US EPA

8197920 

Journal Article 

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

Mangoato, IM; Mahadevappa, CP; Matsabisa, MG 

2019 

Elsevier GmbH 

9 

English 

10.1016/j.synres.2019.100056 

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. © 2019 Elsevier GmbH 

Cannabis; Colon cancer; Cytotoxicity; Doxorubicin; MDR; Verapamil