关键词: AL, aqueous extract of A. hierochuntica’s leaf ASD, aqueous extract of A. hierochuntica’s seed AST, aqueous extract of A. hierochuntica’s stem Anastatica hierochuntica Apoptosis BC, breast cancer Breast cancer CDK, cyclin-dependent kinase Cell cycle MCF-7, Michigan Cancer Foundation-7 ML, methanolic extract of A. hierochuntica’s leaf MSD, methanolic extract of A. hierochuntica’s seed MST, methanolic extract of A. hierochuntica’s stem NP40, Nonidet P-40 Natural products P53 STS, Staurosporine TP53, tumor protein p53

来  源:   DOI:10.1016/j.jsps.2020.06.020   PDF(Sci-hub)   PDF(Pubmed)

Abstract:
Breast cancer therapy using anticancer bioactive compounds derived from natural products as adjuvant treatment has gained recognition due to expensive and toxic conventional chemotherapeutic drugs. The whole plant of Anastatica hierochuntica (L.) (A. hierochuntica) has been investigated for its pharmacologically important anticancer properties but without categorizing the biological activities of the plant parts. We assessed the anticancer potential of different parts of A. hierochuntica (seeds, stems and leaves) and explored their mechanisms of action using the human breast cancer cell line, MCF-7. Currently, we investigated the antiproliferative effects of methanolic (MSD, MST, ML) and aqueous (ASD, AST, AL) extracts of A. hierochuntica plant parts on the MCF-7 cells using cell viability assays. Flow cytometry, Western Blot, DNA fragmentation, and gene expression assays were performed to evaluate apoptosis and cell cycle regulatory proteins. The results indicate that the methanolic and aqueous extracts decreased MCF-7 cell viability in a dose-dependent manner. The induction of apoptosis was observed in all the methanolic and aqueous-treated MCF-7 cells. The cell death process was confirmed by the visualization of DNA fragmentation and cleavage of the intrinsic apoptotic pathways, caspase-9 and caspase-3, the key enzyme causing apoptosis hallmarks. In addition, the most pro-apoptotic extracts, ASD and ML, up-regulated the expression of pro-apoptotic Bax, tumor suppressor TP53 genes and the cyclin inhibitor CDKN1A gene. In conclusion, of the aqueous and methanolic extracts of A. hierochuntica plant parts exerting antiproliferative effects through the induction of apoptosis in breast cancer MCF-7 cells, ASD and ML extracts were the most promising natural-based drugs for the treatment of breast cancer.
摘要:
由于昂贵且有毒的常规化疗药物,使用源自天然产物的抗癌生物活性化合物作为辅助治疗的乳腺癌治疗已获得认可。Anastaticahierochuntica的整个植物(L.)(A.hierochuntica)已因其药理学上重要的抗癌特性而受到研究,但未对植物部分的生物活性进行分类。我们评估了A.hierochuntica不同部位的抗癌潜力(种子,茎和叶),并使用人类乳腺癌细胞系探索其作用机制,MCF-7.目前,我们研究了甲醇(MSD,MST,ML)和水性(ASD,AST,AL)使用细胞活力测定对MCF-7细胞上的A.hierochuntica植物部分的提取物。流式细胞术,西方印迹,DNA片段化,和基因表达测定来评估细胞凋亡和细胞周期调控蛋白。结果表明甲醇和水提取物以剂量依赖性方式降低MCF-7细胞活力。在所有甲醇和水性处理的MCF-7细胞中观察到细胞凋亡的诱导。通过DNA片段化和内在凋亡途径的裂解的可视化证实了细胞死亡过程,caspase-9和caspase-3是引起细胞凋亡的关键酶。此外,最促凋亡的提取物,ASD和ML,上调促凋亡Bax的表达,肿瘤抑制基因TP53和细胞周期蛋白抑制剂CDKN1A基因。总之,A.hierochuntica植物部分的水性和甲醇提取物通过诱导乳腺癌MCF-7细胞凋亡而发挥抗增殖作用,ASD和ML提取物是治疗乳腺癌最有前途的天然药物。
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