Department of Biology, Faculty of Science, Al-Baha University, Al-Baha, Saudi Arabia.
Anticancer Agents Med Chem. 2024;24(15):1097-1108. doi: 10.2174/0118715206288807240527165444.
Globally, colorectal cancer (CRC) is categorized as the third type of cancer associated with mortalities. Chemotherapeutic drugs such as cisplatin can be used to treat cancer-affected patients. However, several adverse effects are associated with its application. This motivated the researchers to search for alternatives that are more efficient and have fewer undesirable effects. Kolaviron is a bioflavonoid that has been reported to have antioxidant and anti-inflammatory properties.
This study aimed to compare the anticancer effects of kolaviron and cisplatin on Caco-2 cells. The IC of kolaviron and cisplatin were calculated, and redox status, apoptotic-related proteins and the cell cycle were also examined.
Caco-2 cells were treated with kolaviron ( ⅓, and ½ of IC dose) and cisplatin (IC dose) for 24 h and 48 h. Cell viability was assessed using the MTT protocol. Redox status and apoptotic-related proteins, in addition to the cell cycle, were examined.
The MTT assay showed the IC of kolaviron is 9.49 μg/mL, and that of cisplatin is 2.71 μg/ml against Caco-2 cells. Further, both doses of kolaviron significantly increased the leakage of lactate dehydrogenase (LDH), the production of reactive oxygen species (ROS), and lipoperoxidation (LPO), besides decreasing the antioxidant potency of tumor cells as revealed by the diminished reduced glutathione (GSH). At the molecular level, a significant increase in the levels of p53, cytochrome c, Bax, and caspase 3 was recorded, coupled with a decrease in the level of Bcl2, after treating the Caco-2 cells with kolaviron and cisplatin. Furthermore, kolaviron demonstrated asserted more effects on apoptosis and increased cell percentage in the subG1 phase. In addition, a notable decrease in the expression of proliferating cell nuclear antigen (PCNA) and cyclin D1 is associated with an increase in the expression of tumor protein P53 (TP53) in kolaviron-treated Caco-2 cells cancerous cells.
Conclusively, these data suggest that kolaviron has a potential antitumor capacity against colorectal cancer via multiple pathways, including enhancement of ROS production, redox status, p53 pathway, and apoptosis. Therefore, this study authenticated the capability of kolaviron as a valuable chemotherapeutic agent.
在全球范围内,结直肠癌(CRC)是死亡率排名第三的癌症类型。顺铂等化疗药物可用于治疗癌症患者。然而,其应用存在多种不良反应。这促使研究人员寻找更有效且不良反应更少的替代药物。Kolaviron 是一种生物类黄酮,已被报道具有抗氧化和抗炎特性。
本研究旨在比较 kolaviron 和顺铂对 Caco-2 细胞的抗癌作用。计算 kolaviron 和顺铂的 IC,并检测氧化还原状态、凋亡相关蛋白和细胞周期。
用 kolaviron(IC 剂量的 1/3 和 1/2)和 cisplatin(IC 剂量)处理 Caco-2 细胞 24 小时和 48 小时。使用 MTT 法评估细胞活力。检测氧化还原状态和凋亡相关蛋白以及细胞周期。
MTT 测定显示 kolaviron 的 IC 为 9.49 μg/mL,顺铂的 IC 为 2.71 μg/ml 对 Caco-2 细胞。此外,两种剂量的 kolaviron 均显著增加了乳酸脱氢酶(LDH)的漏出、活性氧(ROS)的产生和脂质过氧化(LPO),同时降低了肿瘤细胞的抗氧化能力,表现为还原型谷胱甘肽(GSH)减少。在分子水平上,用 kolaviron 和 cisplatin 处理 Caco-2 细胞后,p53、细胞色素 c、Bax 和 caspase 3 的水平显著升高,而 Bcl2 的水平降低。此外,kolaviron 对细胞凋亡的作用更为明显,并增加了 subG1 期的细胞百分比。此外,在 kolaviron 处理的 Caco-2 癌细胞中,增殖细胞核抗原(PCNA)和细胞周期蛋白 D1 的表达显著降低,而肿瘤蛋白 P53(TP53)的表达增加。
总之,这些数据表明,kolaviron 通过多种途径具有抑制结直肠癌细胞生长的潜力,包括增强 ROS 产生、氧化还原状态、p53 途径和细胞凋亡。因此,本研究证实了 kolaviron 作为一种有价值的化疗药物的能力。