Induction of p53-Independent Apoptosis and G1 Cell Cycle Arrest by Fucoidan in HCT116 Human Colorectal Carcinoma Cells
AbstractIt is well known that fucoidan, a natural sulfated polysaccharide present in various brown algae, mediates anticancer effects through the induction of cell cycle arrest and apoptosis. Nevertheless, the role of tumor suppressor p53 in the mechanism action of fucoidan remains unclear. Here, we investigated the anticancer effect of fucoidan on two p53 isogenic HCT116 (p53+/+ and p53−/−) cell lines. Our results showed that inhibition of cell viability, induction of apoptosis and DNA damage by treatment with fucoidan were similar in two cell lines. Flow cytometric analysis revealed that fucoidan resulted in G1 arrest in the cell cycle progression, which correlated with the inhibition of phosphorylation of retinoblastoma protein (pRB) and concomitant association of pRB with the transcription factor E2Fs. Furthermore, treatment with fucoidan obviously upregulated the expression of cyclin-dependent kinase (CDK) inhibitors, such as p21WAF1/CIP1 and p27KIP1, which was paralleled by an enhanced binding with CDK2 and CDK4. These events also commonly occurred in both cell lines, suggesting that fucoidan triggered G1 arrest and apoptosis in HCT116 cells by a p53-independent mechanism. Thus, given that most tumors exhibit functional p53 inactivation, fucoidan could be a possible therapeutic option for cancer treatment regardless of the p53 status. View Full-Text
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Park, H.Y.; Park, S.-H.; Jeong, J.-W.; Yoon, D.; Han, M.H.; Lee, D.-S.; Choi, G.; Yim, M.-J.; Lee, J.M.; Kim, D.-H.; Kim, G.-Y.; Choi, I.-W.; Kim, S.; Kim, H.-S.; Cha, H.-J.; Choi, Y.H. Induction of p53-Independent Apoptosis and G1 Cell Cycle Arrest by Fucoidan in HCT116 Human Colorectal Carcinoma Cells. Mar. Drugs 2017, 15, 154.
Park HY, Park S-H, Jeong J-W, Yoon D, Han MH, Lee D-S, Choi G, Yim M-J, Lee JM, Kim D-H, Kim G-Y, Choi I-W, Kim S, Kim H-S, Cha H-J, Choi YH. Induction of p53-Independent Apoptosis and G1 Cell Cycle Arrest by Fucoidan in HCT116 Human Colorectal Carcinoma Cells. Marine Drugs. 2017; 15(6):154.Chicago/Turabian Style
Park, Hye Y.; Park, Shin-Hyung; Jeong, Jin-Woo; Yoon, Dahye; Han, Min H.; Lee, Dae-Sung; Choi, Grace; Yim, Mi-Jin; Lee, Jeong M.; Kim, Do-Hyung; Kim, Gi-Young; Choi, Il-Whan; Kim, Suhkmann; Kim, Heui-Soo; Cha, Hee-Jae; Choi, Yung H. 2017. "Induction of p53-Independent Apoptosis and G1 Cell Cycle Arrest by Fucoidan in HCT116 Human Colorectal Carcinoma Cells." Mar. Drugs 15, no. 6: 154.
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