J Cancer 2019; 10(19):4509-4521. doi:10.7150/jca.31045

Research Paper

Combination of quercetin and cisplatin enhances apoptosis in OSCC cells by downregulating xIAP through the NF-κB pathway

Xin Li1#, Shu Guo2#, Xi-Kun Xiong1, Bao-Ying Peng1, Jun-Ming Huang1, Mei-Fen Chen1, Feng-Yan Wang1, Jian-Ning Wang3✉

1. Guangdong Provincial Center for Disease Control and Prevention, 160 Qunxian Road, Dashi, Panyu District, Guangzhou, Guangdong Province, P.R. China, 511430
2. State Environmental Protection Key Laboratory of Environmental Pollution Health Risk Assessment, South China Institute of Environmental Sciences, Ministry of Environmental Protection, Guangzhou, Guangdong Province, P.R. China, 510655
3. Department of Oral and Maxillofacial Surgery, Guanghua School of Stomatology, Hospital of Stomatology, Institute of Stomatological Research, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Stomatology, 56, Ling Yuan Xi Road, Guangzhou, Guangdong Province, P.R. China, 510055
# These authors contributed equally to this work

Abstract

While cisplatin is a first-line chemotherapeutic drug commonly used to treat patients with oral squamous cell carcinoma (OSCC), the cisplatin-resistance poses a major challenge for its clinical application. Recent studies have shown that quercetin, a natural flavonoid found in various plants and foods possesses an anti-cancer effect. The following study examined the combined effect of quercetin and cisplatin on OSCC apoptosis in vitro and in vivo (using a mice tumor model). We found that quercetin promotes cisplatin-induced apoptosis in human OSCC (cell lines Tca-8113 and SCC-15) by down-regulating NF-κB. Pretreatment of cancer cells with quercetin inhibited the phosphorylation Akt and IKKβ, and led to the suppression of NF-κB and anti-apoptotic protein xIAP. In addition, we observed that the pretreatment of cancer cells with quercetin improves extrinsic and intrinsic apoptosis by activating caspase-8 and caspase-9, respectively. Our in vivo data also indicated that the combination of quercetin and cisplatin may inhibit the xenograft growth in mice. To sum up, our results provide a new evidence for the application of quercetin and cisplatin in OSCC therapy.

Keywords: quercetin, cisplatin, apoptosis, NF-κB, xIAP

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How to cite this article:
Li X, Guo S, Xiong XK, Peng BY, Huang JM, Chen MF, Wang FY, Wang JN. Combination of quercetin and cisplatin enhances apoptosis in OSCC cells by downregulating xIAP through the NF-κB pathway. J Cancer 2019; 10(19):4509-4521. doi:10.7150/jca.31045. Available from http://www.jcancer.org/v10p4509.htm