Induction of p53-Dependent G1 Cell Cycle Arrest by <i>Rhus verniciflua</i> Stokes Extract in
Human Breast Carcinoma MCF-7 Cells

Hong, Sang-hoon; Han, Min-ho; Choi, Yung-hyun; Park, Sang-eun

The Journal of Internal Korean Medicine > Volume 36(1); 2015 > Article

Article

The Journal of Internal Korean Medicine 2015;36(1): 13-21.

MCF-7 인체 유방암 세포에서 옻나무 추출물이 p53-Dependent G1 Cell Cycle에 미치는 영향

홍상훈¹, 한민호², 최영현², 박상은¹

¹동의대학교 한의과대학 한방내과
²동의대학교 한의과대학 생화학교실

Induction of p53-Dependent G1 Cell Cycle Arrest by Rhus verniciflua Stokes Extract in Human Breast Carcinoma MCF-7 Cells

Sang-hoon Hong¹, Min-ho Han², Yung-hyun Choi², Sang-eun Park¹

¹Dept. of Korean Internal Medicine, College of Korean Medicine, Dong-Eui University
²Dept. of Biochemistry, College of Korean Medicine, Dong-Eui University

Correspondence

Sang-eun Park ,Tel: 052-226-8105, Email: pse@deu.ac.kr

Received: February 23, 2015, Accepted: March 23, 2015, Published online: March 30, 2015.

ABSTRACT

Objectives:
In Korea, Rhus verniciflua Stokes (RVS) has been used in traditional medicine for various diseases such as back pain, syndromes of the blood system in women, gastrointestinal disease, and cancer. However, the molecular mechanisms of its anti-cancer activity have not been clearly elucidated yet.

Methods:
This study investigated the possible mechanisms by which RVS extract (RVE) exerts its anti-proliferative action in cultured human breast carcinoma MCF-7 cells.

Results:
Treatment with RVE in MCF-7 cells resulted in inhibition of cell viability through G1 arrest of the cell cycle and induction of apoptosis in a time- and concentration-dependent manner, as determined by MTT assay and flow cytometry analysis. The induction of G1 arrest by RVE treatment was associated with the inhibition of cyclin D1, cyclin-dependent kinase (Cdk) 2, retinoblastoma protein (pRB), and mouse double minute 2 (MDM2) expression. Moreover, RVE treatment concentration dependently increased the levels of tumor suppressor p53, which was associated with the marked induction of Cdk inhibitors such as p21 (Waf1/Cip1) and p27 (Kip1). However, the inhibition of p53 function by the wild-type p53-specific inhibitor, pifithrin-α, abolished the above-mentioned effects of RVE, showing that p53 was responsible for the cytotoxicity of RVE.

Conclusions:
These data indicate that a molecular pathway involving p53-dependent G1 cell cycle arrest plays a pivotal role in the cellular response to RVE, and demonstrate the potential applications of RVE as an anti-cancer drug for breast cancer treatment.

Key words: Rhus verniciflua, breast cancer, G1 arrest, p53