Aggarwal Sadhna, Bhadana Kanchan, Singh Baldeep, Rawat Meenakshi, Mohammad Taj, Al-Keridis Lamya Ahmed, Alshammari Nawaf, Hassan Md Imtaiyaz, Das Satya N
Department of Biotechnology, All India Institute of Medical Sciences, New Delhi, India.
Center for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, India.
Front Pharmacol. 2022 Jun 2;13:918479. doi: 10.3389/fphar.2022.918479. eCollection 2022.
is a tropical plant with traditional medicinal significance that possesses antimicrobial, antifungal, anti-parasitic, and anti-tumor properties. Here, we have elucidated the anti-tumor effects of extract (CZE) and its bioactive compound cinnamaldehyde (CIN) on oral cancer and elucidated underlying molecular mechanisms. Anti-tumor activities of CZE and CIN were demonstrated by various experiments on oral cancer cells (SCC-4, SCC-9, SCC-25). The cell proliferation, growth, cell cycle arrest, apoptosis, and autophagy were analyzed by MTT, clonogenic assay, propidium iodide, annexin-V-PI, DAPI, and acridine orange staining, respectively. The binding affinity of CIN towards dihydrofolate reductase and p38-MAP kinase alpha was analyzed by molecular docking. Western blot assay was performed to assess the alteration in the expression of various proteins. CZE and CIN treatment significantly inhibited the growth and proliferation of oral cancer cells in a dose-dependent manner. These treatments further induced apoptosis, cell cycle arrest, and autophagy. CZE and CIN inhibited the invasion and cytoplasmic translocation of NF-κB in these cell lines. CIN showed a high affinity to MAP kinase P38 alpha and dihydrofolate reductase with binding affinities of -6.8 and -5.9 kcal/mol, respectively. The cancer cells showed a decreased expression of various PI3k-AKT-mTOR pathways related to VEGF, COX-2, Bcl-2, NF-κB, and proteins post-treatment.
是一种具有传统医学意义的热带植物，具有抗菌、抗真菌、抗寄生虫和抗肿瘤特性。在此，我们阐明了提取物（CZE）及其生物活性化合物肉桂醛（CIN）对口腔癌的抗肿瘤作用，并阐明了潜在的分子机制。通过对口腔癌细胞（SCC - 4、SCC - 9、SCC - 25）进行的各种实验证明了CZE和CIN的抗肿瘤活性。分别通过MTT法、克隆形成试验、碘化丙啶、膜联蛋白 - V - PI、DAPI和吖啶橙染色分析细胞增殖、生长、细胞周期阻滞、凋亡和自噬。通过分子对接分析CIN对二氢叶酸还原酶和p38 - MAP激酶α的结合亲和力。进行蛋白质印迹分析以评估各种蛋白质表达的变化。CZE和CIN处理以剂量依赖性方式显著抑制口腔癌细胞的生长和增殖。这些处理进一步诱导凋亡、细胞周期阻滞和自噬。CZE和CIN抑制这些细胞系中NF - κB的侵袭和细胞质转位。CIN对MAP激酶P38α和二氢叶酸还原酶显示出高亲和力，结合亲和力分别为 - 6.8和 - 5.9千卡/摩尔。处理后，癌细胞中与VEGF、COX - 2、Bcl - 2、NF - κB相关的各种PI3k - AKT - mTOR途径的蛋白质表达降低。
