关键词: Apoptose Apoptosis CaCo-2 Caco-2 Cancer colorectal Colorectal cancer HT-29 Rheum khorasanicum

Mesh : Humans Plant Extracts / pharmacology Caco-2 Cells Colorectal Neoplasms / drug therapy pathology Adenocarcinoma / drug therapy pathology HT29 Cells Rheum / chemistry Apoptosis / drug effects Plant Roots / chemistry Flavonoids / pharmacology Animals Antineoplastic Agents, Phytogenic / pharmacology Mice Cell Survival / drug effects Phenols / pharmacology Computer Simulation Ethanol

来  源:   DOI:10.1016/j.pharma.2024.02.013

Abstract:
Colorectal cancer (CRC) is the second greatest cause of cancer-related death in the world and chemotherapy, as an important part of CRC treatment, has some drawbacks, including systemic toxicity. Therefore, it is crucial to discover new and more effective CRC treatment plans. Rheum khorasanicum (R. khorasanicum) is a medicinal plant with high flavonoids, stilbenes, and anthraquinone contents, so it can be a potential source of antioxidants and can be used for therapeutic purposes and trigger apoptosis in cancer cells. In this study, we investigated the effects of hydroalcoholic root extract of R. khorasanicum treatment on inducing mitochondrial apoptosis of HT-29 and Caco-2 human colorectal adenocarcinoma cells. Firstly, the total phenolic and flavonoid content was determined. Then, the cytotoxic effects of R. khorasanicum on cells of three different types, including HT-29 and Caco-2 colon cancer cells as well as normal 3T3 cells were assessed using the MTT assay. To investigate the characteristics of cellular death, flow cytometry, and western blotting were performed. The results of this study indicated considerable phenolic (356.4±9.4 GAE/gDW) and flavonoid (934.55±17.1 QE/gDW) contents in R. khorasanicum. MTT assay\'s finding indicated that 100, 60, and 30μg/mL concentrations of R. khorasanicum reduce cell viability in HT-29 and Caco-2 cell lines significantly (P<0.05). It has been also revealed that R. khorasanicum extract induces apoptosis rather than necrosis in these cell lines. Moreover, Bcl-2 expression was significantly reduced in both HT-29 and Caco-2 cell lines, while Bax and cleaved caspase-3 expression soared considerably in the groups under R. khorasanicum treatment (P<0.05). In conclusion, our findings have suggested that high phenol and flavonoid contents of R. khorasanicum root extract possibly play an important role in cell cytotoxicity and apoptosis induction in HT-29 and Caco-2 colon cancer cells.
摘要:
结直肠癌(CRC)是世界上癌症相关死亡的第二大原因,化疗,作为CRC治疗的重要组成部分,有一些缺点,包括全身毒性。因此,发现新的更有效的CRC治疗方案至关重要.大黄(R.horasanicum)是一种具有高类黄酮的药用植物,二苯乙烯,和蒽醌含量,因此它可能是抗氧化剂的潜在来源,可用于治疗目的并引发癌细胞凋亡。在这项研究中,我们研究了罗氏酵母水醇根提取物对诱导HT-29和Caco-2人结直肠腺癌细胞线粒体凋亡的影响。首先,测定总酚和黄酮含量。然后,K.对三种不同类型细胞的细胞毒作用,使用MTT测定评估包括HT-29和Caco-2结肠癌细胞以及正常3T3细胞。为了研究细胞死亡的特征,流式细胞术,并进行了蛋白质印迹。这项研究的结果表明,呼罗兰中相当多的酚类(356.4±9.4GAE/gDW)和类黄酮(934.55±17.1QE/gDW)含量。MTT分析的发现表明,100、60和30µg/mL浓度的霍拉西氏菌可显著降低HT-29和Caco-2细胞系中的细胞活力(P<0.05)。还揭示了在这些细胞系中,罗氏菌提取物诱导细胞凋亡而不是坏死。此外,Bcl-2在HT-29和Caco-2细胞系中的表达显著降低,而Bax和裂解的caspase-3的表达在霍氏弧菌治疗下显著飙升(P<0.05)。总之,我们的研究结果表明,高含量的horasanicum根提取物可能在HT-29和Caco-2结肠癌细胞的细胞毒性和凋亡诱导中起重要作用。
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