol; (b) epigallocatechin-3-gallate; (c) UMI-77 (d) triptolide and (e) selinexor that can be used to overcome cell death resistance is presented. This review provides a roadmap for the design of successful anti-cancer strategies that overcome resistance to apoptosis for better therapeutic outcome in patients with cancer.",
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AU - Muqbil, Irfana

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AU - Yedjou, Clement

AU - Hsu, Hsue Yin

AU - Lin, Liang Tzung

AU - Siegelin, Markus David

AU - Fimognari, Carmela

AU - Kumar, Nagi B.

AU - Dou, Q. Ping

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AU - Samadi, Abbas K.

AU - Russo, Gian Luigi

AU - Spagnuolo, Carmela

AU - Ray, Swapan K.

AU - Chakrabarti, Mrinmay

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AU - Coley, Helen M.

AU - Honoki, Kanya

AU - Fujii, Hiromasa

AU - Georgakilas, Alexandros G.

AU - Amedei, Amedeo

AU - Niccolai, Elena

AU - Amin, Amr

AU - Ashraf, S. Salman

AU - Helferich, William G.

AU - Yang, Xujuan

AU - Boosani, Chandra S.

AU - Guha, Gunjan

AU - Bhakta, Dipita

AU - Ciriolo, Maria Rosa

AU - Aquilano, Katia

AU - Chen, Sophie

AU - Mohammed, Sulma I.

AU - Keith, W. Nicol

AU - Bilsland, Alan

AU - Halicka, Dorota

AU - Nowsheen, Somaira

AU - Azmi, Asfar S.

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