SH003 selectively induces p73‑dependent apoptosis in triple‑negative breast cancer cells.
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.
Innovative Cancer Research, ASAN Institute for Life Science, Asan Medical Center, Seoul 138‑736, Republic of Korea.
Eun Kyoung
EK
Choi
Innovative Cancer Research, ASAN Institute for Life Science, Asan Medical Center, Seoul 138‑736, Republic of Korea.
Seung-Mi
SM
Kim
Innovative Cancer Research, ASAN Institute for Life Science, Asan Medical Center, Seoul 138‑736, Republic of Korea.
Seung-Woo
SW
Hong
Innovative Cancer Research, ASAN Institute for Life Science, Asan Medical Center, Seoul 138‑736, Republic of Korea.
Jai-Hee
JH
Moon
Innovative Cancer Research, ASAN Institute for Life Science, Asan Medical Center, Seoul 138‑736, Republic of Korea.
Jae-Sik
JS
Shin
Innovative Cancer Research, ASAN Institute for Life Science, Asan Medical Center, Seoul 138‑736, Republic of Korea.
Jeong Hee
JH
Kim
Innovative Cancer Research, ASAN Institute for Life Science, Asan Medical Center, Seoul 138‑736, Republic of Korea.
Ih-Yeon
IY
Hwang
Innovative Cancer Research, ASAN Institute for Life Science, Asan Medical Center, Seoul 138‑736, Republic of Korea.
Soo-A
SA
Jung
Innovative Cancer Research, ASAN Institute for Life Science, Asan Medical Center, Seoul 138‑736, Republic of Korea.
Dae-Hee
DH
Lee
Innovative Cancer Research, ASAN Institute for Life Science, Asan Medical Center, Seoul 138‑736, Republic of Korea.
Eun Young
EY
Lee
Innovative Cancer Research, ASAN Institute for Life Science, Asan Medical Center, Seoul 138‑736, Republic of Korea.
Seul
S
Lee
Innovative Cancer Research, ASAN Institute for Life Science, Asan Medical Center, Seoul 138‑736, Republic of Korea.
Hyunwoo
H
Kim
Department of Anatomy and Research Center for Tumor Immunology, Inje University College of Medicine, Pusan 614‑735, Republic of Korea.
Daejin
D
Kim
Department of Anatomy and Research Center for Tumor Immunology, Inje University College of Medicine, Pusan 614‑735, Republic of Korea.
Yeong Seok
YS
Kim
Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University, Seoul 130‑701, Republic of Korea.
Youn Kyung
YK
Choi
Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University, Seoul 130‑701, Republic of Korea.
Hyo In
HI
Kim
Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University, Seoul 130‑701, Republic of Korea.
Hyeong Sim
HS
Choi
Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University, Seoul 130‑701, Republic of Korea.
Sung-Gook
SG
Cho
Innovative Cancer Research, ASAN Institute for Life Science, Asan Medical Center, Seoul 138‑736, Republic of Korea.
Jeong Eun
JE
Kim
Innovative Cancer Research, ASAN Institute for Life Science, Asan Medical Center, Seoul 138‑736, Republic of Korea.
Kyu Pyo
KP
Kim
Innovative Cancer Research, ASAN Institute for Life Science, Asan Medical Center, Seoul 138‑736, Republic of Korea.
Yong Sang
YS
Hong
Division of Biosciences and Bioinformatics, Myongji University, Youngin, Kyunggi‑Do 449‑728, Republic of Korea.
Won Keun
WK
Lee
Innovative Cancer Research, ASAN Institute for Life Science, Asan Medical Center, Seoul 138‑736, Republic of Korea.
Jung Shin
JS
Lee
Innovative Cancer Research, ASAN Institute for Life Science, Asan Medical Center, Seoul 138‑736, Republic of Korea.
Tae Won
TW
Kim
Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University, Seoul 130‑701, Republic of Korea.
Seong-Gyu
SG
Ko
Innovative Cancer Research, ASAN Institute for Life Science, Asan Medical Center, Seoul 138‑736, Republic of Korea.
Dong-Hoon
DH
Jin
D029969:Angelica; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D027883:Astragalus Plant; D001940:Breast / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005260:Female; D006801:Humans; D017239:Paclitaxel / Q000494:pharmacology; D010936:Plant Extracts / Q000494:pharmacology*; D029778:Trichosanthes; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000072160:Tumor Protein p73 / Q000378:metabolism*
D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts; C000613735:SH003 extract; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D020169:Caspases; D017239:Paclitaxel