Cholesterol: A Potential Target for Intervention in Anti-Cancer Therapy

Being polycyclic hydrocarbon, cholesterol has the quality for making DNA adduct within cell nucleus. Structurally cholesterol and its epoxide are very close to polycyclic carcinogenic precursor e.g. benzo-alpha-pyrene, which is well known for its carcinogenic pulse by forming adduct to chromosomal DNA. In fact normal cross membrane transports of cholesterol, either on cell surface or on nuclear membrane turn desynchronized in cancer tumor cells. A cholesterol loaded cell nucleus has been correlated to wobbly cell cycle operation and aberrant cell proliferation in many cancer type viz. leukemia, breast carcinoma, prostate carcinoma etc. A reprogrammed cholesterol metabolism affects tumor associated immune cell activity, cellular apoptosis and kinetics of cell survival. In fact, cholesterol concentration within cell nucleus has been found correlated with cellular life span. In tumor microenvironment intracellular cholesterol concentration varies from one to another cell type. While it increases within tumor cells, the surrounding immune cells die because of scarcity of intracellular cholesterol concentration. Intervention of this biphasic role of cholesterol in and around the cancer tumor could be a model target for anti-cancer therapeutic management.

Keywords: Anti-cancer therapy, Breast cancer, Carcinogenesis, Cholesterol homeostasis, Leukemia, Low density lipoprotein, Low density lipoprotein receptor, Metformin, Nuclear cholesterol, Peripheral type benzodiazepine receptor, PD-1, PD-L1, Polycyclic hydrocarbon, Prostate cancer, Statin.