Falcarindiol and dichloromethane fraction are bioactive components in Oplopanax elatus: Colorectal cancer chemoprevention via induction of apoptosis and G2/M cell cycle arrest mediated by cyclin A upregulation (2024)

J Appl Biomed 19:113-124, 2021|DOI:10.32725/jab.2021.013

Falcarindiol and dichloromethane fraction are bioactive components in Oplopanax elatus: Colorectal cancer chemoprevention via induction of apoptosis and G2/M cell cycle arrest mediated by cyclin A upregulation

Chong-Zhi Wang^{1, 2}, Yun Luo^{1, 2}, Wei-Hua Huang², Jinxiang Zeng², Chun-Feng Zhang², Mallory Lager², Wei Du³, Ming Xu⁴, Chun-Su Yuan^{2, 4, *}

¹Ministry of Education, Jiangxi University of Traditional Chinese Medicine, Key Laboratory of Modern Preparation of Traditional Chinese Medicine, Nanchang, P.R. China

²University of Chicago, Tang Center for Herbal Medicine Research, and Department of Anesthesia and Critical Care, Chicago, Illinois, USA

³University of Chicago, Ben May Department for Cancer Research, Chicago, Illinois, USA

⁴University of Chicago, Committee on Clinical Pharmacology and Pharmacogenomics, Chicago, Illinois, USA

Oplopanax elatus (Nakai) Nakai has a long history of use as an ethnomedicine by the people living in eastern Asia. However, its bioactive constituents and cancer chemopreventive mechanisms are largely unknown. The aim of this study was to prepare O. elatus extracts, fractions, and single compounds and to investigate the herb's antiproliferative effects on colon cancer cells and the involved mechanisms of action. Two polyyne compounds were isolated from O. elatus, falcarindiol and oplopandiol. Based on our HPLC analysis, falcarindiol and oplopandiol are major constituents in the dichloromethane (CH2Cl2) fraction. For the HCT-116 cell line, the dichloromethane fraction showed significant effects. Furthermore, the IC50 for falcarindiol and oplopandiol was 1.7 µM and 15.5 µM, respectively. In the mechanistic study, after treatment with 5 µg/ml for 48 h, dichloromethane fraction induced cancer cell apoptosis by 36.5% (p < 0.01% vs. control of 3.9%). Under the same treatment condition, dichloromethane fraction caused cell cycle arrest at the G2/M phase by 32.6% (p < 0.01% vs. control of 23.4%), supported by upregulation of key cell cycle regulator cyclin A to 21.6% (p < 0.01% vs. control of 8.6%). Similar trends were observed by using cell line HT-29. Data from this study filled the gap between phytochemical components and the cancer chemoprevention of O. elatus. The dichloromethane fraction is a bioactive fraction, and falcarindiol is identified as an active constituent. The mechanisms involved in cancer chemoprevention by O. elatus were apoptosis induction and G2/M cell cycle arrest mediated by a key cell cycle regulator cyclin A.

Keywords: Apoptosis; Cell cycle; Colorectal cancer; Cyclin A; Dichloromethane fraction; Falcarindiol; Oplopanax elatus

Grants and funding:

This work was supported in part by NIH/NCCAM grants P01 AT004418 and K01 AT005362, the grants of the National Natural Science Foundation of China (81760711), and the State Scholarship Fund of China Scholarship Council (201808360056).

Conflicts of interest:

The authors declare that they have no conflict of interests.

Received: October 15, 2020; Revised: April 6, 2021; Accepted: May 3, 2021; Prepublished online: May 5, 2021; Published: May 10, 2021 Show citation

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