Garcinone Inhibits Nasopharyngeal Carcinoma Cell Growth And Arrests Cell Cycle Via Modulating The Expression Of Atr/Stat3/4e-Bp1

Nasopharyngeal carcinoma (NPC) is one of the common head and neck malignancies. Radiotherapy and chemotherapy are the standard treatments for NPC. Garcinone, a natural compound isolated from Garcinia oblongifolia Champ., is a xanthone derivative and has been shown to have potential cytotoxic effects on certain cancer types. However, there have been limited studies performed on its effects on NPC cells and the mechanisms of these effects remain unknown. In this study, we firstly found that garcinone significantly inhibited cell viability of human NPC cell lines CNE1, CNE2, HK1, and HONE1. This inhibition was in a time- and dose-dependent manner. Then, flow cytometry analysis was performed on cell cycle analysis. We observed that garcinone arrested cell cycle at S phase. With 10μM of high-dose garcinone treatment, the cells exhibited necrotic morphology changes including cell swelling, rough endoplasmic reticulum (ER) degranulation, ER dilatation, mitochondria swelling, and vacuolar degeneration. Finally, we found that garcinone stimulated the expression levels of ATR and 4E-BP1, while efficiently inhibited the expression levels of Cyclin B1, Cyclin D1, Cyclin E2, cdc2, CDK7, and Stat3. Collectively, the ability of garcinone to inhibit NPC in vitro suggested that garcinone might be a novel agent for the management of NPC. Supported by NSFC Key Project 81130046; NSFC Project 81171993 and NSFC81272415; Guangxi Key Projects 2013GXNSFEA053004 and 2012GXNSFCB053004; Guangxi Ministry of Education 201202ZD022 and 201201ZD004. Citation Format: Yudui Xia, Xia Liu, Chunllin Zou, Hongwei Guo, Yeguo Yang, Yong Lei, Jian Zhang, Yi Lu. Garcinone inhibits nasopharyngeal carcinoma cell growth and arrests cell cycle via modulating the expression of ATR/Stat3/4E-BP1. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2187.