Apigenin induces autophagic cell death in human papillary thyroid carcinoma BCPAP cells

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.

Role of Apigenin in Cancer Prevention via the Induction of Apoptosis and Autophagy

“…The cells treated with 50 μmol/L apigenin showed a high rate of autophagic vacuole formation, and the cells treated with 100 μmol/L showed a high rate of cells in apoptosis 89. A recent study reported that apigenin could induce autophagic cell death in human thyroid cancer BCPAP cells, as evidenced by Beclin-1 accumulation, conversion of LC3 protein, p62 degradation, and significantly increased AVO formation 90. These results suggest that apigenin simultaneously induced apoptosis and autophagy.…”

“…The role of autophagy in cancer cells is dichotomous, with some reports demonstrating autophagy helps cells to survive under stress, and other reports indicating that autophagy ends in apoptosis in the absence of cell recovery. Zhang et al90 found that apigenin could induce both apoptosis and autophagy, while inhibition of autophagy with the small molecule inhibitor 3-MA reduced cell death, indicating that apigenin was associated with autophagic cell death in BCPAP cells. Ruela-de-Sousa and et al86 investigated the molecular mode of action of apigenin and found that apigenin-induced autophagy was not followed by apoptosis in TF1 leukemia cells.…”

Apigenin inhibits renal cell carcinoma cell proliferation

“…[22] reported that apigenin directly bound DNA in prostate epithelial cell lines, although the mechanisms by which this binding may induce DNA damage must be further explored. Apigenin-induced G2/M phase accumulation and apoptosis have been frequently reported [4, 5, 23–25]. However, delayed cell cycle progression at G1/S phase is also observed in several kinds of malignant tumors [26–28].…”

Plant Flavone Apigenin: an Emerging Anticancer Agent

“…Thus, along with Akt inhibitors, apigenin can further enhance the efficacy of radioiodine therapy for thyroid cancer patients [195]. Apigenin-induced cell death has been shown to involve autophagy in papillary thyroid cancer, perhaps because of ROS stimulation, induction of DNA damage and G2/M phase cell cycle arrest [196]. Targeted radioiodine therapy, used in thyroid cancer, depends on thyrotropin-mediated selective stimulation of Na+/I− Symporter (NIS)-mediated radioactive iodide uptake (RAIU) by thyroid cells.…”