Investigating the combinatory effect of Sclerocarya birrea with doxorubicin against selected colorectal cancer cell lines.

IF 2 Q3 PHARMACOLOGY & PHARMACY Drug Target Insights Pub Date : 2024-12-11 eCollection Date: 2024-01-01 DOI:10.33393/dti.2024.3219
Thembelihle H Nxasana, Innocensia M Mangoato, Patriciah M Masiu, Abhay P Mishra, Motlalepula G Matsabisa
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Abstract

Introduction: Colorectal cancer incidences continue to increase annually, worldwide. Herbal plants with antiproliferative properties received research interest as agents that can be adjuvant therapies with chemotherapy drugs to enhance their efficacy and reverse drug resistance.

Methods: Sclerocarya birrea ethanolic (SBE) and aqueous (SBW) extracts combined with doxorubicin (DOX) against drug-sensitive and drug-resistant colorectal cancer cells were investigated for their potential adjuvant and drug resistance reversal. The extracts were assessed for their potential anticancer activities on HCT15 and HT29 cell lines as well as their doxorubicin potentiating and drug resistance reversal effects respectively. The extracts were assessed for their cytotoxicity on normal 3T3-L1 fibroblast cells.

Results: Both SBE and SBW extracts exhibited no toxicity against normal 3T3 cells and showed low activity on the HT29 cell line. Contrarily, resistant HCT15 cells showed moderate to low activity with significantly higher inhibitory concentration (IC)50 values. The combination of SBE with DOX and SBW with DOX resulted in antagonistic interactions, causing an increase in IC50 values for HT29 and HCT15 cells. In contrast, the combination of DOX and verapamil (VER) produced an additive effect, with no change in their IC50 values.

Conclusion: Based on the findings from the combination treatment, the SBE and SBW extracts demonstrated higher efficacy and synergistic effects combined with DOX at IC75 compared to the combination of DOX and VER, suggesting their potential as anticancer agents. However, further research on both the SBE and SBW extracts' mechanisms of action and in vivo effects is warranted.

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研究 Sclerocarya birrea 与多柔比星对特定结直肠癌细胞株的联合作用。
导言:全球结直肠癌发病率逐年上升。具有抗增殖特性的草本植物作为化疗药物的辅助疗法,可增强化疗药物的疗效并逆转耐药性,因此受到了研究人员的关注:方法:研究了硬骨蕨乙醇提取物(SBE)和水提取物(SBW)与多柔比星(DOX)联合使用对药物敏感和耐药的结直肠癌细胞进行辅助治疗和逆转耐药性的潜力。分别评估了这些提取物对 HCT15 和 HT29 细胞系的潜在抗癌活性,以及它们对多柔比星的增效作用和耐药性逆转作用。还评估了提取物对正常 3T3-L1 成纤维细胞的细胞毒性:结果:SBE 和 SBW 提取物对正常 3T3 细胞无毒性,对 HT29 细胞系活性较低。相反,耐药的 HCT15 细胞则表现出中度到低度的活性,抑制浓度 (IC)50 值明显较高。SBE 与 DOX 以及 SBW 与 DOX 联用会产生拮抗作用,导致 HT29 和 HCT15 细胞的 IC50 值升高。相比之下,DOX 与维拉帕米(VER)的组合产生了相加效应,其 IC50 值没有变化:结论:根据联合治疗的结果,与 DOX 和 VER 联合治疗相比,SBE 和 SBW 提取物与 DOX 联合治疗的 IC75 值具有更高的疗效和协同作用,这表明它们具有作为抗癌药物的潜力。不过,还需要进一步研究 SBBE 和 SBW 提取物的作用机制和体内效应。
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来源期刊
Drug Target Insights
Drug Target Insights PHARMACOLOGY & PHARMACY-
CiteScore
2.70
自引率
0.00%
发文量
5
审稿时长
8 weeks
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