Octyl Gallate和Gallic Acid从贝利亚终末孢中分离出来,通过增强内在的细胞凋亡信号通路和提高抗氧化酶的水平来避免乳腺癌的进展。
Octyl Gallate and Gallic Acid Isolated from Terminalia bellirica Circumvent Breast Cancer Progression by Enhancing the Intrinsic Apoptotic Signaling Pathway and Elevating the Levels of Anti-oxidant Enzymes.
发表日期:2023 Mar 29
作者:
Periyasamy Vijayalakshmi, Sabapathy Indu, Christopher Ireen, Reji Manjunathan, Manikkam Rajalakshmi
来源:
ANTIOXIDANTS & REDOX SIGNALING
摘要:
探索新策略、寻找价格更为便宜的新型化学预防癌症药物,以抑制乳腺癌的进展,已成为当务之急。因此,本研究旨在评估从贝利柯( Terminalia bellirica)中提取的辛酸没食子酸酯(OG)和没食子酸(GA)在乳腺癌细胞株和DMBA诱导的斯普鲁格-道利大鼠动物模型中的抗癌功效。Western blot分析结果显示,在MCF-7和MDA-MB-231细胞株中,抗凋亡蛋白(Bcl-2和Bcl-xL)的表达显著下调(P<0.05),而促凋亡蛋白(Bak和Bax)的表达上调。研究发现,给予OG(20mg/kg体重)和GA(20mg/kg体重)的DMBA诱导的斯普鲁格-道利大鼠(50-55天龄)经过14周的治疗后,体重变化和血液学指标得到正常化,并且在血清中观察到肿瘤标志物癌胚抗原(CEA)、癌抗原15.3(CA 15.3)和氧化应激(TBARS)显著降低,而乳腺组织中抗氧化酶(SOD、CAT和GPx)水平的活性恢复到正常水平。计算分子相互作用研究也进行了以支持在体外获得的结果。组织组检查表明OG和GA的治疗作用。本研究揭示了OG和GA通过内在凋亡信号转导途径发挥其化学预防癌症作用的分子机制。由于OG和GA都具有防止乳腺癌进展的能力,因此可以进一步探索它们作为化疗天然药物的潜力。©2023年,版权所有作者,独家许可Springer Science+Business Media,LLC的一部分,属于Springer Nature。
Exploration of new strategies and identification of less expensive novel chemoprevention agents against breast cancer progression have become the need of the hour. Thus, the present study aimed at evaluating the anti-cancer efficacies of octyl gallate (OG) and gallic acid (GA) isolated from Terminalia bellirica (T. bellirica) in breast cancer cell lines and DMBA-induced Sprague-Dawley animal model. The results of western blot analysis show significant (p < 0.05) downregulation of anti-apoptotic protein (Bcl-2 and Bcl-xL) expression and up-regulation of pro-apoptotic protein (Bak and Bax) expression in both MCF-7 and MDA-MB-231 cell lines. Our findings also show that DMBA-induced Sprague-Dawley rats (50-55 days old) orally administered with OG (20 mg/kg body wt.) and GA (20 mg/kg body wt.) for a treatment period of 14 weeks were observed for normalized body weight changes and hematological indices and significant reduction of tumor markers carcinoembryonic antigen (CEA), cancer antigen 15.3 (CA 15.3), and oxidative stress (TBARS) in serum, while the activity of anti-oxidant enzyme (SOD, CAT, and GPx) levels estimated in the mammary tissue was found restored back to normal. Computational molecular interaction study was also performed to substantiate the in vitro obtained results. The tissue histology reveals the therapeutic role of OG and GA. The study conducted brings to limelight of the molecular mechanisms of intrinsic apoptotic signaling pathway through which OG and GA exert their chemopreventive action. Both OG and GA can be explored further as chemotherapeutic natural drugs for their ability to prevent breast cancer progression.© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.