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Introduction
Malignancies remain a major challenge to global public health (1). One of the most common head and neck malignancies worldwide, especially in southern China, Southeast Asia, and North Africa, is nasopharyngeal carcinoma (NPC) (2). There are three subtypes of NPC, classified by the World Health Organization, that include squamous cell carcinoma, non-keratinizing carcinoma and undifferentiated carcinoma (3).
Radiotherapy is the standard treatment for early-stage NPC, but chemotherapy is also very important in the standard treatment of locally advanced and metastatic NPC. The common chemotherapies used to treat NPC are cisplatin, carboplatin, 5-fluorouracil, gemcitabine, paclitaxel, anthracyclines, bleomycin, epirubicin and cetuximab (2). However, one of the major obstacles in successfully treating advanced NPC is the development of drug resistance, which can result from a variety of factors, including increased DNA damage tolerance (4). Because of this major obstacle that drug resistance poses, new and better treatment options for NPC are urgently needed.
In the last few decades, natural compounds have gained increasing attention as a source of potential anticancer agents. Xanthones are oxygen-containing heterocyclic compounds widely distributed in various plants and microorganisms. It is well known that xanthones have remarkable pharmacological effects, such as anticancer, antioxidant, anti-inflammatory, antidiabetic, antimicrobial, antithrombotic and hepatoprotective activities (5–7). Among them, the anticancer potential of xanthones has drawn an increasing amount of attention. For example, some xanthones, such as gambogic acid (8–12) and α-mangostin (13–16), have been shown to exhibit anticancer properties, including antiproliferation, antiangiogenesis and antimetastasis.
Garcinone C (C23H26O7, MW 414.5, Fig. 1), a xanthone derivative, is a natural compound extracted from Garcinia oblongifolia Champ. (a traditional Chinese medicine) that is used as an anti-inflammatory, analgesia, astringency and granulation-promoting medicine. Recently, it was reported that garcinone C exhibits cytotoxicity against MCF-7, A549, Hep-G2 and CNE human cancer cell lines in vitro (17). However, the function and molecular mechanism of this compound in cell growth and cell cycle progression have not been yet elucidated. In the present study, CNE1 (well-differentiated squamous cell carcinoma), CNE2 (non-keratinizing carcinoma), HK1 (well-differentiated squamous cell carcinoma) and HONE1 (undifferentiated carcinoma) NPC cells were treated with different concentrations of garcinone C and then subjected to biochemical, microscopic, flow cytometric, and molecular analyses to determine the efficacy and mechanism of action...