Thozhukkad Moosaripparambil Shiji, Vadakkadath Meethal Kannan
Department of Zoology, University of Calicut, Calicut University PO, Malappuram District, Kerala, 673635, India.
Centre for Advances in Molecular Biology, University of Calicut, Malappuram District, Kerala, 673635, India.
Sci Rep. 2025 Feb 3;15(1):4088. doi: 10.1038/s41598-025-88572-6.
Natural resources provide valuable medicinal components that are highly sought after as alternatives to synthetic drugs for treating serious diseases like cancer. Hewittia malabarica, a creeper native to India, is recognized for its exceptional medicinal properties. In this study, the anticancer property of different solvent extracts and composition of active extract from H. malabarica were examined. Of the extracts prepared using petroleum ether, chloroform, ethyl acetate, acetone, methanol and water, the chloroform extract showed the highest cytotoxicity with an IC value of 31.97 ± 3.07 µg/mL towards HT29 cell line followed by petroleum ether extract with an IC value of 76.58 ± 4.74 µg/mL. These extracts were comparatively non-toxic to the normal human keratinocyte cell line, HaCaT, indicating its selective toxicity to cancerous cells. The cytomorphological changes associated with the chloroform extract and AO/EB dual staining indicated apoptotic cell death. An analysis of ADME properties of compounds obtained in GC-MS analysis of the chloroform extract showed that compounds such as Cyclododecanol, Sulfurous acid hexyl octyl ester, 2,4-Ditert-Butylphenol and 1,2-benzenedicarboxylic acid had favourable physicochemical and drug-likeness characteristics. When these compounds were docked on to Bax, Caspase-3 Caspase-9 and Cox-2, the proteins integral to the mitochondrial apoptotic pathway, using PyRX software, the docking score was in the range from - 4 to -6.9 kcal/mol. Particularly, 2,4-Ditert-Butylphenol showed the highest binding scores towards the selected targets. These results indicate that the mechanism of cytotoxicity observed may be mediated through induction of apoptosis in cancer cell lines. The identification of the active molecule/s in the chloroform extract will serve as drug candidate for colorectal carcinoma. Non-toxicity of the components in the extract towards normal cell line will make it selective sparing normal cells.
自然资源提供了有价值的药用成分，作为合成药物的替代品，这些成分在治疗癌症等严重疾病方面备受追捧。原产于印度的攀缘植物马拉巴赫维提亚（Hewittia malabarica）因其卓越的药用特性而闻名。在本研究中，对马拉巴赫维提亚不同溶剂提取物的抗癌特性以及活性提取物的成分进行了研究。在用石油醚、氯仿、乙酸乙酯、丙酮、甲醇和水制备的提取物中，氯仿提取物对HT29细胞系显示出最高的细胞毒性，IC值为31.97±3.07μg/mL，其次是石油醚提取物，IC值为76.58±4.74μg/mL。这些提取物对正常人角质形成细胞系HaCaT相对无毒，表明其对癌细胞具有选择性毒性。与氯仿提取物相关的细胞形态学变化和AO/EB双重染色表明细胞凋亡死亡。对氯仿提取物进行GC-MS分析得到的化合物的ADME性质分析表明，环十二醇、己基辛基亚硫酸酯、2,4-二叔丁基苯酚和1,2-苯二甲酸等化合物具有良好的物理化学和类药特性。当使用PyRX软件将这些化合物对接至线粒体凋亡途径不可或缺的蛋白质Bax、Caspase-3、Caspase-9和Cox-2时，对接分数在-4至-6.9kcal/mol范围内。特别是，2,4-二叔丁基苯酚对所选靶点显示出最高的结合分数。这些结果表明，观察到的细胞毒性机制可能是通过诱导癌细胞系凋亡来介导的。氯仿提取物中活性分子的鉴定将作为结直肠癌的候选药物。提取物中的成分对正常细胞系无毒，将使其选择性地保护正常细胞。
