Genipin Enhances the Therapeutic Effects of Oxaliplatin by Upregulating BIM in Colorectal Cancer

Bo Ram Kim, Yoon A. Jeong, Min Jee Jo, Seong Hye Park, Yoo Jin Na, Jung Lim Kim, Soyeon Jeong, Hye Kyeong Yun, Sanghee Kang, Dae Hee Lee, Sang Cheul Oh

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Despite an increase in the survival rate of patients with cancer 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 antitumor effects in vitro and in vivo in colorectal cancer 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. In addition, 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 colorectal cancer. The combination of oxaliplatin and genipin hold significant therapeutic potential with minimal adverse effects.

Original languageEnglish
Pages (from-to)751-761
Number of pages11
JournalMolecular cancer therapeutics
Volume18
Issue number4
DOIs
Publication statusPublished - 2019 Apr 1

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Kim, B. R., Jeong, Y. A., Jo, M. J., Park, S. H., Na, Y. J., Kim, J. L., Jeong, S., Yun, H. K., Kang, S., Lee, D. H., & Oh, S. C. (2019). Genipin Enhances the Therapeutic Effects of Oxaliplatin by Upregulating BIM in Colorectal Cancer. Molecular cancer therapeutics, 18(4), 751-761. https://doi.org/10.1158/1535-7163.MCT-18-0196