Amide Derivative of Arjunolic Acid TA-1,4-BiP Enhances ROSmediated Apoptosis in Colorectal Cancer Cells.

Introduction: Arjunolic acid, a well-known natural product with various medicinal properties, was isolated from the heartwood of Terminalia arjuna. Various amides of arjunolic acid were synthesized using different aryl and cyclic amines, characterized, and evaluated for their anti-cancer activities at the National Cancer Institute (NCI).

Method: All the derivatives were active against all the cell lines of NCI compared to the parent molecule arjunolic acid. Eight compounds were selected for dose-dependent activity based on the preliminary results. IC50 of selected eight compounds was evaluated. Based on IC50 values against various cell lines, compound 2l was further investigated to understand the mechanism of action against HCT-116 and CT-26 colon cancer cell lines.

Result: Mechanistic studies of compound 2l in these two cell lines demonstrated that compound 2l arrested the colon cancer cells at the G/G1 phase. Compound 2l-treated cells were also found to have an increased percentage of ROS compared to untreated cells. It induced apoptosis in both these cell lines.

Conclusion: Compound 2l was found to inhibit cancer growth in the mice model and was very effective against all the cancer cell lines. Therefore, it could be used for further development to treat colon cancer.