Inhibiting reactive oxygen species-dependent autophagy enhanced baicalein-induced apoptosis in oral squamous cell carcin
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ORIGINAL PAPER
Inhibiting reactive oxygen species-dependent autophagy enhanced baicalein-induced apoptosis in oral squamous cell carcinoma Bo Li1 • Mei Lu1 • Xin-Xiang Jiang1 • Meng-Xiong Pan1 • Jun-Wu Mao1 Mei Chen1
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Received: 23 November 2016 / Accepted: 24 January 2017 Ó The Japanese Society of Pharmacognosy and Springer Japan 2017
Abstract Autophagy modulation has been considered a potential therapeutic strategy for oral squamous cell carcinoma (OSCC). A previous study confirmed that baicalein might possess significant anti-carcinogenic activity. However, whether baicalein induces autophagy and its role in cell death in OSCC are still unclear. The aim of this study was to investigate the anticancer activity and molecular targets of baicalein in OSCC in vitro. In this study, we found that baicalein induced significant apoptosis in OSCC cells Cal27. In addition to showing apoptosis induction, we also demonstrated baicalein-induced autophagic response in Cal27 cells. Moreover, pharmacologically or genetically blocking autophagy enhanced baicalein-induced apoptosis, indicating the cytoprotective role of autophagy in baicalein-treated Cal27 cells. Importantly, we found that baicalein triggered reactive oxygen species (ROS) generation in Cal27 cells. Furthermore, N-acetyl-cysteine, a ROS scavenger, abrogated the effects of baicalein on ROS-dependent autophagy. Therefore, we found that baicalein increased autophagy through the promotion of ROS signaling pathways in OSCC. These data also suggest that a strategy of blocking ROS-dependent autophagy to enhance the activity of baicalein warrants further attention for the treatment of OSCC. Keywords Baicalein Autophagy Reactive oxygen species Apoptosis OSCC
& Mei Chen [email protected] 1
Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Guilin Medical University, Guilin, Guangxi Zhuang Autonomous Region, People’s Republic of China
Introduction Oral squamous cell carcinoma (OSCC) is a malignancy found worldwide with an aggressive process and dismal prognosis. OSCC is also highly correlated with tobacco and alcohol abuse, betel quid chewing and human papilloma virus infection [1]. Mortality remains high because of the emergence of therapy-resistant local recurrences and the development of distant metastases [2, 3]. Thus, the development of potential alternative therapies and the discovery of novel mechanisms underlying OSCC initiation and progression are necessary and urgent. A large number of studies have focused on chemopreventive activities of phytochemicals [4–6]. Baicalein (Fig. 1a), isolated from the Chinese medicinal herb Scutellaria baicalensis Georgi (Huangqin in Chinese), is a flavonoid with various pharmacological effects [7, 8]. It has recently attracted considerable attention because of accumulating data demonstrating its strong inhibitory effect on non-small cell lung cancer [9], human prostate cancer [10], human breast cancer [11], and others [12, 13]. Several studies have revealed that baicalein causes cell cycle arrest and tri
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