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Review
. 2022 Aug 12:10:948217.
doi: 10.3389/fchem.2022.948217. eCollection 2022.

Potential of histone deacetylase inhibitors in the control and regulation of prostate, breast and ovarian cancer

Siddhartha Das Pramanik  1 , Amit Kumar Halder  2 , Ushmita Mukherjee  2 , Dharmendra Kumar  3 , Yadu Nandan Dey  2 , Mogana R  4
Affiliations
Review

Potential of histone deacetylase inhibitors in the control and regulation of prostate, breast and ovarian cancer

Siddhartha Das Pramanik et al. Front Chem. .

Abstract

Histone deacetylases (HDACs) are enzymes that play a role in chromatin remodeling and epigenetics. They belong to a specific category of enzymes that eliminate the acetyl part of the histones' -N-acetyl lysine, causing the histones to be wrapped compactly around DNA. Numerous biological processes rely on HDACs, including cell proliferation and differentiation, angiogenesis, metastasis, gene regulation, and transcription. Epigenetic changes, specifically increased expression and activity of HDACs, are commonly detected in cancer. As a result, HDACi could be used to develop anticancer drugs. Although preclinical outcomes with HDACs as monotherapy have been promising clinical trials have had mixed results and limited success. In both preclinical and clinical trials, however, combination therapy with different anticancer medicines has proved to have synergistic effects. Furthermore, these combinations improved efficacy, decreased tumor resistance to therapy, and decreased toxicity. In the present review, the detailed modes of action, classification of HDACs, and their correlation with different cancers like prostate, breast, and ovarian cancer were discussed. Further, the different cell signaling pathways and the structure-activity relationship and pharmaco-toxicological properties of the HDACi, and their synergistic effects with other anticancer drugs observed in recent preclinical and clinical studies used in combination therapy were discussed for prostate, breast, and ovarian cancer treatment.

Keywords: HDAC inhibitors (HDACi); Histone deacetylase (HDAC); breast cancer; ovarian cancer; prostate cancer.

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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
Structures of HDACi designed in recent years depicted anti-proliferative potential against the prostate carcinoma cell lines.
FIGURE 2
FIGURE 2
Structures of HDACi designed in recent years that depicted anti-proliferative potential against the breast carcinoma cell lines.
FIGURE 3
FIGURE 3
Targets for combination therapies with HDACi in CRPC. CRPC, castration-resistant prostate cancer; HDACi, Histone deacetylase inhibitors; TRAIL, TNF-related apoptosis-inducing ligand; MEK, MAPK/ERK kinase.
FIGURE 4
FIGURE 4
Role of HDACs in pathogenesis of ovarian cancer.
FIGURE 5
FIGURE 5
Role of HDACi in treatment ovarian cancer. HDAC, Histone deacetylase; HAT, Histone acetyltransferase; HDACi, Histone deacetylase inhibitor.
See this image and copyright information in PMC

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