Hyesu Jeon1, Diem Thi Ngoc Huynh2, Naehwan Baek1, Thuy Le Lam Nguyen1, Kyung-Sun Heo3. 1. College of Pharmacy and Institute of Drug Research and Development, Chungnam National University, 99, Daehak-ro, Yuseong-Gu, Daejeon, South Korea. 2. College of Pharmacy and Institute of Drug Research and Development, Chungnam National University, 99, Daehak-ro, Yuseong-Gu, Daejeon, South Korea; Department of Pharmacy, Da Nang University of Medical Technology and Pharmacy, Da Nang, Vietnam. 3. College of Pharmacy and Institute of Drug Research and Development, Chungnam National University, 99, Daehak-ro, Yuseong-Gu, Daejeon, South Korea. Electronic address: kheo@cnu.ac.kr.
Abstract
BACKGROUND: Ginsenoside-Rg2 (G-Rg2) is a protopanaxatriol-type ginsenoside isolated from ginseng. It has been found to exhibit various pharmacological effects, including antioxidant, anti-inflammatory, and anticancer effects. PURPOSE: This study aimed to investigate the anticancer effects of G-Rg2 on estrogen receptor-positive MCF-7 breast cancer (BC) cells, and the underlying mechanisms involving in reactive oxygen species (ROS) production. STUDY DESIGN/ METHODS: Cell viability, cell cycle distribution, apoptosis, and ROS production were measured following exposure to G-Rg2. The protein expression levels of p-ERK1/2, p-Akt, PARP, p-Rb, cyclin D1, CDK6, and p-AMPK were quantified using western blot analysis. The in vivo activity of G-Rg2 was assessed in a xenograft model. Immunohistochemistry staining for p-Rb and p-AMPK was performed in tumor tissues. RESULTS: G-Rg2 significantly decreased cell viability but increased cell apoptosis. In MCF-7 cells, G-Rg2 increased ROS production by inhibiting ERK1/2 and Akt activation. G-Rg2-induced ROS induced G0/G1 cell cycle arrest and AMPK phosphorylation. In the xenograft model, the 5 mg/kg G-Rg2-treated group showed decreased tumor volume and weight, similar to the 5 mg/kg 4-OHT-treated group, compared to the control group. Immunohistochemistry staining showed that G-Rg2 treatment decreased Rb phosphorylation, while increasing AMPK phosphorylation in tumor tissues. CONCLUSION: G-Rg2 has potential anticancer effects by increasing the ROS-AMPK signaling pathway and inhibiting ERK1/2 and Akt activation-mediated cell proliferation and cell cycle progression in MCF-7 BC cells.
BACKGROUND:Ginsenoside-Rg2 (G-Rg2) is a protopanaxatriol-type ginsenoside isolated from ginseng. It has been found to exhibit various pharmacological effects, including antioxidant, anti-inflammatory, and anticancer effects. PURPOSE: This study aimed to investigate the anticancer effects of G-Rg2 on estrogen receptor-positive MCF-7breast cancer (BC) cells, and the underlying mechanisms involving in reactive oxygen species (ROS) production. STUDY DESIGN/ METHODS: Cell viability, cell cycle distribution, apoptosis, and ROS production were measured following exposure to G-Rg2. The protein expression levels of p-ERK1/2, p-Akt, PARP, p-Rb, cyclin D1, CDK6, and p-AMPK were quantified using western blot analysis. The in vivo activity of G-Rg2 was assessed in a xenograft model. Immunohistochemistry staining for p-Rb and p-AMPK was performed in tumor tissues. RESULTS:G-Rg2 significantly decreased cell viability but increased cell apoptosis. In MCF-7 cells, G-Rg2 increased ROS production by inhibiting ERK1/2 and Akt activation. G-Rg2-induced ROS induced G0/G1 cell cycle arrest and AMPK phosphorylation. In the xenograft model, the 5 mg/kg G-Rg2-treated group showed decreased tumor volume and weight, similar to the 5 mg/kg 4-OHT-treated group, compared to the control group. Immunohistochemistry staining showed that G-Rg2 treatment decreased Rb phosphorylation, while increasing AMPK phosphorylation in tumor tissues. CONCLUSION:G-Rg2 has potential anticancer effects by increasing the ROS-AMPK signaling pathway and inhibiting ERK1/2 and Akt activation-mediated cell proliferation and cell cycle progression in MCF-7 BC cells.