SH003 selectively induces p73‑dependent apoptosis in triple‑negative breast cancer cells

Choi,Eun Kyoung; Kim,Seung‑Mi; Hong,Seung‑Woo; Moon,Jai‑Hee; Shin,Jae‑Sik; Kim,Jeong Hee; Hwang,Ih‑Yeon; Jung,Soo‑A; Lee,Dae‑Hee; Lee,Eun Young; Lee,Seul; Kim,Hyunwoo; Kim,Daejin; Kim,Yeong Seok; Choi,Youn Kyung; Kim,Hyo In; Choi,Hyeong Sim; Cho,Sung‑Gook; Kim,Jeong Eun; Kim,Kyu Pyo; Hong,Yong Sang; Lee,Won Keun; Lee,Jung Shin; Kim,Tae Won; Ko,Seong‑Gyu; Jin,Dong‑Hoon

doi:10.3892/mmr.2016.5722

SH003 selectively induces p73‑dependent apoptosis in triple‑negative breast cancer cells

Authors:
- Eun Kyoung Choi
- Seung‑Mi Kim
- Seung‑Woo Hong
- Jai‑Hee Moon
- Jae‑Sik Shin
- Jeong Hee Kim
- Ih‑Yeon Hwang
- Soo‑A Jung
- Dae‑Hee Lee
- Eun Young Lee
- Seul Lee
- Hyunwoo Kim
- Daejin Kim
- Yeong Seok Kim
- Youn Kyung Choi
- Hyo In Kim
- Hyeong Sim Choi
- Sung‑Gook Cho
- Jeong Eun Kim
- Kyu Pyo Kim
- Yong Sang Hong
- Won Keun Lee
- Jung Shin Lee
- Tae Won Kim
- Seong‑Gyu Ko
- Dong‑Hoon Jin
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Affiliations: Innovative Cancer Research, ASAN Institute for Life Science, Asan Medical Center, Seoul 138‑736, Republic of Korea, Department of Anatomy and Research Center for Tumor Immunology, Inje University College of Medicine, Pusan 614‑735, Republic of Korea, Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University, Seoul 130‑701, Republic of Korea, Division of Biosciences and Bioinformatics, Myongji University, Youngin, Kyunggi‑Do 449‑728, Republic of Korea
Published online on: September 6, 2016 https://doi.org/10.3892/mmr.2016.5722
Pages: 3955-3960

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Abstract

Triple-negative breast cancer (TNBC) is a breast cancer subtype that has an aggressive phenotype, is highly metastatic, has limited treatment options and is associated with a poor prognosis. In addition, metastatic TNBC has no preferred standard chemotherapy due to resistance to anthracyclines and taxanes. The present study demonstrated that a herbal extract, SH003, reduced cell viability and induced apoptosis in TNBC without cell cytotoxicity. Cell viability was examined using trypan blue exclusion and colony formation assays, which revealed a decrease in the cell viability. Additionally, apoptosis was determined using flow cytometry and a sub‑G1 assay, which revealed an increase in the proportion of cells in the sub‑G1 phase. The present study investigated the anticancer effect of SH003 in the Hs578T, MDA‑MB‑231 and ZR‑751 TNBC cell lines, and in the MCF7 and T47D non‑TNBC cell lines. Western blot analysis revealed that the expression levels of poly‑ADP‑ribose polymerase (PARP) cleavage protein in cells treated with SH003 were increased dose‑dependent manner, indicating that SH003 induced apoptosis via a caspase‑dependent pathway. Pre‑treatment with the caspase inhibitor Z‑VAD reduced SH003‑induced apoptosis was examined using trypan blue exclusion. Moreover, SH003 treatment enhanced the p73 levels in MDA‑MB‑231 cells but not in MCF7 cells. Transfection of p73 small interfering RNA (siRNA) in MDA‑MB0231 cells revealed that the apoptotic cell death induced by SH003 was significantly impaired in comparison with scramble siRNA transfected MDA‑MB‑231 cells. This was examined using trypan blue exclusion and flow cytometry analysis (sub‑G1). In addition, SH003 and paclitaxel exhibited synergistic anticancer effects on TNBC cells. The results indicate that SH003 exerts its anticancer effect via p73 protein induction and exhibits synergistic anticancer effects when combined with paclitaxel.

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