The Mechanistic Roles of Sirtuins in Breast and Prostate Cancer

Abstract

Mammalian sirtuins (SIRT1–7) are involved in a myriad of cellular processes, including apoptosis, proliferation, differentiation, epithelial-mesenchymal transition, aging, DNA repair, senescence, viability, survival, and stress response. In this review, we discuss the current information on the mechanistic roles of SIRT1–7 and their downstream effects (tumor promotion or suppression) in cancers of the breast and prostate. Specifically, we highlight the involvement of sirtuins in the regulation of various proteins implicated in proliferation, apoptosis, autophagy, chemoresistance, invasion, migration, and metastasis of breast and prostate cancer. Additionally, we highlight the available information regarding SIRT1–7 regulation by miRNAs, laying much emphasis on the consequences in the progression of breast and prostate cancer.

The Implication of Growth Arrest-Specific 5 rs145204276 Polymorphism and Serum Expression of Sirtuin 1, Transforming Growth Factor-Beta, and microRNA-182 in Breast Cancer

“…Class III histone deacetylase (SIRT-1) plays a role in several biological processes, including DNA repair, cancer, and cell survival and proliferation. 10 This study demonstrated that serum SIRT-1 levels in BC patients were considerably higher than in healthy subjects. Multiple human cancers, including prostate cancer, colon cancer, and hepatocellular carcinoma, have been linked to increased SIRT-1 expression.…”

“… 9 Based on the tumor types’ microenvironment, upstream regulators, and downstream target genes, the function of SIRT-1 is still controversial. 10 Transforming growth factor-beta (TGF-β) is a cytokine that controls how cells behave. It has numerous ways it affects epithelial cells and cell clusters that develop into carcinomas both in vitro and in vivo .…”

Hypophyllanthin and Phyllanthin from Phyllanthus niruri Synergize Doxorubicin Anticancer Properties against Resistant Breast Cancer Cells

“…Herein, we found that hypophyllanthin and phyllanthin treatment alone or in combination with DOX are significantly downregulating the expression of SIRT1 and its downstream activity marker, p-Akt protein, in MCF7 ADR cells, providing a new insight into the potential use of hypophyllanthin and phyllanthin in the treatment of resistant breast cancer phenotype. In addition, SIRT1 signaling is reported to be associated with EMT transcriptional factors in cancer, which in turn enhances cancer cell migration, invasion, and metastasis. , EMT is a biological transformation of epithelial cells to mesenchymal cells through which cellular polarity and connections are lost, which leads to stronger migratory and invasive cancer cell properties. EMT not only promotes metastasis of cancer cells but also enhances the development of DOX resistance .…”

Integrated network pharmacology, bioinformatics, and molecular docking to explore the mechanisms of berberine regulating autophagy in breast cancer

“…[35] SIRT2, a NAD-dependent deacetylase, plays a multifaceted role in breast tumors, with evidence suggesting both oncogenic and tumor-suppressive functions. [36] In the context of cisplatin-induced renal fibrosis, berberine has been found to alleviate fibrotic processes by upregulating DUSP6 while inhibiting P2X7R, p-ERK1/2, MDM2, and SIRT2. [37] Additionally, our docking analysis revealed a particularly strong binding affinity between berberine and SIRT2.…”