J Cancer 2020; 11(2):460-467. doi:10.7150/jca.34773 This issue

Research Paper

Genipin increases oxaliplatin-induced cell death through autophagy in gastric cancer

Bo Ram Kim1*, Yoon A Jeong2, Dae Young Kim2, Jung Lim Kim1, Soyeon Jeong1, Yoo Jin Na2, Hye Kyeong Yun2, Seong Hye Park1, Min Jee Jo2, Hassan Ashktorab3, Duane T Smoot4, Dae-Hee Lee1, Sang Cheul Oh1✉

1. Department of Oncology, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Republic of Korea.
2. Graduate School of Medicine, Korea University College of Medicine, Seoul, Republic of Korea.
3. Department of Medicine, Howard University, Washington, District of Columbia, 20060, USA.
4. Department of Medicine, Meharry Medical Center, Nashville, TN, 37208, USA.
*first author

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Citation:
Kim BR, Jeong YA, Kim DY, Kim JL, Jeong S, Na YJ, Yun HK, Park SH, Jo MJ, Ashktorab H, Smoot DT, Lee DH, Oh SC. Genipin increases oxaliplatin-induced cell death through autophagy in gastric cancer. J Cancer 2020; 11(2):460-467. doi:10.7150/jca.34773. Available from https://www.jcancer.org/v11p0460.htm

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Abstract

Oxaliplatin is used for treatment in combination with many drugs. However, the survival rate is still low due to side effects and drug resistance. Therefore, the combination with natural products was required for increasing efficacy and reducing side effects.

Genipin, a natural product derived from the Gardenia jasminoides, associated with anti-angiogenic, anti-proliferative, hypertension, inflammatory, and the Hedgehog pathway. It is not known that genipin increases the therapeutic effect of oxaliplatin in gastric cancer. In this study, we found that genipin sensitizes oxaliplatin-induced apoptosis for the first time using colony forming assay, FACS analysis, and western blotting in gastric cancer. Additionally, genipin induced p53 expression in AGS, MKN45, and MKN28 cells. Also, genipin induced autophagy and LC3 expression. Knockdown of LC3 decreased cell death enhanced by the combination of oxaliplatin and genipin. In summary, we showed that genipin increases the oxaliplatin-induced cell death via p53-DRAM autophagy. Based on this, we suggest that genipin is a sensitizer of oxaliplatin.

Keywords: Oxaliplatin, Genipin, p53, Autophagy.