z-logo
open-access-imgOpen Access
SH003 selectively induces p73-dependent apoptosis in triple-negative breast cancer cells
Author(s) -
Eun Kyoung Choi,
SeungMi Kim,
SeungWoo Hong,
JaiHee Moon,
JaeSik Shin,
Jeong Hee Kim,
In-Sun Hwang,
Sun Young Jung,
DaeHee Lee,
Eun Young Lee,
Seul Lee,
Hyun Woo Kim,
Daejin Kim,
Yeong Seok Kim,
Youn Kyung Choi,
Hyo In Kim,
Ha Na Choi,
SungGook Cho,
Kyu Pyo Kim,
Yong Sang Hong,
Won Keun Lee,
Jung Shin Lee,
Tae Won Kim,
SeongGyu Ko,
Dayong Jin
Publication year - 2016
Publication title -
molecular medicine reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.727
H-Index - 56
eISSN - 1791-3004
pISSN - 1791-2997
DOI - 10.3892/mmr.2016.5722
Subject(s) - trypan blue , apoptosis , viability assay , cell cycle , cancer research , flow cytometry , biology , transfection , triple negative breast cancer , microbiology and biotechnology , cell , cell culture , cancer , breast cancer , biochemistry , genetics
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.

The content you want is available to Zendy users.

Already have an account? Click here to sign in.
Having issues? You can contact us here