Evaluation of D-Mannoheptulose and Doxorubicin as Potential Therapeutic Agents for Breast Cancer by Targeting Glycolysis and Inducing Apoptosis.

Abstract

Cell culture techniques are the vital basis for the majority of experimental cancer research. Targeting cancer cells metabolism is one of the key strategies for controlling the growth of cancer cells. D-Mannoheptulose (MH) (as Phytotherapy) a specific inhibitor, belonging to hexokinase category, to inhibit glycolysis pathway and Doxorubicin (DXR) (as Chemotherapy) has cytotoxic activity against cancer cells and anti-cancer effects by inducing apoptosis. Evaluating the effect of D-Mannoheptulose and Doxorubicin on the normal and breast cancer cell line by determining their anti-tumor activities. Cell culture of normal human mammary epithelial cells (HMECs) and MCF-7 cell line were achieved by using Minimum Essential Medium (MEM) and RPMI-1640 Medium. D-Mannoheptulose, and Doxorubicin stock and diluted solutions were prepared by using phosphate buffer saline (PBS), and dimethyl sulphoxide (DMSO) respectively. HMECs and MCF7 cell line were treated with MH, and DXR, cytotoxicity ratio was determined by methyl thiazolyl tetrazolium (MTT). The findings of study indicated a substantial increase in the cytotoxicity and antiproliferative effects of MH and DXR depending on the concentration gradient against breast cancer cell lines and IC50 values, while on the other hand, there was no significant cytotoxic effect on normal cells. Results of the study revealed that MH, DXR, can result in inhibiting the growth of breast cancer cell lines. This behaviour was mainly due to the increase in cytotoxicity through inhibiting the glycolysis pathway thereby resulting in apoptosis. This further lead to the decrease in HK activity and hence pyruvate as well as ATP amount. Overall, DXR and MH treatment display effective cytotoxic effects against the studied breast cancer cell lines.