Gomisin G Inhibits the Growth of Triple-Negative Breast Cancer Cells by Suppressing AKT Phosphorylation and Decreasing Cyclin D1.
10.4062/biomolther.2017.235
- Author:
Sony MAHARJAN
1
;
Byoung Kwon PARK
;
Su In LEE
;
Yoonho LIM
;
Keunwook LEE
;
Hyung Joo KWON
Author Information
1. Center for Medical Science Research, College of Medicine, Hallym University, Chuncheon 24252, Republic of Korea. hjookwon@hallym.ac.kr
- Publication Type:Original Article
- Keywords:
AKT;
Cell cycle;
Cell proliferation;
Cyclin D1;
Gomisin G;
Triple negative breast cancer
- MeSH:
Apoptosis;
Breast Neoplasms;
Cell Cycle;
Cell Cycle Checkpoints;
Cell Line;
Cell Proliferation;
Cyclin D1*;
Cyclins*;
Estrogens;
G1 Phase;
Humans;
Phosphorylation*;
Prognosis;
Receptor, Epidermal Growth Factor;
Receptors, Progesterone;
Retinoblastoma;
Signal Transduction;
Survival Rate;
Triple Negative Breast Neoplasms*
- From:Biomolecules & Therapeutics
2018;26(3):322-327
- CountryRepublic of Korea
- Language:English
-
Abstract:
A type of breast cancer with a defect in three molecular markers such as the estrogen receptor, progesterone receptor, and human epidermal growth factor receptor is called triple-negative breast cancer (TNBC). Many patients with TNBC have a lower survival rate than patients with other types due to a poor prognosis. In this study, we confirmed the anti-cancer effect of a natural compound, Gomisin G, in TNBC cancer cells. Treatment with Gomisin G suppressed the viability of two TNBC cell lines, MDA-MB-231 and MDA-MB-468 but not non-TNBC cell lines such as MCF-7, T47D, and ZR75-1. To investigate the molecular mechanism of this activity, we examined the signal transduction pathways after treatment with Gomisin G in MDA-MB-231 cells. Gomisin G did not induce apoptosis but drastically inhibited AKT phosphorylation and reduced the amount of retinoblastoma tumor suppressor protein (Rb) and phosphorylated Rb. Gomisin G induced in a proteasome-dependent manner a decrease in Cyclin D1. Consequently, Gomisin G causes cell cycle arrest in the G1 phase. In contrast, there was no significant change in T47D cells except for a mild decrease in AKT phosphorylation. These results show that Gomisin G has an anti-cancer activity by suppressing proliferation rather than inducing apoptosis in TNBC cells. Our study suggests that Gomisin G could be used as a therapeutic agent in the treatment of TNBC patients.
