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Review
. 2022 Oct 12:12:985363.
doi: 10.3389/fonc.2022.985363. eCollection 2022.

The role of BCL-2 family proteins in regulating apoptosis and cancer therapy

Shanna Qian  1 , Zhong Wei  2 , Wanting Yang  1 , Jinling Huang  1 , Yinfeng Yang  3 , Jinghui Wang  1
Affiliations
Review

The role of BCL-2 family proteins in regulating apoptosis and cancer therapy

Shanna Qian et al. Front Oncol. .

Abstract

Apoptosis, as a very important biological process, is a response to developmental cues or cellular stress. Impaired apoptosis plays a central role in the development of cancer and also reduces the efficacy of traditional cytotoxic therapies. Members of the B-cell lymphoma 2 (BCL-2) protein family have pro- or anti-apoptotic activities and have been studied intensively over the past decade for their importance in regulating apoptosis, tumorigenesis, and cellular responses to anticancer therapy. Since the inflammatory response induced by apoptosis-induced cell death is very small, at present, the development of anticancer drugs targeting apoptosis has attracted more and more attention. Consequently, the focus of this review is to summarize the current research on the role of BCL-2 family proteins in regulating apoptosis and the development of drugs targeting BCL-2 anti-apoptotic proteins. Additionally, the mechanism of BCL-2 family proteins in regulating apoptosis was also explored. All the findings indicate the potential of BCL-2 family proteins in the therapy of cancer.

Keywords: Bcl-2; apoptosis; autoimmunity; cancer; systematic.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
The mechanism of BCL-2 family proteins in regulating apoptosis. Driven by BCL-2 family proteins, which are primarily localized to mitochondria and present on the ER, pro-apoptotic family proteins can act directly on the mitochondria to trigger the apoptosis mechanism, and anti-apoptotic proteins need to work together with other proteins to cause apoptosis, release cytochrome C, and activation of caspase of apoptosis.
Figure 2
Figure 2
Expression of BCL-2 in various tumors. Comparisons of BCL-2 expression levels between tumor tissues from TCGA database and normal tissues from the GTEx database (*P < 0.05, **P < 0.01, ***P < 0.001).
Figure 3
Figure 3
Mechanism of BCL-2 drug action. BCL-2 inhibitors interact with members of the BCL2 family of proteins to reduce the production of anti-apoptotic proteins, block the anti-apoptotic defense mechanism of tumor cells, replace and release pro-apoptotic proteins, induce apoptosis, and thus achieve antitumor effects.
Figure 4
Figure 4
Venetoclax mechanism diagram. Venetoclax is a highly selective inhibitor of BCL-2. Highly expressed cancer cells of BCL-2 are spared from apoptosis by inhibiting the activation of BAX and BAK. Venetoclax selectively binds to BCL-2 in the binding tank, directly and indirectly reducing the inhibitory effect on BAX/BAK and initiating apoptosis.
See this image and copyright information in PMC

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