Direct Activation of Bax Protein for Cancer Therapy

Zhiqing Liu, Ye Ding, Na Ye, Christopher Wild, Haiying Chen, Jia Zhou

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

Bax, a central cell death regulator, is an indispensable gateway to mitochondrial dysfunction and a major proapoptotic member of the B-cell lymphoma 2 (Bcl-2) family proteins that control apoptosis in normal and cancer cells. Dysfunction of apoptosis renders the cancer cell resistant to treatment as well as promotes tumorigenesis. Bax activation induces mitochondrial membrane permeabilization, thereby leading to the release of apoptotic factor cytochrome c and consequently cancer cell death. A number of drugs in clinical use are known to indirectly activate Bax. Intriguingly, recent efforts demonstrate that Bax can serve as a promising direct target for small-molecule drug discovery. Several direct Bax activators have been identified to hold promise for cancer therapy with the advantages of specificity and the potential of overcoming chemo- and radioresistance. Further investigation of this new class of drug candidates will be needed to advance them into the clinic as a novel means to treat cancer.

Original languageEnglish (US)
Pages (from-to)313-341
Number of pages29
JournalMedicinal Research Reviews
Volume36
Issue number2
DOIs
StatePublished - Mar 1 2016

Fingerprint

bcl-2-Associated X Protein
Neoplasms
Cell Death
Apoptosis
Therapeutics
Mitochondrial Membranes
B-Cell Lymphoma
Drug Discovery
Cytochromes c
Pharmaceutical Preparations
Carcinogenesis
Proteins

Keywords

  • Apoptosis
  • Bax activators
  • Bcl-2 family proteins
  • Cancer therapy
  • Drug discovery

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery
  • Pharmacology

Cite this

Direct Activation of Bax Protein for Cancer Therapy. / Liu, Zhiqing; Ding, Ye; Ye, Na; Wild, Christopher; Chen, Haiying; Zhou, Jia.

In: Medicinal Research Reviews, Vol. 36, No. 2, 01.03.2016, p. 313-341.

Research output: Contribution to journalArticle

Liu, Z, Ding, Y, Ye, N, Wild, C, Chen, H & Zhou, J 2016, 'Direct Activation of Bax Protein for Cancer Therapy', Medicinal Research Reviews, vol. 36, no. 2, pp. 313-341. https://doi.org/10.1002/med.21379
Liu, Zhiqing ; Ding, Ye ; Ye, Na ; Wild, Christopher ; Chen, Haiying ; Zhou, Jia. / Direct Activation of Bax Protein for Cancer Therapy. In: Medicinal Research Reviews. 2016 ; Vol. 36, No. 2. pp. 313-341.
@article{d8c00eae3bd9429387c8fe68b8a83fa5,
title = "Direct Activation of Bax Protein for Cancer Therapy",
abstract = "Bax, a central cell death regulator, is an indispensable gateway to mitochondrial dysfunction and a major proapoptotic member of the B-cell lymphoma 2 (Bcl-2) family proteins that control apoptosis in normal and cancer cells. Dysfunction of apoptosis renders the cancer cell resistant to treatment as well as promotes tumorigenesis. Bax activation induces mitochondrial membrane permeabilization, thereby leading to the release of apoptotic factor cytochrome c and consequently cancer cell death. A number of drugs in clinical use are known to indirectly activate Bax. Intriguingly, recent efforts demonstrate that Bax can serve as a promising direct target for small-molecule drug discovery. Several direct Bax activators have been identified to hold promise for cancer therapy with the advantages of specificity and the potential of overcoming chemo- and radioresistance. Further investigation of this new class of drug candidates will be needed to advance them into the clinic as a novel means to treat cancer.",
keywords = "Apoptosis, Bax activators, Bcl-2 family proteins, Cancer therapy, Drug discovery",
author = "Zhiqing Liu and Ye Ding and Na Ye and Christopher Wild and Haiying Chen and Jia Zhou",
year = "2016",
month = "3",
day = "1",
doi = "10.1002/med.21379",
language = "English (US)",
volume = "36",
pages = "313--341",
journal = "Medicinal Research Reviews",
issn = "0198-6325",
publisher = "John Wiley and Sons Inc.",
number = "2",

}

TY - JOUR

T1 - Direct Activation of Bax Protein for Cancer Therapy

AU - Liu, Zhiqing

AU - Ding, Ye

AU - Ye, Na

AU - Wild, Christopher

AU - Chen, Haiying

AU - Zhou, Jia

PY - 2016/3/1

Y1 - 2016/3/1

N2 - Bax, a central cell death regulator, is an indispensable gateway to mitochondrial dysfunction and a major proapoptotic member of the B-cell lymphoma 2 (Bcl-2) family proteins that control apoptosis in normal and cancer cells. Dysfunction of apoptosis renders the cancer cell resistant to treatment as well as promotes tumorigenesis. Bax activation induces mitochondrial membrane permeabilization, thereby leading to the release of apoptotic factor cytochrome c and consequently cancer cell death. A number of drugs in clinical use are known to indirectly activate Bax. Intriguingly, recent efforts demonstrate that Bax can serve as a promising direct target for small-molecule drug discovery. Several direct Bax activators have been identified to hold promise for cancer therapy with the advantages of specificity and the potential of overcoming chemo- and radioresistance. Further investigation of this new class of drug candidates will be needed to advance them into the clinic as a novel means to treat cancer.

AB - Bax, a central cell death regulator, is an indispensable gateway to mitochondrial dysfunction and a major proapoptotic member of the B-cell lymphoma 2 (Bcl-2) family proteins that control apoptosis in normal and cancer cells. Dysfunction of apoptosis renders the cancer cell resistant to treatment as well as promotes tumorigenesis. Bax activation induces mitochondrial membrane permeabilization, thereby leading to the release of apoptotic factor cytochrome c and consequently cancer cell death. A number of drugs in clinical use are known to indirectly activate Bax. Intriguingly, recent efforts demonstrate that Bax can serve as a promising direct target for small-molecule drug discovery. Several direct Bax activators have been identified to hold promise for cancer therapy with the advantages of specificity and the potential of overcoming chemo- and radioresistance. Further investigation of this new class of drug candidates will be needed to advance them into the clinic as a novel means to treat cancer.

KW - Apoptosis

KW - Bax activators

KW - Bcl-2 family proteins

KW - Cancer therapy

KW - Drug discovery

UR - http://www.scopus.com/inward/record.url?scp=84958900764&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84958900764&partnerID=8YFLogxK

U2 - 10.1002/med.21379

DO - 10.1002/med.21379

M3 - Article

C2 - 26395559

AN - SCOPUS:84958900764

VL - 36

SP - 313

EP - 341

JO - Medicinal Research Reviews

JF - Medicinal Research Reviews

SN - 0198-6325

IS - 2

ER -