Novel Effects of Statins on Cancer via Autophagy

Abstract

Cancer is one of the main causes of death globally. Most of the molecular mechanisms underlying cancer are marked by complex aberrations that activate the critical cell-signaling pathways that play a pivotal role in cell metabolism, tumor development, cytoskeletal reorganization, and metastasis. The phosphatidylinositol 3-kinase/protein kinase-B/mammalian target of the rapamycin (PI3K/AKT/mTOR) pathway is one of the main signaling pathways involved in carcinogenesis and metastasis. Autophagy, a cellular pathway that delivers cytoplasmic components to lysosomes for degradation, plays a dual role in cancer, as either a tumor promoter or a tumor suppressor, depending on the stage of the carcinogenesis. Statins are the group of drugs of choice to lower the level of low-density lipoprotein (LDL) cholesterol in the blood. Experimental and clinical data suggest the potential of statins in the treatment of cancer. In vitro and in vivo studies have demonstrated the molecular mechanisms through which statins inhibit the proliferation and metastasis of cancer cells in different types of cancer. The anticancer properties of statins have been shown to result in the suppression of tumor growth, the induction of apoptosis, and autophagy. This literature review shows the dual role of the autophagic process in cancer and the latest scientific evidence related to the inducing effect exerted by statins on autophagy, which could explain their anticancer potential.

c-Myc-Regulated lncRNA-IGFBP4 Suppresses Autophagy in Cervical Cancer-Originated HeLa Cells

“…Autophagy is a biological process through which cells keeps balance in the homeostasis via the lysosomal degradation during cellular development and in the stress conditions [ 33 , 34 ]. It is generally considered a survival mechanism through which cells remove unwanted, misfolded, or aggregated proteins; damaged organelles; and intracellular pathogens [ 35 , 36 ], and autophagic cell death is considered a nonapoptotic cell death [ 37 , 38 ].…”

Don’t Judge a Book by Its Cover: The Role of Statins in Liver Cancer

“…The induced activation of autophagy by statins might exert a significant and robust influence, diminishing their anti-cancer efficacy. This process is under the regulation of two signaling pathways: the mammalian target of rapamycin (mTOR) and AMPK [78].…”

“…Considering the dual role of autophagy in hepatocellular carcinoma (HCC), the importance of sustaining balanced autophagy activity within the PI3K/AKT/mTOR pathway to enable statins to stimulate autophagy in HCC. This action triggers an autophagic response mechanism due to the use of statins on the PI3K/AKT/mTOR signaling pathway [78].…”

The effects of statin therapy on brain tumors, particularly glioma: a review

“…The use of statins was associated with a slightly lower overall cancer incidence compared with nonusers and those who took other lipid-lowering medications [ 64 , 65 ]. In-vitro and in-vivo studies revealed that statins might be effective in cancer prevention and/or treatment via inhibiting tumor growth and inducing apoptosis [ 66 , 67 ]. Further, statins showed cytotoxic and antiproliferative effects against in several human cancer cell lines [ 66 , 68 , 69 ].…”

“…In-vitro and in-vivo studies revealed that statins might be effective in cancer prevention and/or treatment via inhibiting tumor growth and inducing apoptosis [ 66 , 67 ]. Further, statins showed cytotoxic and antiproliferative effects against in several human cancer cell lines [ 66 , 68 , 69 ]. Furthermore, statins treatment upregulated the expression of the proapoptotic proteins and downregulated the expression of antiapoptotic proteins in tumor cells [ 70 ].…”