Aqueous Ocimum gratissimum extract induces cell apoptosis in human hepatocellular carcinoma cells
Chen-Cheng Huang1,2, Jin-Ming Hwang3, Jen-Hsiang Tsai4
1Institute of Molecular Biology College of Life Science, National Chung Hsing University, Taichung, Taiwan.
Abstract:
Treatment of advanced hepatocellular carcinoma (HCC) has exhibited a poor overall survival rate of only six to ten months, and the urgency of the development of more effective novel agents is ever present. In this line of research, we aimed to investigate the effects and inhibitive mechanisms of aqueous Ocimum gratissimum leaf extract (OGE), the extract of Ocimum gratissimum, which is commonly used as a therapeutic herb for its numerous pharmacological properties, on malignant HCC cells. Our results showed that OGE decreased the cell viability of HCC SK-Hep1 and HA22T cells in a dose-dependent manner (from 400 to 800 µg/mL), while there is little effect on Chang liver cells. Moreover, cell-cycle analysis shows increased Sub-G1 cell count in SK-Hep1 and HA22T cells which is not observed in Chang liver cells. These findings raise suspicion that the OGE-induced cell death may be mediated through proteins that regulate cell cycle and apoptosis in SK-Hep1 and HA22T cells, and further experimentation revealed that OGE treatment resulted in a dose-dependent decrease in caspase 3 and PARP expressions and in CDK4and p-ERK1/2expressions. Moreover, animal tests also exhibited decreased HCC tumor growth by OGE treatment. We therefore suggest that the inhibition of cell viability and tumor growth induced by OGE may be correlated to the alteration of apoptosis-related proteins.
Insights
Aqueous Ocimum gratissimum leaf extract (OGE) effectively reduced hepatocellular carcinoma (HCC) cell viability and tumor growth. OGE demonstrated potential as a novel therapeutic agent by modulating apoptosis-related proteins.
Area of Science:
- Oncology
- Pharmacology
- Natural Products
Background:
- Advanced hepatocellular carcinoma (HCC) has a poor prognosis with limited treatment options.
- Novel therapeutic agents are urgently needed to improve survival rates for HCC patients.
Purpose of the Study:
- To investigate the anti-cancer effects of aqueous Ocimum gratissimum leaf extract (OGE) on malignant HCC cells.
- To elucidate the mechanisms underlying OGE's inhibitory effects on HCC progression.
Main Methods:
- In vitro studies using HCC cell lines (SK-Hep1, HA22T) and normal liver cells (Chang liver).
- Cell viability assays, cell cycle analysis, and Western blot analysis for apoptosis and cell cycle regulatory proteins (caspase 3, PARP, CDK4, p-ERK1/2).
- In vivo animal models to assess OGE's effect on HCC tumor growth.
Main Results:
- OGE significantly decreased HCC cell viability in a dose-dependent manner, with minimal impact on normal liver cells.
- Cell cycle analysis revealed an increase in Sub-G1 cell count in HCC cells, indicating apoptosis induction.
- OGE treatment led to a dose-dependent decrease in caspase 3, PARP, CDK4, and p-ERK1/2 expressions.
- Animal studies confirmed that OGE treatment reduced HCC tumor growth.
Conclusions:
- OGE exhibits significant anti-cancer properties against hepatocellular carcinoma.
- The anti-tumor effects of OGE are mediated through the induction of apoptosis and modulation of key cell cycle and apoptosis-related proteins.
- OGE shows promise as a potential therapeutic agent for advanced HCC.
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