Qi Shuo, Li Dandan, Deng Fangping, Fu Shuxin, Chen Shuangshuang, Zou Hong, Wen Lixiang, Tang Qun
Hunan University of Chinese Medicine, Yuelu District, Changsha City, 410208, Hunan Province, China.
Hunan University of Chinese Medicine, Yuelu District, Changsha City, 410208, Hunan Province, China.
Eur J Pharmacol. 2025 Sep 15;1003:177935. doi: 10.1016/j.ejphar.2025.177935. Epub 2025 Jul 16.
Oral squamous cell carcinoma is one of the most common malignant tumors in the oral and maxillofacial region, with insidious morbidity, high mortality rate, and limited therapeutic methods at present, so there is an urgent need for the development of new therapeutic drugs in the clinic.
This study aims to investigate the therapeutic potential of brusatol (BRT)-a natural compound isolated from Brucea javanica (L.) Merr.-for treating oral squamous cell carcinoma, with a focus on evaluating its antitumor efficacy and deciphering the underlying molecular mechanisms.
We conducted in vitro and in vivo experiments respectively. Firstly, we found that brusatol (BRT) can effectively inhibit the growth rate of the nude mouse heterotopic transplantation tumor model constructed with Cal-27 cells. Secondly, it was proved that brusatol (BRT) can promote the ferroptosis of Cal-27 cells, reduce their survival rate, and inhibit their growth and migration capabilities. Further research revealed that Nrf2, as a key factor in facilitating ferroptosis by brusatol (BRT), can suppress the expression of its downstream target genes GCLC and SLC7A11, leading to depletion of intracellular GSH, accumulation of Fe and ROS, and the occurrence of ferroptosis in Cal-27 cells.
In summary, our study confirms that brusatol (BRT) can promote ferroptosis and improve oral squamous cell carcinoma by inhibiting the Nrf2/GCLC pathway.
This discovery makes brusatol (BRT) a promising therapeutic agent for the treatment of oral squamous cell carcinoma.
口腔鳞状细胞癌是口腔颌面部最常见的恶性肿瘤之一，发病率隐匿，死亡率高，目前治疗方法有限，因此临床上迫切需要开发新的治疗药物。
本研究旨在探讨从鸦胆子中分离出的天然化合物毛果巴豆醇（BRT）治疗口腔鳞状细胞癌的潜力，重点评估其抗肿瘤疗效并阐明潜在的分子机制。
我们分别进行了体外和体内实验。首先，我们发现毛果巴豆醇（BRT）能有效抑制用Cal-27细胞构建的裸鼠异位移植瘤模型的生长速度。其次，证明了毛果巴豆醇（BRT）可促进Cal-27细胞的铁死亡，降低其存活率，并抑制其生长和迁移能力。进一步研究表明，Nrf2作为毛果巴豆醇（BRT）促进铁死亡的关键因子，可抑制其下游靶基因GCLC和SLC7A11的表达，导致细胞内谷胱甘肽耗竭、铁和活性氧积累，从而使Cal-27细胞发生铁死亡。
总之，我们的研究证实毛果巴豆醇（BRT）可通过抑制Nrf2/GCLC途径促进铁死亡并改善口腔鳞状细胞癌。
这一发现使毛果巴豆醇（BRT）成为治疗口腔鳞状细胞癌的一种有前景的治疗药物。
