Punicalagin Restricts Growth, Promotes Apoptosis, and Reduces Invasion in Human Gastric Cancer Cells

Author:

Sun Ding-Ping12,Uen Yih-Huei3456,Kang Nai-Wen7,Chang Chun-Chao8910,Tian Yu-Feng1,Fang Chia-Lang1112,Lin Kai-Yuan13ORCID

Affiliation:

1. Department of Surgery, Chi Mei Medical Center, Tainan, Taiwan

2. Department of Food Science and Technology, Chia Nan University of Pharmacy and Science, Tainan, Taiwan

3. Department of Surgery, Asia University Hospital, Taichung, Taiwan

4. Department of Biotechnology, Asia University, Taichung, Taiwan

5. Department of Surgery, Tainan Municipal An-Nan Hospital, Tainan, Taiwan

6. Department of Surgery, Kuo General Hospital, Tainan, Taiwan

7. Division of Hematology and Oncology, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan

8. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan

9. Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, Taipei Medical University, Taipei, Taiwan

10. TMU Research Center for Digestive Medicine, Taipei Medical University, Taipei, Taiwan

11. Department of Pathology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

12. Department of Pathology, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan

13. Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan

Abstract

This research investigated the anticancer properties of punicalagin, a prominent bioactive polyphenol extracted from Punica granatum L, in human gastric cancer cell lines. Normal and gastric cancer cells were exposed to different doses of punicalagin for various durations. Punicalagin exhibited cytotoxic effects on gastric cancer cells in a dose- and time-dependent fashion, while sparing normal gastric epithelial cells. It is noteworthy that among the 3 gastric cancer cells, HGC-27 cells were more resistant to punicalagin than 23,132/87 and AGS cells. Furthermore, punicalagin triggered apoptosis in gastric cancer cells, evidenced by a rise in both early and late apoptotic cell percentages. Western blot analysis further revealed that punicalagin elevated the levels of activated caspase-3. Conversely, punicalagin curtailed cell invasion and reduced the expression of MMP-2, MMP-9, Snail, and Slug. From a mechanistic standpoint, Western blotting indicated that punicalagin might inhibit the Erk and NF-κB pathways, leading to apoptosis induction and the inhibition of cell invasion in gastric cancer cells. These results indicate that punicalagin promotes apoptosis and inhibits cell invasion in gastric cancer cells by activating caspase-3 and suppressing MMP-2, MMP-9, Snail, and Slug through the inhibition of the Erk and NF-κB pathways.

Funder

Chi Mei Medical Center

Publisher

SAGE Publications

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