Effects of kefir on doxorubicin-induced multidrug resistance in human colorectal cancer cells
Do Hyun Kim, Chang Hee Jeong, Wei Cheng, Hyuk-Cheol Kwon, Dong‐Hyeon Kim, Kun‐Ho Seo, Youngsok Choi, Sung Gu Han
Abstract
Kefir, an acidic-alcoholic fermented milk product, is known to be associated with reduced cancer incidence. Multidrug resistance (MDR) against chemotherapeutic agents frequently occurs in cancer cells, leading to cancer therapy failure. To explore the potential chemo-sensitizing effects of kefir (i.e., kefir supernatant), drug-resistant human colorectal cancer cells (HT-29) were produced by exposing cells to 34 nm of doxorubicin (DOX) for 12 weeks. Results demonstrated that cells treated with kefir attenuated MDR and improved the anticancer effect of DOX in drug-resistant cells. Kefir increased intracellular accumulation of ROS and DOX in drug-resistant cells. Kefir decreased the gene and protein expressions of adenosine tri-phosphate binding cassette (ABC) transporters, a drug efflux pump, in drug-resistant cells. Upstream regulators of ABC transporters, such as ERK 1/2, JNK and NF-κB were also modulated by kefir. Our data suggest that kefir consumption may be helpful in patients receiving DOX chemotherapy owing to its chemo-sensitizing effects.