Theaflavin-3, 3'-digallate induces apoptosis and G2 cell cycle arrest through the Akt/MDM2/p53 pathway in cisplatin-resistant ovarian cancer A2780/CP70 cells

  • Authors:
    • Youying Tu
    • Eunhye Kim
    • Ying Gao
    • Gary O. Rankin
    • Bo Li
    • Yi Charlie Chen
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  • Published online on: April 6, 2016     https://doi.org/10.3892/ijo.2016.3472
  • Pages: 2657-2665
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Abstract

Ovarian cancer is the most lethal gynecological cancer among women worldwide. Adverse side effects and acquired resistance to conventional platinum based chemotherapy are major impediments in ovarian cancer treatment, and drive the development of more selective anticancer drugs that target cancer-specific defects. In this study, theaflavin-3, 3'-digallate (TF3), the major theaflavin monomer in black tea, exhibited a potent growth inhibitory effect on the cisplatin-resistant ovarian cancer A2780/CP70 cells (IC50, 23.81 µM), and was less cytotoxic to a normal ovarian IOSE‑364 cells (IC50, 59.58 µM) than to the cancer cells. Flow cytometry analysis indicated that TF3 induced preferential apoptosis and G2 cell cycle arrest in A2780/CP70 cells with respect to IOSE‑364 cells. TF3 induced apoptosis through both the intrinsic and extrinsic apoptotic pathways, and caused G2 cell cycle arrest via cyclin B1 in A2780/CP70 cells. The p53 protein played an important role in TF3-induced apoptosis and G2 cell cycle arrest. TF3 might upregulate the p53 expression via the Akt/MDM2 pathway. Our findings help elucidate the mechanisms by which TF3 may contribute to the prevention and treatment of platinum-resistant ovarian cancer.
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June-2016
Volume 48 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Tu Y, Kim E, Gao Y, Rankin GO, Li B and Chen YC: Theaflavin-3, 3'-digallate induces apoptosis and G2 cell cycle arrest through the Akt/MDM2/p53 pathway in cisplatin-resistant ovarian cancer A2780/CP70 cells. Int J Oncol 48: 2657-2665, 2016.
APA
Tu, Y., Kim, E., Gao, Y., Rankin, G.O., Li, B., & Chen, Y.C. (2016). Theaflavin-3, 3'-digallate induces apoptosis and G2 cell cycle arrest through the Akt/MDM2/p53 pathway in cisplatin-resistant ovarian cancer A2780/CP70 cells. International Journal of Oncology, 48, 2657-2665. https://doi.org/10.3892/ijo.2016.3472
MLA
Tu, Y., Kim, E., Gao, Y., Rankin, G. O., Li, B., Chen, Y. C."Theaflavin-3, 3'-digallate induces apoptosis and G2 cell cycle arrest through the Akt/MDM2/p53 pathway in cisplatin-resistant ovarian cancer A2780/CP70 cells". International Journal of Oncology 48.6 (2016): 2657-2665.
Chicago
Tu, Y., Kim, E., Gao, Y., Rankin, G. O., Li, B., Chen, Y. C."Theaflavin-3, 3'-digallate induces apoptosis and G2 cell cycle arrest through the Akt/MDM2/p53 pathway in cisplatin-resistant ovarian cancer A2780/CP70 cells". International Journal of Oncology 48, no. 6 (2016): 2657-2665. https://doi.org/10.3892/ijo.2016.3472