Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Afyonkarahisar Health Sciences University, 03200 Afyonkarahisar, Turkey.
Department of Pedodontics, Faculty of Dentistry, Afyonkarahisar Health Sciences University, 03200 Afyonkarahisar, Turkey.
Medicina (Kaunas). 2024 Jul 23;60(8):1192. doi: 10.3390/medicina60081192.
: PIN1 is overexpressed in several human cancers, including prostate cancer, breast cancer, and oral squamous carcinomas. Juglone (J), derived from walnut, was reported to selectively inhibit PIN1 by modifying its sulfhydryl groups. In this study, the potential effects of juglone, also known as PIN1 inhibitor, on oral cancer and carcinogenesis were investigated at the molecular level. : 4-Nitroquinoline N-oxide (4-NQO) was used to create an oral cancer model in animals. Wistar rats were divided into five groups: Control, NQO, Juglone, NQO+J, and NQO+J*. The control group received the basal diet and tap water throughout the experiment. The NQO group received 4-NQO for 8 weeks in drinking water only. The Juglone group was administered intraperitoneally in a juglone solution for 10 weeks (1 mg/kg/day). The NQO+J group received 4-NQO in drinking water for 8 weeks, starting 1 week after the cessation of 4-NQO treatment. They were then administered intraperitoneally in a juglone solution for 10 weeks. (1 mg/kg/day). NQO+J* group: received 4 NQO for 8 weeks in drinking water and administered intraperitoneally in a juglone solution for 10 weeks (1 mg/kg/day). They were sacrificed at the end of the 22-week experimental period. The tongue tissues of the rats were isolated after the experiment, morphological changes were investigated by histological examinations, and the molecular apoptotic process was investigated by rt-qPCR and western blot. : Histological results indicate that tumors are formed in the tongue tissue with 4-NQO, and juglone treatment largely corrects the epithelial changes that developed with 4-NQO. It has been determined that apoptotic factors p53, Bax, and caspases are induced by the effect of juglone, while antiapoptotic factors such as Bcl-2 are suppressed. However, it was observed that the positive effects were more pronounced in rats given juglone together with 4-NQO. : The use of PIN1 inhibitors such as juglone in place of existing therapeutic approaches might be a promising and novel approach to the preservation and treatment of oral cancer and carcinogenesis. However, further research is required to investigate the practical application of such inhibitors.
: PIN1 在多种人类癌症中过表达，包括前列腺癌、乳腺癌和口腔鳞状细胞癌。胡桃醌（J）来源于核桃，据报道可通过修饰其巯基选择性抑制 PIN1。在这项研究中，在分子水平上研究了胡桃醌（也称为 PIN1 抑制剂）对口腔癌和癌变的潜在影响。 : 4-硝基喹啉 N-氧化物（4-NQO）用于在动物中创建口腔癌模型。Wistar 大鼠分为五组：对照组、NQO 组、胡桃醌组、NQO+J 组和 NQO+J组。对照组在整个实验过程中接受基础饮食和自来水。NQO 组仅在饮用水中接受 4-NQO 8 周。胡桃醌组腹腔注射胡桃醌溶液 10 周（1mg/kg/天）。NQO+J 组在饮用水中接受 4-NQO 8 周，在停止 4-NQO 治疗 1 周后开始，然后腹腔注射胡桃醌溶液 10 周（1mg/kg/天）。NQO+J组：在饮用水中接受 4-NQO 8 周，并腹腔注射胡桃醌溶液 10 周（1mg/kg/天）。他们在 22 周实验结束时被处死。实验结束后，分离大鼠的舌组织，通过组织学检查观察形态变化，通过 rt-qPCR 和 Western blot 检测分子凋亡过程。 : 组织学结果表明，4-NQO 在舌组织中形成肿瘤，胡桃醌治疗可显著纠正 4-NQO 引起的上皮变化。已确定凋亡因子 p53、Bax 和半胱天冬酶被胡桃醌的作用诱导，而抗凋亡因子如 Bcl-2 被抑制。然而，观察到在同时给予 4-NQO 和胡桃醌的大鼠中，阳性效应更为明显。 : 使用 PIN1 抑制剂（如胡桃醌）代替现有的治疗方法可能是一种有前途的新方法，可用于保存和治疗口腔癌和癌变。然而，需要进一步研究以调查此类抑制剂的实际应用。
