Terminalia bellirica (TB) has been used in traditional Indian medical system, Ayurveda. However, the mechanism underlying the efficacy of the TB extract against oral squamous cell carcinoma (OSCC) is yet to be explored. The present study established a connecting link between the TB extract induced apoptosis and autophagy in relation to reactive oxygen species (ROS). Our study revealed, that gallic acid in the TB extract possess a strong free radical scavenging capacity contributing towards the selective anti-proliferative activity. Furthermore, TB extract markedly enhanced the accumulation of ROS that facilitated mitochondrial apoptosis through DNA damage, indicating ROS as the vital component in regulation of apoptosis. This effect was effectively reversed by the use of a ROS scavenger, N-acetyl cysteine (NAC). Moreover, it was observed to induce autophagy; however, it attenuated the autophagosome-lysosome fusion in Cal33 cells without altering the lysosomal activity. Pharmacological inhibitors of autophagy, namely, 3-methyladenine and chloroquine, were demonstarated to regulate the stage-specific progression of autophagy post treatment with the TB extract, favouring subsequent activation of apoptosis. These findings revealed, presence of gallic acid in TB extract below NOAEL value causes oxidative upset in oral cancer cells and promote programmed cell death which has a potential therapeutic value against oral squamous cell carcinoma.

中文翻译：

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榄仁提取物通过调节口腔鳞状细胞癌中的细胞凋亡和自噬来诱导抗癌活性。

榄仁（Terminalia bellirica，TB）已用于印度传统医疗系统阿育吠陀（Ayurveda）。然而，TB提取物抗口腔鳞状细胞癌（OSCC）功效的潜在机制尚待探索。本研究建立了TB提取物诱导的细胞凋亡与自噬相关的活性氧（ROS）之间的联系。我们的研究表明，TB提取物中的没食子酸具有很强的清除自由基的能力，有助于选择性的抗增殖活性。此外，TB提取物显着增强了ROS的积累，从而通过DNA损伤促进了线粒体的凋亡，表明ROS是调节细胞凋亡的重要成分。通过使用ROS清除剂N-乙酰半胱氨酸（NAC），可以有效地逆转这种效果。而且，观察到诱导自噬；但是，它减弱了Cal33细胞中自噬体与溶酶体的融合，而没有改变溶酶体的活性。自噬的药理抑制剂，即3-甲基腺嘌呤和氯喹，被证明可以调节TB提取物治疗后自噬的阶段特异性进程，有利于随后的凋亡激活。这些发现表明，在低于NOAEL值的TB提取物中存在没食子酸会导致口腔癌细胞的氧化不安定，并促进程序性细胞死亡，这对口腔鳞状细胞癌具有潜在的治疗价值。证明了用TB提取物调节自噬后阶段自噬的特定阶段进程，有利于随后的细胞凋亡激活。这些发现表明，在低于NOAEL值的TB提取物中存在没食子酸会导致口腔癌细胞的氧化不安定，并促进程序性细胞死亡，这对口腔鳞状细胞癌具有潜在的治疗价值。证明了用TB提取物调节自噬后阶段自噬的特定阶段进程，有利于随后的细胞凋亡激活。这些发现表明，在低于NOAEL值的TB提取物中存在没食子酸会导致口腔癌细胞的氧化不安定，并促进程序性细胞死亡，这对口腔鳞状细胞癌具有潜在的治疗价值。