Anticancer Effect of the Ethyl Acetate Fraction from Orostachys japonicus on MDA-MB-231 Human Breast Cancer Cells through Extensive Induction of Apoptosis, Cell Cycle Arrest, and Antimetastasis.

Ji-Hye Kwon,Deok-Seon Ryu,Hyun-Ji Lee,Jae-Hyeon Kim,Dong-Seok Lee

doi:10.1155/2019/8951510

Abstract

The antibreast cancer activities of the ethyl acetate fraction from Orostachys japonicus (OJEF) were investigated in MDA-MB-231 human breast cancer cells through WST assay, DAPI staining, flow cytometry analysis, and western blotting. OJEF effectively inhibited MDA-MB-231 cells by inducing apoptosis via intrinsic, extrinsic, and endoplasmic reticulum (ER) stress response pathways, cell cycle arrest at the G1/S phase, and antimetastasis including inhibition of tight junction, adherens junction, invasion, and migration. The MAPK family-mediated upstream signal transduction through p-p38 and p-ERK was considered to affect the downstream signal transduction including induction of apoptosis, cell cycle arrest, and antimetastasis. In conclusion, we executed an integrated study on the anticancer activities of OJEF, which extensively induced apoptosis, cell cycle arrest, and antimetastasis in estrogen-independent MDA-MB-231 human breast cancer cells known to be liable to metastasize.

Highlights

According to the latest data, cancer is the leading cause of mortality in Korea
We explored the inhibitory activity of the ethyl acetate fraction from O. japonicus (OJEF) in MDA-MB-231 human breast cancer cells; we examined antimetastasis as well as apoptosis and cell cycle arrest; this study is further advanced and differentiated from previous studies. erefore, the purpose of this work was to systematically establish the anticancer activities of OJEF in estrogen-independent MDA-MB-231 cells known to be prone to metastasize by investigating the molecular mechanisms on overall induction of apoptosis, cell cycle arrest, and antimetastasis including inhibition of tight junction, adherens junction, invasion, and migration
Staining with DAPI showed condensed chromatin, fragmented nuclei, and apoptotic bodies in OJEF-treated cells. e percentage of apoptotic bodies increased in a dose-dependent manner (Figure 2(a)). ese morphological changes represent that OJEF induces apoptosis in MDA-MB-231 cells [7]

Summary

Introduction

According to the latest data, cancer is the leading cause of mortality in Korea. Among all cancers, breast cancer is the second main cause of cancer-related death in women worldwide today [1]. Most current chemotherapies are combinations of chemical substances with low or no selectivity towards cancer cells, and they are usually toxic to both cancer and normal cells. Many studies have been conducted to find new anticancer drugs that are only effective to cancer cells to avoid causing harm to patients. Abnormal apoptosis is known to cause cancer and degenerative diseases. Erefore, recovering normal apoptosis in cancer cells has been considered a key indicator of the anticancer activity of potential remedy substances [7]. Since cancer cells continue to proliferate uncontrollably without maintaining normal proliferation, the cell cycle arrest is another definite indicator of anticancer activity. Cell division is divided into the G1 phase, the synthetic S phase, the G2 phase, and the M

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