Apigenin induces autophagic cell death in human papillary thyroid carcinoma BCPAP cells
Li Zhang1, Xian Cheng, Yanyan Gao
1Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu 214063, China. yuhuixin@jsinm.org.
Abstract:
Apigenin, abundantly present in fruits and vegetables, is recognized as a flavonoid with anti-inflammatory, antioxidant and anticancer properties. In this study, we first investigated the anti-neoplastic effects of apigenin on papillary thyroid carcinoma (PTC) cell line BCPAP cells. Our results show that apigenin inhibited the viability of BCPAP cells in a dose-dependent manner. A large body of evidence demonstrates that autophagy contributes to cell death in certain contexts. In the present study, autophagy was induced by apigenin treatment in BCPAP cells, as evidenced by Beclin-1 accumulation, conversion of LC3 protein, p62 degradation as well as the significantly increased formation of acidic vesicular organelles (AVOs) compared to the control group. 3-MA, an autophagy inhibitor, rescued the cells from apigenin-induced cell death. Notably, apigenin enhanced production of reactive oxygen species (ROS), and subsequent induction of significant DNA damage as monitored by the TUNEL assay. In addition, apigenin treatment caused a significant accumulation of cells in the G2/M phase via down-regulation of Cdc25C expression. Our findings reveal that apigenin inhibits papillary thyroid cancer cell viability by the stimulation of reactive oxygen species (ROS) production, induction of DNA damage, leading to G2/M cell cycle arrest followed by autophagic cell death. Thus, our results provide new insights into the molecular mechanisms underlying apigenin-mediated autophagic cell death and suggest apigenin as a potential chemotherapeutic agent which is able to fight against papillary thyroid cancer.
Insights
Apigenin, a natural compound, effectively reduces papillary thyroid cancer cell viability. It triggers cell death through DNA damage, cell cycle arrest, and autophagy, suggesting its potential as a cancer therapeutic.
Area of Science:
- Oncology
- Molecular Biology
- Natural Product Chemistry
Background:
- Apigenin is a flavonoid found in fruits and vegetables.
- It possesses known anti-inflammatory, antioxidant, and anticancer properties.
- Papillary thyroid carcinoma (PTC) is a significant health concern.
Purpose of the Study:
- To investigate the anti-neoplastic effects of apigenin on the BCPAP papillary thyroid cancer cell line.
- To elucidate the molecular mechanisms underlying apigenin's action on these cancer cells.
Main Methods:
- Cell viability assays were performed on BCPAP cells treated with apigenin.
- Autophagy was assessed by monitoring Beclin-1, LC3 protein conversion, p62 degradation, and acidic vesicular organelles (AVOs).
- Reactive oxygen species (ROS) production, DNA damage (TUNEL assay), and cell cycle progression (Cdc25C expression) were analyzed.
Main Results:
- Apigenin inhibited BCPAP cell viability in a dose-dependent manner.
- Apigenin induced autophagy, evidenced by molecular markers and increased AVOs.
- Autophagy inhibition by 3-MA rescued cells from apigenin-induced death.
- Apigenin increased ROS production, caused DNA damage, and induced G2/M cell cycle arrest via Cdc25C down-regulation.
Conclusions:
- Apigenin exhibits anti-neoplastic effects against papillary thyroid cancer cells.
- Apigenin-induced cell death involves ROS production, DNA damage, G2/M cell cycle arrest, and subsequent autophagic cell death.
- Apigenin shows promise as a potential chemotherapeutic agent for papillary thyroid cancer.
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