口腔鳞状细胞癌（OSCC）是世界上最常见的恶性肿瘤，死亡率惊人。尽管治疗策略和药物开发取得了进步，但总体生存率仍然很低。因此，开发具有最小脱靶效应的替代或补充抗癌药物势在必行。尿石素 A 是人体肠道微生物组内源性产生的鞣花酸和鞣花单宁的微生物代谢产物，被认为具有抗癌活性。然而，尿石素 A 在 OSCC 中的抗肿瘤作用尚未阐明。在本研究中，我们检测了尿石素A是否抑制OSCC细胞系中的细胞生长并诱导细胞凋亡和自噬依赖性细胞死亡。本研究旨在评估尿石素A抑制OSCC的潜力及其对OSCC增殖和侵袭的调节作用。体外和体内小鼠模型。我们评估了尿石素 A 是否可以在体外和体内小鼠模型中诱导 OSCC 细胞死亡。对尿石素 A 处理的 OSCC 细胞系进行流式细胞术和免疫印迹分析表明，尿石素 A 通过诱导内质网应激并随后抑制 AKT 和 mTOR 信号传导，磷酸化 mTOR 和 4EBP1 水平降低证明了这一点。这进一步揭示了细胞凋亡和自噬信号通路之间可能存在交叉对话。体内研究表明，尿石素 A 治疗可缩小肿瘤大小，并显示 mTOR、ERK1/2 和 Akt 水平下降，以及增殖标记物 Ki67 下降。综上所述，体外和体内数据表明，尿石素 A 是一种潜在的抗癌剂，并且抑制 AKT/mTOR/ERK 信号传导对于尿石素 A 诱导的口腔癌生长抑制至关重要。尿石素 A 发挥其抗肿瘤活性通过诱导 OSCC 中的细胞凋亡和自噬途径。我们的研究结果表明，尿石素 A 通过诱导内质网应激并随后抑制 AKT 和 mTOR 信号传导，显着诱导口腔鳞状细胞癌的细胞死亡，磷酸化 mTOR 和 4EBP1 水平降低就证明了这一点。尿石素 A 在体外和体内小鼠模型中均显着抑制肿瘤生长，这表明其作为预防和治疗 OSCC 的抗癌药物的潜力。今后，我们的研究结果为尿石素 A 在预防和治疗 OSCC 中的治疗潜力提供了新的见解。版权所有 © 2024。由 Elsevier GmbH 出版。

Oral squamous cell carcinoma (OSCC) is the most prevalent malignancy in the world with an alarming rate of mortality. Despite the advancement in treatment strategies and drug developments, the overall survival rate remains poor. Therefore, it is imperative to develop alternative or complimentary anti cancer drugs with minimum off target effects. Urolithin A, a microbial metabolite of ellagic acid and ellagitannins produced endogenously by human gut micro biome is considered to have anti-cancerous activity. However anti tumorigenic effect of urolithin A in OSCC is yet to be elucidated. In this study, we examined whether urolithin A inhibits cell growth and induces both apoptosis and autophagy dependent cell death in OSCC cell lines.The present study aims to evaluate the potential of urolithin A to inhibit OSCC and its regulatory effect on OSCC proliferation and invasion in vitro and in vivo mouse models.We evaluated whether urolithin A could induce cell death in OSCC in vitro and in vivo mouse models.Flow cytometric and immunoblot analysis on Urolithin A treated OSCC cell lines revealed that urolithin A markedly induced cell death of OSCC via the induction of endoplasmic reticulum stress and subsequent inhibition of AKT and mTOR signaling as evidenced by decreased levels of phosphorylated mTOR and 4EBP1. This further revealed a possible cross talk between apoptotic and autophagic signaling pathways. In vivo study demonstrated that urolithin A treatment reduced tumor size and showed a decrease in mTOR, ERK1/2 and Akt levels along with a decrease in proliferation marker, Ki67. Taken together, in vitro as well as our in vivo data indicates that urolithin A is a potential anticancer agent and the inhibition of AKT/mTOR/ERK signalling is crucial in Urolithin A induced growth suppression in oral cancer.Urolithin A exerts its anti tumorigenic activity through the induction of apoptotic and autophagy pathways in OSCC. Our findings suggest that urolithin A markedly induced cell death of oral squamous cell carcinoma via the induction of endoplasmic reticulum stress and subsequent inhibition of AKT and mTOR signaling as evidenced by decreased levels of phosphorylated mTOR and 4EBP1. Urolithin A remarkably suppressed tumor growth in both in vitro and in vivo mouse models signifying its potential as an anticancer agent in the prevention and treatment of OSCC. Henceforth, our findings provide a new insight into the therapeutic potential of urolithin A in the prevention and treatment of OSCC.Copyright © 2024. Published by Elsevier GmbH.