Cannabis sativa L. Extracts can reverse drug resistance in colorectal carcinoma cells in vitro

Q2 Medicine Synergy Pub Date : 2019-12-01 DOI:10.1016/j.synres.2019.100056

Innocensia Mokgohlwe Mangoato, Chandrashekara Puthanapura Mahadevappa, Motlalepula Gilbert Matsabisa

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引用次数: 3

Abstract

Background

Multidrug resistance (MDR) to known chemotherapeutic agents is increasing while the development of new drugs is lacking behind. Combination therapies might increase the development of effective treatment. Anticancer properties of C. sativa L. have been extensively studied against various cancer cell lines but research on its effectiveness on MDR in cancer is less documented.

Aim

To determine the potential resistant reversal of the cytostatic drug doxorubicin by C. sativa L. extracts through combination studies.

Method

The cytotoxic effect of the different C. sativa L. extracts was assessed against a panel of human colon cancer cells (HT-29, Caco-2, HCT-15, LS513) and normal colon cells (CCD-18Co) by MTT assay. Drug-extract combination studies were performed on HCT-15 and LS513 MDR cells.

Results

DCM: methanol- and H₂O extracts moderately inhibited the growth in HCT-15 and LS513 cells (IC₅₀: 20–100 μg/ml). DCM- and H₂O extracts potently inhibited HT-29 cell growth. Higher concentrations (100 μg/ml) of the hexane- and DCM- extracts slightly stimulated growth in Caco-2 cells. All the C. sativa L. extracts were more cytotoxic towards the cancerous cells than towards the normal colon cells. Combination studies between doxorubicin and the C. sativa L. extracts revealed synergistic growth inhibitory effects (CI < 1). The sensitivity to doxorubicin increased in HCT-15 and LS513 cells by 2.08- to 74.07-fold and 2.21- to 300.7-fold, respectively, compared to verapamil which improved it by 1.41-fold and 0.05-fold, respectively.

Conclusion

C. sativa L. extracts possess direct selective cytotoxic effect on colon cells and have a potential to reverse doxorubicin resistance.

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大麻提取物可逆转结直肠癌细胞的耐药性

背景对已知化疗药物的多药耐药(MDR)呈上升趋势，而新药的开发相对滞后。联合治疗可能会促进有效治疗的发展。芥蓝的抗癌特性已被广泛研究，但其对癌症耐多药的疗效研究较少。目的通过联合研究确定芥蓝提取物对细胞抑制药物阿霉素的潜在耐药性逆转作用。方法采用MTT法测定不同提取物对人结肠癌细胞(HT-29、Caco-2、HCT-15、LS513)和正常结肠癌细胞(CCD-18Co)的细胞毒作用。在HCT-15和LS513 MDR细胞上进行药物-提取物联合研究。结果dcm:甲醇和水提取物对HCT-15和LS513细胞的生长有中等抑制作用(IC50: 20 ~ 100 μg/ml)。DCM-和H2O提取物对HT-29细胞生长有明显抑制作用。较高浓度(100 μg/ml)的己烷-和DCM-提取物能轻微刺激Caco-2细胞的生长。各提取物对结肠癌细胞的杀伤作用均大于对正常结肠细胞的杀伤作用。阿霉素与苜蓿提取物的联合研究显示出协同生长抑制作用(CI < 1)。与维拉帕米相比，HCT-15和LS513细胞对阿霉素的敏感性分别提高2.08 ~ 74.07倍和2.21 ~ 300.7倍，维拉帕米分别提高1.41倍和0.05倍。sativa L.提取物对结肠细胞具有直接的选择性细胞毒作用，具有逆转阿霉素耐药性的潜力。

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Synergy Medicine-Medicine (miscellaneous)

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