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Ginsenoside Rg3 inhibit hepatocellular carcinoma growth via intrinsic apoptotic pathway
Jian-Wen Jiang1, Xin-Mei Chen, Xin-Hua Chen
1The Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, The Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China.
Aim:
To investigate the anti-tumor function of ginsenoside Rg3 on hepatocellular carcinoma (HCC) in vitro and in vivo, and its mechanism.
Methods:
Hep1-6 and HepG2 cells were treated by Rg3 in different concentrations (0, 50, 100 and 200 μg/mL) in vitro. After incubation for 0, 6, 12, 24 and 48 h, cell viability was measured by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay. Apoptosis was identified by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling. Caspase-3 activity was measured by chromophore p-nitroanilide and flow cytometry. Bcl-2 family proteins were ascertained by Western-blotting. Mitochondria membrane potential was detected by 5, 5', 6' 6' - tetrachloro-1, 1', 3, 3' - tetraethylbenzimidazolylcarbocyanine iodide. Forty liver tumor-bearing C57Bl6 mice were divided randomly into 4 groups for intra-tumor injection of saline, ginsenoside Rg3, cyclophosphamide (CTX) and ginsenoside Rg3 + CTX combination.
Results:
The survival time was followed up to 102 d. The mice in the Rg3 + CTX group showed significant increased survival time compared with those in the control group (P < 0.05). Rg3 could inhibit HCC cell proliferation and induce cell apoptosis in vitro in the concentration and time dependent manner. It also induced mitochondria membrane potential to decrease. Caspase-3 activation can be blocked by the inhibitor z-DEVD-FMK. Bax was up-regulated while Bcl-2 and Bcl-XL were down-regulated after Rg3 treatment.
Conclusion:
Our data suggested that Rg3 alone or combined with CTX inhibited tumor growth in vivo and prolonged mouse survival time by inducing HCC cell apoptosis via intrinsic pathway by expression alterations of Bcl-2 family proteins.
Insights
Ginsenoside Rg3 shows anti-tumor effects against hepatocellular carcinoma (HCC) by inducing apoptosis. This natural compound, alone or with chemotherapy, prolongs survival in mice with liver tumors.
Area of Science:
- Pharmacology
- Oncology
- Biochemistry
Background:
- Hepatocellular carcinoma (HCC) is a major global health concern with limited effective treatments.
- Ginsenoside Rg3, a compound derived from ginseng, has shown potential anti-cancer properties.
- Understanding the mechanisms of Rg3's action is crucial for developing novel HCC therapies.
Purpose of the Study:
- To evaluate the anti-tumor efficacy of ginsenoside Rg3 against HCC.
- To elucidate the in vitro and in vivo mechanisms underlying Rg3's anti-cancer effects.
- To investigate the combined effect of Rg3 and cyclophosphamide (CTX) in HCC treatment.
Main Methods:
- In vitro studies involved treating Hep1-6 and HepG2 cells with varying concentrations of Rg3.
- Cell viability, apoptosis, caspase-3 activity, and mitochondrial membrane potential were assessed.
- In vivo studies utilized a mouse model of HCC, comparing Rg3, CTX, and combination therapy.
Main Results:
- Ginsenoside Rg3 inhibited HCC cell proliferation and induced apoptosis in a dose- and time-dependent manner.
- Rg3 treatment led to decreased mitochondrial membrane potential and altered Bcl-2 family protein expression (upregulated Bax, downregulated Bcl-2/Bcl-XL).
- Combination therapy with Rg3 and CTX significantly increased survival time in tumor-bearing mice.
Conclusions:
- Ginsenoside Rg3 exhibits significant anti-tumor activity against HCC.
- Rg3 induces apoptosis in HCC cells through the intrinsic pathway, involving Bcl-2 family protein modulation.
- Rg3, alone or in combination with CTX, offers a promising therapeutic strategy for HCC, enhancing survival rates.