Alanazi Jowaher, Unnisa Aziz, Alanazi Muteb, Alharby Tareq Nafea, Moin Afrasim, Rizvi Syed Mohd Danish, Hussain Talib, Awadelkareem Amir Mahgoub, Elkhalifa AbdElmoneim O, Faiyaz Syed Shah Mohammed, Khalid Mohammad, Gowda Devegowda Vishakante
Department of Pharmacology and Toxicology, College of Pharmacy, University of Ha'il, Ha'il 81442, Saudi Arabia.
Department of Pharmaceutical Chemistry, College of Pharmacy, University of Ha'il, Ha'il 81442, Saudi Arabia.
Pharmaceuticals (Basel). 2022 Nov 14;15(11):1410. doi: 10.3390/ph15111410.
Breast cancer represents the most frequently occurring cancer globally among women. As per the recent report of the World Health Organization (WHO), it was documented that by the end of the year 2020, approximately 7.8 million females were positively diagnosed with breast cancer and in 2020 alone, 685,000 casualties were documented due to breast cancer. The use of standard chemotherapeutics includes the frontline treatment option for patients; however, the concomitant side effects represent a major obstacle for their usage. Carbazole alkaloids are one such group of naturally-occurring bioactive compounds belonging to the Rutaceae family. Among the various carbazole alkaloids, 3-Methoxy carbazole or C13H11NO (MHC) is obtained from Clausena heptaphylla as well as from Clausena indica. In this study, MHC was investigated for its anti-breast cancer activity based on molecular interactions with specific proteins related to breast cancer, where the MHC had predicted binding affinities for NF-κB with −8.3 kcal/mol. Furthermore, to evaluate the biological activity of MHC, we studied its in vitro cytotoxic effects on MCF-7 cells. This alkaloid showed significant inhibitory effects and induced apoptosis, as evidenced by enhanced caspase activities and the cellular generation of ROS. It was observed that a treatment with MHC inhibited the gene expression of NF-kB in MCF-7 breast cancer cells. These results suggest that MHC could be a promising medical plant for breast cancer treatment. Further studies are needed to understand the molecular mechanisms behind the anticancer action of MHC.
乳腺癌是全球女性中最常见的癌症。根据世界卫生组织（WHO）的最新报告，据记载，到2020年底，约有780万女性被确诊患有乳腺癌，仅在2020年，就有68.5万人因乳腺癌死亡。标准化疗药物的使用是患者的一线治疗选择；然而，随之而来的副作用是其使用的主要障碍。咔唑生物碱是属于芸香科的一类天然存在的生物活性化合物。在各种咔唑生物碱中，3-甲氧基咔唑或C13H11NO（MHC）可从七叶吴茱萸和印度吴茱萸中获得。在本研究中，基于MHC与乳腺癌相关特定蛋白的分子相互作用，对其抗乳腺癌活性进行了研究，其中MHC对NF-κB的预测结合亲和力为−8.3 kcal/mol。此外，为了评估MHC的生物活性，我们研究了其对MCF-7细胞的体外细胞毒性作用。这种生物碱显示出显著的抑制作用并诱导细胞凋亡，这通过增强的半胱天冬酶活性和细胞内ROS的产生得到证明。观察到用MHC处理可抑制MCF-7乳腺癌细胞中NF-κB的基因表达。这些结果表明，MHC可能是一种有前途的用于治疗乳腺癌的药用植物。需要进一步研究以了解MHC抗癌作用背后的分子机制。
