Anticancer Activity and Molecular Mechanism of Momordica cochinchinensis Seed Extract in Chronic Myeloid Leukemia Cells

Abstract

Targeting Bcr-Abl is the key to the treatment of chronic myeloid leukemia. Despite great progress in the treatment of patients with chronic CML, advanced CML patients are still unable to obtain effective and safe drugs. Momordica cochinchinensis seed is the dried ripe seed of Momordica cochinchinensis, which is a kind of fruit and consumed for dietary as well as medicinal uses. This study aimed to investigate the anticancer activity of Momordica cochinchinensis seed extract (MCSE) in CML cells. CML cells (KBM5 and KBM5-T315I) were treated with MCSE and analyzed for growth, apoptosis, and signal transduction. Nude mouse xenograft model was used to evaluate the antitumor activity of MCSE In Vivo. MCSE significantly reduced the cell viability of CML cells, triggered G0/G1 phase arrest in KBM5 cells and S phase arrest in KBM5-T315I cells. Concurrently, MCSE caused the activation of caspase-3, -8, -9, PARP and the degradation of Mcl-1, ultimately triggering endogenous and exogenous cell apoptosis. Meanwhile, MCSE downregulated Bcr-Abl levels and its downstream signaling pathways. Additionally, MCSE inhibited the growth of CML cells in nude mouse xenografts. Taken together, this study demonstrated the anticancer mechanism of MCSE, namely blocking Bcr-Abl and downregulating Mcl-1, and finally induced apoptosis of CML cells.

Acknowledgments

The authors are grateful to the Laboratory of Basic Medicine, Medical School, Kunming University of Science and Technology, where some experiments were performed.

Disclosure statement

The authors report no conflict of interest.

Authors’ contributions

ZA, CM and LC conceived and designed the study. Experiments were performed by ZA, CM, RW, XC, JY and GL. The manuscript was wrote by ZA and LC. YL and LC reviewed and edited the manuscript and participated in the design of the study.

Additional information

Funding

This study was financed by Yunnan Provincial Department of Education Science Research Fund (grant No. 2021J0061), the National Natural Science Fund of China (grant No. 81760109 and grant No. 81460032) and Natural Science Fund of Kunming University of Science and Technology (grant No. KKSY201460068).