Biomol Ther.  2018 May;26(3):322-327. 10.4062/biomolther.2017.235.

Gomisin G Inhibits the Growth of Triple-Negative Breast Cancer Cells by Suppressing AKT Phosphorylation and Decreasing Cyclin D1

• Maharjan S
• Park BK
• Lee SI
• Lim Y
• Lee K
• Kwon HJ

• KMID: 2421742
• DOI: http://doi.org/10.4062/biomolther.2017.235

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.

Keyword

AKT; Cell cycle; Cell proliferation; Cyclin D1; Gomisin G; Triple negative breast cancer

MeSH Terms

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*
Cyclin D1
Cyclins
Estrogens
Receptor, Epidermal Growth Factor
Receptors, Progesterone