Zoology Department, Faculty of Science, Port Said University, Port Said, Egypt.
Botany Department, Faculty of Science, Port Said University, Port Said, Egypt.
J Biomol Struct Dyn. 2023 Jan;41(1):147-160. doi: 10.1080/07391102.2021.2004231. Epub 2021 Dec 2.
ssp (Wild.) Nyman is growing with dimorphic leaf forms (entire or pinnatifid lamina) along the Mediterranean coast of Egypt. The cytotoxic activities of dried shoot systems of the two morphological forms were evaluated by testing and comparing the effects of ethanolic and aqueous extracts on the viability of five human cell lines. GC-MS analysis was performed to identify the bioactive and anticancer compounds present in the most active extracts. MTT assay indicated that both aqueous and ethanolic extracts have selective cytotoxic activities against cancer cell lines with no inhibitory activities against normal Wi38 or Vero cell lines. The underlying mechanism of cytotoxicity involved the induction of G2/M phase arrest in targeted cells MCF-7 and HCT-116 associated with inducing apoptosis in both cell lines, as indicated by Annexin-V assay. Apoptosis investigation in MCF-7 and HCT-116 cells treated with ethanolic extracts, was further investigated through RT-PCR, which exhibited elevation of proapoptotic genes of P53, BAX, Capase-3,6,7,8,9, and downregulation of antiapoptotic gene (BCL-2) upon treatment. The GC-MS analysis of ethanolic extracts of pinnatifid and entire forms revealed the existence of 18 and 13 compounds, respectively, with eleven compounds that were detected in pinnatifid form only and seven compounds were identified exclusively in the entire form. Molecular Docking study revealed that the identified compounds exhibited good binding affinity towards BCL-2 inhibition, and this agreed with the suggested apoptotic mechanism. To the best of authors' knowledge, this is the first scientific evidence underline the variability in the chemical composition associated with variable anticancer activities of dimorphic forms of Communicated by Ramaswamy H. Sarma.
ssp(野生)Nyman 在地中海沿岸的埃及生长,具有二态叶形(全缘或具羽状裂片的叶片)。通过测试和比较两种形态的乙醇和水提取物对五种人类细胞系活力的影响,评估了干茎系统的细胞毒性活性。进行 GC-MS 分析以鉴定存在于最活跃提取物中的生物活性和抗癌化合物。MTT 测定表明,水提物和醇提物均对癌细胞系具有选择性细胞毒性活性,对正常 Wi38 或 Vero 细胞系无抑制活性。细胞毒性的潜在机制涉及在靶向细胞 MCF-7 和 HCT-116 中诱导 G2/M 期阻滞,与两种细胞系中的细胞凋亡有关,如 Annexin-V 测定所示。用乙醇提取物处理 MCF-7 和 HCT-116 细胞后的凋亡研究通过 RT-PCR 进一步研究,结果显示在处理后,促凋亡基因 P53、BAX、Capase-3、6、7、8、9 的表达升高,抗凋亡基因(BCL-2)的表达下调。对羽状和全缘形式的乙醇提取物的 GC-MS 分析表明,分别存在 18 种和 13 种化合物,其中 11 种化合物仅在羽状形式中检测到,7 种化合物仅在全缘形式中鉴定到。分子对接研究表明,鉴定出的化合物对 BCL-2 抑制表现出良好的结合亲和力,这与所提出的凋亡机制一致。据作者所知,这是第一个科学证据,证明二态形式的化学组成的可变性与可变的抗癌活性有关。由 Ramaswamy H. Sarma 通讯。