Centre de recherche cellulaire et moléculaire appliquée, université des sciences médicales de Kerman, Kerman, Iran.
Centre de recherche en physiologie, institut de neuropharmacologie, université des sciences médicales de Kerman, Kerman, Iran.
Ann Pharm Fr. 2024 Jun;82(4):685-697. doi: 10.1016/j.pharma.2024.02.013. Epub 2024 Feb 24.
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.
结直肠癌（CRC）是全球第二大癌症相关死亡原因，化疗作为 CRC 治疗的重要组成部分，存在一些缺点，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。藏药瑞香狼毒（R. khorasanicum）是一种含有高黄酮、白藜芦醇和蒽醌的药用植物，因此它可能是抗氧化剂的潜在来源，可用于治疗目的，并在癌细胞中引发细胞凋亡。在这项研究中，我们研究了瑞香狼毒根水醇提取物处理对诱导 HT-29 和 Caco-2 人结直肠腺癌细胞线粒体凋亡的影响。首先，测定总酚和类黄酮的含量。然后，通过 MTT 测定法评估瑞香狼毒对三种不同类型细胞的细胞毒性作用，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，进行了流式细胞术和蛋白质印迹分析。本研究结果表明，瑞香狼毒含有丰富的酚类（356.4±9.4 GAE/gDW）和类黄酮（934.55±17.1 QE/gDW）。MTT 检测结果表明，浓度为 100、60 和 30μg/mL 的瑞香狼毒显著降低 HT-29 和 Caco-2 细胞系中的细胞活力（P<0.05）。研究还表明，瑞香狼毒提取物在这些细胞系中诱导细胞凋亡而不是坏死。此外，Bcl-2 的表达在 HT-29 和 Caco-2 细胞系中显著降低，而 Bax 和 cleaved caspase-3 的表达在瑞香狼毒处理组中显著增加（P<0.05）。综上所述，我们的研究结果表明，瑞香狼毒根提取物中高含量的酚类和类黄酮可能在 HT-29 和 Caco-2 结肠癌细胞的细胞毒性和细胞凋亡诱导中发挥重要作用。
