Statins are potential anticancerous agents (Review)

Abstract

Abstract. Statins are inhibitors of 3-hydroxy-3-methylglutarylcoenzyme A reductase (HMGCR), which is a rate-limiting enzyme in the mevalonate pathway. The pleiotropic effects of statins may be mediated by the inhibition of downstream products such as small GTP-binding proteins, Rho, Ras and Rac whose localization and function are dependent on isoprenylation. Preclinical studies of statins in different cancer cell lines and animal models showed antiproliferative, pro-apoptotic and anti-invasive effects. Notably, statins showed targeted action in cancerous cell lines compared to normal cells. Previous studies have also shown the synergistic effects of statins with chemotherapeutic agents and radiotherapy. This effect of statins was also observed in chemotherapeutic-resistant tumors. Statins were reported to sensitize the cells to radiation by arresting them in the late G1 phase of the cell cycle. Similarly, population-based studies also demonstrated a chemopreventive and survival benefit of statins in various types of cancers. However, this benefit has yet to be proven in clinical trials. The interindividual variation in response to statins may be contributed to many genetic and non-genetic factors, including single-nucleotide polymorphisms in HMGCR gene and the overexpression of heterogeneous nuclear ribonucleoprotein A1, which was reported to reduce HMGCR enzyme activity. However, more studies with large phase III randomized controlled trials in cancer patients should be conducted to establish the effect of statins in cancer prevention and treatment.

Ethanol extract of Zhongtian hawthorn lowers serum cholesterol in mice by inhibiting transcription of 3-hydroxy-3-methylglutaryl-CoA reductase via nuclear factor-kappa B signal pathway

“…33 Therefore, research on the regulation of HMGCR has been remaining the subject of great interest. The sterol regulatory element-binding protein (SREBP) has been considered as the key factor in regulating the transcription of HMGCR.…”

Metabolic networks in ferroptosis (Review)

“…Preclinical studies have demonstrated the pro-apoptotic effects of statins (39,40). Furthermore, human prostate cancer PC3 cells treated with atorvastatin undergo autophagy, whereas simvastatin leads to the induction of apoptosis in HCT116 colorectal cancer cells and renal cell carcinoma cells (41). Statins also downregulate the mevalonate pathway and block the biosynthesis of cellular isoprenoids, including IPP, which are responsible for the post-translational modification of Sec-tRNA [Ser]Sec and the synthesis of GPX4 (6,35,42).…”

The Effect of High-Dose Simvastatin Therapy on Patients with Acute Cerebral Infarction

“…Simvastatin would also inhibit the biosynthesis of isoprenoid intermediates such as geranyl and farnesyl pyrophosphate, and then affect the posttranslational prenylation of several important cellsignaling proteins during immune responses [11]. Therefore, simvastatin has been shown to have antitumor potential in many different cell lines [12][13][14].…”