Cardiac glycosides from the seeds of Thevetia peruviana and their pro-apoptotic activity toward cancer cells

Abstract

Phytochemical investigation of the seeds of Thevetia peruviana resulted in the isolation of seven cardiac glycosides (1–7), including two new compounds (1 and 2). Cytotoxicity of them toward cancer cell lines P15 (human lung cancer cell), MGC-803 (human gastric cancer cells), SW1990 (human pancreatic cancer cells), and normal hepatocyte cell LO2 suggested that compound 1 could selectively inhibit the proliferation of cancer cell lines with IC₅₀ from 0.05 to 0.15 μM. Pro-apoptotic activity revealed that it induced the apoptosis of MGC-803 cancer cells in a dose-dependent manner. Meanwhile, treatment of MGC-803 cancer cells with 1 resulted in diminution of pro-caspases 3 and 9 and activation of caspases 3 and 9, while it increased the Bax/Bcl-2 ratio in a dose-dependent manner. These meant that 1 induced the apoptosis of cancer cells by involving the intrinsic apoptotic pathway. In addition, the cell cycle distribution of MGC-803 cancer cells treated by 1 revealed that it could lead to cell cycle arrest at the G2/M phase. Altogether, this study suggested that compound 1 may exhibit anticancer activity by its capability of induction of intrinsic apoptosis and cell cycle arrest at G2/M phase.

Keywords:

• Apocynanceae
• Thevetia peruviana
• cardiac glycosides
• cytotoxicity
• pro-apoptotic activity
• cell cycle arrest

Acknowledgments

The authors are grateful to Mr J. F. Tian, Mr C. Z. Lai, Mr Z. F. Qin, and Ms X. Y. Shen for the NMR and HRESIMS measurements. Associate professor Ying Zhang’s help in plant authentication is also appreciated.