Tarawneh Noor, Hamadneh Lama, Alshaer Walhan, Al Bawab Abdel Qader, Bustanji Yasser, Abdalla Shtaywy
Department of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University, Amman, 11733, Jordan.
Department of Basic Medical Sciences, Al-Balqa Applied University, Al-Salt, 19117, Jordan.
Heliyon. 2024 Oct 15;10(20):e39402. doi: 10.1016/j.heliyon.2024.e39402. eCollection 2024 Oct 30.
Scutellarein has an anticancer potential, but the pathway of its action has not been elucidated. This study investigated scutellarein efficacy against human colorectal cancer (CRC) and explored the possible pathway of its action. MTT assay was employed to detect scutellarein effect on HT-29, SW-480, and HCT116 cells viability. Scutellarein impact on programmed cell death was studied by Annexin V-FITC/PI and its role on migration and invasion was detected by wound healing and transwell chambers. Aquaporin (AQP) 1, 3, and 5 expression before and after scutellarein treatment was approached by quantitative polymerase chain reaction (RT‒qPCR) and immunostaining while Western blotting was used to explore scutellarein effect on PI3K/AKT pathway. Scutellarein induced apoptosis and necrosis in CRC cells, thus inhibiting proliferation, migration, and invasion. Colon cancer cells exhibited positive staining for AQP 1, 3, and 5 which was downregulated by scutellarein. PI3K/AKT pathway mediating cell proliferation and growth was also modulated by scutellarein; phosphatase and tensin (PTEN) was upregulated, whereas PI3K, AKT, and p-AKT expressions were downregulated, and the downstream mTOR and phosphorylated mTOR were also suppressed at the protein level. Data indicated that scutellarein suppressed growth, migration as well as invasion of these CRC cells by downregulating the expression of , , and and upregulating where the latter inhibited the genes and the proteins involved in pathway. The data indicate that scutellarein is a promising therapeutic agent that inhibits growth, migration, and invasion of CRC cells by down-regulating the expression of AQP 1, 3, and 5 and by PTEN up-regulation, thus inhibiting PI3K/AKT. These molecular alterations represent potential prognostic biomarkers for the metastasis of colon cancer, where the down-regulation of AQPs enhances patient survival.
野黄芩苷具有抗癌潜力，但其作用途径尚未阐明。本研究调查了野黄芩苷对人结直肠癌（CRC）的疗效，并探索了其可能的作用途径。采用MTT法检测野黄芩苷对HT-29、SW-480和HCT116细胞活力的影响。通过Annexin V-FITC/PI研究野黄芩苷对程序性细胞死亡的影响，通过伤口愈合实验和Transwell小室检测其对迁移和侵袭的作用。采用定量聚合酶链反应（RT-qPCR）和免疫染色检测野黄芩苷处理前后水通道蛋白（AQP）1、3和5的表达，同时用蛋白质印迹法探索野黄芩苷对PI3K/AKT通路的影响。野黄芩苷诱导CRC细胞凋亡和坏死，从而抑制其增殖、迁移和侵袭。结肠癌细胞对AQP 1、3和5呈阳性染色，野黄芩苷可使其下调。介导细胞增殖和生长的PI3K/AKT通路也受到野黄芩苷的调节；磷酸酶和张力蛋白同源物（PTEN）上调，而PI3K、AKT和p-AKT的表达下调，下游的mTOR和磷酸化mTOR在蛋白水平也受到抑制。数据表明，野黄芩苷通过下调AQP 1、3和5的表达以及上调PTEN来抑制这些CRC细胞的生长、迁移和侵袭，其中PTEN抑制PI3K/AKT通路中的基因和蛋白质。数据表明，野黄芩苷是一种有前景的治疗药物，它通过下调AQP 1、3和5的表达以及上调PTEN来抑制CRC细胞的生长、迁移和侵袭，从而抑制PI3K/AKT通路。这些分子改变代表了结肠癌转移的潜在预后生物标志物，其中AQPs的下调可提高患者生存率。
