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

5 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

Fingerprint

oxaliplatin
Endoplasmic Reticulum Stress
apoptosis
Colorectal Neoplasms
cancer
Down-Regulation
Cells
Apoptosis
Tumors
Neoplasms
tumor
drug
Oncology
Cytotoxins
Vegetables
Cell death
Fruits
Heterografts
Alkylating Agents
Pharmaceutical Preparations

Keywords

  • ABCG2
  • ER stress signaling
  • Lupeol
  • Oxaliplatin resistance

ASJC Scopus subject areas

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

Cite this

Lupeol alters ER stress-signaling pathway by downregulating ABCG2 expression to induce Oxaliplatin-resistant LoVo colorectal cancer cell apoptosis. / Chen, Ming Cheng; Hsu, Hsi Hsien; Chu, Yuan Yuan; Cheng, Sue Fei; Shen, Chia Yao; Lin, Yi Jiun; Chen, Ray Jade; Viswanadha, Vijaya Padma; Lin, Yueh Min; Huang, Chih Yang.

In: Environmental Toxicology, 01.01.2018.

Research output: Contribution to journalArticle

Chen, Ming Cheng ; Hsu, Hsi Hsien ; Chu, Yuan Yuan ; Cheng, Sue Fei ; Shen, Chia Yao ; Lin, Yi Jiun ; Chen, Ray Jade ; Viswanadha, Vijaya Padma ; Lin, Yueh Min ; Huang, Chih Yang. / Lupeol alters ER stress-signaling pathway by downregulating ABCG2 expression to induce Oxaliplatin-resistant LoVo colorectal cancer cell apoptosis. In: Environmental Toxicology. 2018.
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AU - Chen, Ming Cheng

AU - Hsu, Hsi Hsien

AU - Chu, Yuan Yuan

AU - Cheng, Sue Fei

AU - Shen, Chia Yao

AU - Lin, Yi Jiun

AU - Chen, Ray Jade

AU - Viswanadha, Vijaya Padma

AU - Lin, Yueh Min

AU - Huang, Chih Yang

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AB - 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.

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