Genipin enhances the therapeutic effects of oxaliplatin by upregulating BIM in colorectal cancer.
Mol Cancer Ther. 2019 Feb 20. Epub 2019 Feb 20. PMID: 30787174
Bo Ram Kim
Despite an increase in the survival rate of cancer patients owing to the use of current chemotherapeutic agents, adverse effects of cancer therapies remain a concern. Combination therapies have been developed to increase efficacy, reduce adverse effects, and overcome drug resistance. Genipin is a natural product derived from Gardenia jasminoides, which has been associated with anti-inflammatory, anti-angiogenic, and anti-proliferative effects; hypertension; and anti-ischemic brain injuries. However, the enhancement of oxaliplatin sensitivity by genipin remains unexplored. Our study showed that a combination of genipin and oxaliplatin exerts synergistic anti-tumor effects in vitro and in vivo in colorectal cancer (CRC) cell lines through the reactive oxygen species (ROS)/endoplasmic reticulum (ER) stress/BIM pathway. Importantly, the combination did not affect normal colon cells. BIM knockdown markedly inhibited apoptosis induced by the combination. Additionally, genipin induced ROS by inhibiting superoxide dismutase 3 activity. These findings suggest that genipin may be a novel agent for increasing the sensitivity of oxaliplatin against CRC. The combination of oxaliplatin and genipin hold significant therapeutic potential with minimal adverse effects.