Delving KS-01 as a Novel Therapeutic Strategy in Treating Breast Cancer

Abstract

Background: Cancer cells have an increased need for cholesterol, which is required for cell membrane integrity. Cholesterol accumulation has been described in various malignancies including breast cancer. Cholesterol has also been known to be the precursor of estrogen and vitamin D, both of which play a key role in the histology of breast cancer. Thus, depleting the cholesterol levels in cancer cells is a proposed innovative strategy to treat cancer. Therefore, novel cholesterol-depleting compounds are currently being investigated. KS-01 is a cyclic amylose oligomer composed of glucose units. It solubilizes the cholesterol and is proven to be toxicologically benign in humans. Aim: To deplete cholesterol from cancer cells and investigating KS-01 to be a clinically useful compound. Our work provides preliminary experimental evidences to support this hypothesis. Methods: MTT assay (growth inhibition) APO percentage assay (apoptosis) Western blotting (protein expression) MOMP assay (mitochondrial membrane potential for apoptosis) Caspase 3,7 assay (caspase 3,7 activity for apoptosis) Cholesterol assay (to check cholesterol levels) RT-PCR (gene expression). Results: We identified the potency of KS-01 in vitro against two breast cancer cell lines: MCF-7 (estrogen positive, ER+), MDA-MB-231 (estrogen negative, ER-) and compared the results against two normal cell lines: MRC-5 (normal human lung fibroblasts) and HEK-293 (normal human embryonic kidney cells) using cytotoxic, apoptosis, protein expression and cholesterol based assays. KS-01 treatment reduced intracellular cholesterol resulting in significant breast cancer cell growth inhibition through apoptosis. The results hold true for both ER+ and ER-. Conclusion: The data obtained from our experiments suggest that KS-01 can prevent cholesterol accumulation in breast cancer cells and is a promising new anticancer agent. We are currently testing our hypothesis in vivo to validate the in vitro results. N.B: We have submitted the preliminary data to WITS ENTERPRISE (university's internal patenting agency). Once we get our in vivo data, the compound would be patented for its mechanism of action in breast cancer.