Introduction: Doxorubicin is a chemotherapeutic agent that is used in the treatment of cancers, but its clinical application is limited due to serious side effects such as cardiotoxicity. Methanolic extract of Crocus pallasii subsp. haussknechtii corms exhibits cytotoxicity effects on MDA-MB-231 human breast cancer cell line at the concentrations higher than 100 µg/mL. In this study, cytotoxic effects of doxorubicin alone and in combination with methanolic extract of Crocus pallasii subsp. haussknechtii corms on MDA-MB-231 tumor cell line were investigated. Methods: Stock solution of methanolic extract was prepared in dimethyl sulfoxide (DMSO), and serial dilutions were prepared in phosphate-buffered saline (PBS). The final concentration of DMSO in all experiments was 1%. Different concentrations of doxorubicin and corms extract were added to the cultured cells and incubated for 48 h. Cell survival was evaluated using the cell viability MTT test. All data were analyzed by SPSS software version 20.0 and mean comparison of data was performed based on Duncan test at P < 0.05 level. Results: The results indicated that the methanolic extract of Crocus pallasii subsp. haussknechtii corms at the concentrations less than 100 µg/mL did not reduce cell viability and has a growth inhibitory effect at the higher concentrations. Doxorubicin alone at all the tested concentrations (0.46, 0.92, 4.6, and 9.2 nM) induced cell growth inhibition in MDA-MB-231 cells, with IC50 values of 3.05±0.04 nM at 48 h. Co-treatment of doxorubicin and the corms extract at 25 and 50 µg/mL concentrations reduced the percentage of cell viability in a dose-dependent manner. The IC50 value of doxorubicin in the presence of the corms extract against MDA-MB-231 cancer cells was less than 0.46 nM at 48 h. Conclusion: Methanolic extract of Crocus pallasii subsp. haussknechtii corms potentiates doxorubicin cytotoxicity against MDA-MB-231 breast cancer cells. Thus, co-administration of doxorubicin and the corms extract of Crocus pallasii subsp. haussknechtii as a medicinal plant may be a useful strategy for enhancing the chemotherapeutic effects of doxorubicin at lower concentrations.
