Bryophyllum pinnatum Induces p53-Dependent Apoptosis of Colorectal Cancer Cells via Increased Intracellular ROS and G2/M Cell-Cycle Arrest In Vitro and Validated in Silico by Molecular Docking

IF 3.3 3区 生物学 Q3 CELL BIOLOGY
Sumoyee Mukherjee, Sheuli Kangsa Banik, Sourio Chakraborty, Tanya Das, Manabendra Dutta Choudhury, Anusri Tripathi
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引用次数: 0

Abstract

Chemotherapy, radiotherapy and surgical treatments of cancer having several limitations and toxic side-effects, have led researchers to focus towards development of alternative natural plant-based therapeutics that can reduce disease severity. The present research work is mainly focussed towards identifying molecular mechanisms of apoptosis of colorectal cancer cells (HCT116) by perennial herb Bryophyllum pinnatum leaf-extract via both in vitro experimentations and in silico analysis. B. pinnatum leaf extract induced highest cytotoxicity at lowest dose (IC50:0.01 mg/mL) against HCT116 cells with 49.5% (p < 0.0001) cellular death, in comparison to other cancer cell lines. It has arrested HCT116 cell populations at G2/M cell-cycle phase and led to 10 folds (p < 0.0001) and 5.5 folds (p < 0.0001) increased intracellular ROS production in treated groups. ROS production might have led to significant 34.23% and 21.03% (p < 0.0001) apoptosis in treated cells, proved in vitro and in silico, with significant upregulation of p53 (p < 0.0001), BAX (p = 0.0252), CASPASE3 (p < 0.0001) and downregulation of BCL2 (p = 0.0058), leading to increased nuclear p53 (p = 0.0002) accumulation in treated cells, suggesting that the leaf-extract might have induced p53-dependent apoptosis of colorectal cancer cells. The phyto-extract also possess significant gene-modulatory potential as evident from qRT-PCR analysis of oncogenes and tumor suppressor genes. Leaf's bioactive phyto-constituents were elucidated by GC-MS and HPLC-ESI/MS analysis. In silico STITCH analysis provided significant network interactions between these bioactive phyto-compounds and studied proteins. Further Molecular Docking studies revealed strong binding between such docked complexes. Also, predicted major bioactive phyto-constituents of B. pinnatum leaf-extract such as Quercetin, Morin and β-Sitosterol have induced significant (p < 0.0001) apoptosis and increased intracellular ROS, validating their in silico interactions with studied proteins of HCT116 cells. All these studies together demonstrated ability of B. pinnatum to be used as a suitable natural phyto-therapeutic agent for development of chemo-preventive medications against colorectal cancer.

苔藓藓通过增加细胞内ROS和G2/M细胞周期阻滞诱导p53依赖性结直肠癌细胞凋亡,并通过分子对接在硅中验证。
由于癌症的化疗、放疗和手术治疗存在一些局限性和毒副作用,研究人员将重点放在开发可降低疾病严重程度的天然植物替代疗法上。本研究主要通过体外实验和芯片分析两种方法探讨多年生草本苔藓叶提取物对结直肠癌细胞(HCT116)凋亡的分子机制。最低剂量(IC50:0.01 mg/mL)时,滨荆叶提取物对HCT116细胞的毒性最高,为49.5% (p .0
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来源期刊
Cell Biology International
Cell Biology International 生物-细胞生物学
CiteScore
7.60
自引率
0.00%
发文量
208
审稿时长
1 months
期刊介绍: Each month, the journal publishes easy-to-assimilate, up-to-the minute reports of experimental findings by researchers using a wide range of the latest techniques. Promoting the aims of cell biologists worldwide, papers reporting on structure and function - especially where they relate to the physiology of the whole cell - are strongly encouraged. Molecular biology is welcome, as long as articles report findings that are seen in the wider context of cell biology. In covering all areas of the cell, the journal is both appealing and accessible to a broad audience. Authors whose papers do not appeal to cell biologists in general because their topic is too specialized (e.g. infectious microbes, protozoology) are recommended to send them to more relevant journals. Papers reporting whole animal studies or work more suited to a medical journal, e.g. histopathological studies or clinical immunology, are unlikely to be accepted, unless they are fully focused on some important cellular aspect. These last remarks extend particularly to papers on cancer. Unless firmly based on some deeper cellular or molecular biological principle, papers that are highly specialized in this field, with limited appeal to cell biologists at large, should be directed towards journals devoted to cancer, there being very many from which to choose.
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