Lupeol alters ER stress-signaling pathway by downregulating ABCG2 expression to induce Oxaliplatin-resistant LoVo colorectal cancer cell apoptosis

Ming Cheng Chen, Hsi Hsien Hsu, Yuan Yuan Chu, Sue Fei Cheng, Chia Yao Shen, Yi Jiun Lin, Ray Jade Chen, Vijaya Padma Viswanadha, Yueh Min Lin, Chih Yang Huang

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Colorectal cancer (CRC) is one of the most common cancers and causes of cancer-related death. There are several first-line chemotherapeutic drugs used to treat CRC. Oxaliplatin (OXA) is an alkylating cytotoxic agent that is usually combined with other chemotherapeutic drugs to treat stage II and stage III CRC. However, cancer cells commonly acquire multidrug resistance (MDR), which is a major obstruction to cancer treatment. Recent studies have shown that natural components from traditional Chinese medicine or foods that have many biological functions may be new adjuvant therapies in clinical trials. We challenged LoVo CRC cell lines with OXA in a dose-dependent manner to create an OXA-resistant model. The expression of ABCG2 was significantly higher, and levels of endoplasmic reticulum (ER) stress markers were lower than those Parental cells. However, Lupeol, which is found in fruits and vegetables, has been shown to have bioactive properties, including anti-tumor properties that are relevant to many diseases. In our study, Lupeol downregulated cell viability and activated cell apoptosis. Moreover, Lupeol decreased the expression of ABCG2 and activated ER stress to induce OXA-resistant cell death. Importantly, the anti-tumor effect of Lupeol in OXA-resistant cells was higher than that of LoVo Parental cells. In addition, we also confirmed our results with a xenograft animal model, and the tumor size significantly decreased after Lupeol injections. Our findings show that Lupeol served as a strong chemoresistant sensitizer and could be a new adjuvant therapy method for chemoresistant patients.

Original languageEnglish
JournalEnvironmental Toxicology
DOIs
Publication statusAccepted/In press - Jan 1 2018

Keywords

  • ABCG2
  • ER stress signaling
  • Lupeol
  • Oxaliplatin resistance

ASJC Scopus subject areas

  • Toxicology
  • Management, Monitoring, Policy and Law
  • Health, Toxicology and Mutagenesis

Fingerprint Dive into the research topics of 'Lupeol alters ER stress-signaling pathway by downregulating ABCG2 expression to induce Oxaliplatin-resistant LoVo colorectal cancer cell apoptosis'. Together they form a unique fingerprint.

  • Cite this

    Chen, M. C., Hsu, H. H., Chu, Y. Y., Cheng, S. F., Shen, C. Y., Lin, Y. J., Chen, R. J., Viswanadha, V. P., Lin, Y. M., & Huang, C. Y. (Accepted/In press). Lupeol alters ER stress-signaling pathway by downregulating ABCG2 expression to induce Oxaliplatin-resistant LoVo colorectal cancer cell apoptosis. Environmental Toxicology. https://doi.org/10.1002/tox.22544