Apigenin-induced apoptosis is enhanced by inhibition of autophagy formation in HCT116 human colon cancer cells

Lee,Yujin; Sung,Bokyung; Kang,Yong Jung; Kim,Dong Hwan; Jang,Jung-Yoon; Hwang,Seong Yeon; Kim,Minjung; Lim,Hyun Sook; Yoon,Jeong-Hyun; Chung,Hae Young; Kim,Nam Deuk

doi:10.3892/ijo.2014.2339

Apigenin-induced apoptosis is enhanced by inhibition of autophagy formation in HCT116 human colon cancer cells

Authors:
- Yujin Lee
- Bokyung Sung
- Yong Jung Kang
- Dong Hwan Kim
- Jung-Yoon Jang
- Seong Yeon Hwang
- Minjung Kim
- Hyun Sook Lim
- Jeong-Hyun Yoon
- Hae Young Chung
- Nam Deuk Kim
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Affiliations: Division of Pharmacy, College of Pharmacy, Molecular Inflammation Research Center for Aging Intervention (MRCA), Pusan National University, Busan 609-735, Republic of Korea
Published online on: March 13, 2014 https://doi.org/10.3892/ijo.2014.2339
Pages: 1599-1606

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Abstract

Apigenin (4',5,7-trihydroxyflavone) is a natural flavonoid, shown to have chemopreventive and/or anticancer properties in a variety of human cancer cells. The involvement of autophagy in apigenin-induced apoptotic cell death of HCT116 human colon cancer cells was investigated. Apigenin induced suppression of cell growth in a concentration-dependent manner in HCT116 cells. Flow cytometric analyses indicated that apigenin resulted in G2/M phase arrest. This flavone also suppressed the expression of both cyclin B1 and its activating partners, Cdc2 and Cdc25c, whereas the expression of cell cycle inhibitors, such as p53 and p53-dependent p21CIP1/WAF1, was increased after apigenin treatment. Apigenin induced poly (ADP-ribose) polymerase (PARP) cleavage and decreased the levels of procaspase-8, -9 and -3. In addition, the apigenin-treated cells exhibited autophagy, as characterized by the appearance of autophagosomes under fluorescence microscopy and the accumulation of acidic vesicular organelles by flow cytometry. Furthermore, the results of the western blot analysis revealed that the levels of LC3-II, the processed form of LC3-I, was increased by apigenin. Treatment with the autophagy inhibitor 3-methyladenine (3-MA) significantly enhanced the apoptosis induced by apigenin, which was accompanied by an increase in the levels of PARP cleavage. These results indicate that apigenin has apoptosis- and autophagy-inducing effects in HCT116 colon cancer cells. Autophagy plays a cytoprotective role in apigenin-induced apoptosis, and the combination of apigenin and an autophagy inhibitor may be a promising strategy for colon cancer control.

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