Oleanolic Acid Suppressed DMBA-Induced Liver Carcinogenesis through Induction of Mitochondrial-Mediated Apoptosis and
Samar Hosny1, Heba Sahyon2, Magdy Youssef1
1Chemistry Department, Biochemistry Division, Faculty of Science, Mansoura University, Mansoura, Egypt.
Abstract:
Phytochemicals appeared as a rich source of efficient and safe agents against many diseases like cancer. Various herbal sources are rich in oleanolic acid (OA). The scope of this study was to assess the biochemical and molecular mechanisms implicated in the ameliorative potency of OA against DMBA-induced liver carcinogenesis. Forty-eight male albino mice were assigned randomly to five groups (eight mice each) as follows: control healthy group, olive oil group, OA group, DMBA group, and DMBA with OA. Apoptosis, autophagy, inflammation, proliferation, and angiogenesis were investigated in the tissue samples. Histopathological examination was carried out as well as liver enzymes activity and other hepatic antioxidant and inflammatory biomarkers. The treatment with OA effectively suppressed the DMBA-initiated liver carcinogenesis via modulation of antioxidant status, induction of apoptosis and autophagy through modulating the expression of Caspase-3, Bcl-2 and Beclin-1, inhibiting angiogenesis (VEGF), proliferation (PCNA), and improved liver function and histological picture with a reduction in AFP level. Additionally, OA applies its antitumor effects by inhibition of proinflammatory transcription factor NF-κB and inflammatory markers (TNF-α and Cox-2) associated with DMBA administration. The present study shows that OA treatment efficiently suppressed the DMBA-initiated liver carcinogenesis through induction of mitochondrial-mediated apoptosis and autophagy and modulating inflammation.
Insights
Oleanolic acid (OA) effectively combats liver cancer initiated by DMBA in mice. OA suppresses tumor growth by promoting apoptosis and autophagy while reducing inflammation and angiogenesis.
Area of Science:
- Phytochemistry
- Hepatology
- Molecular Biology
- Cancer Research
Background:
- Phytochemicals, including oleanolic acid (OA) found in herbs, show promise as safe and effective anti-cancer agents.
- Liver carcinogenesis, often induced by chemicals like DMBA, remains a significant health concern.
- Understanding the molecular mechanisms of phytochemicals against liver cancer is crucial for developing new therapies.
Purpose of the Study:
- To investigate the biochemical and molecular mechanisms underlying the protective effects of oleanolic acid (OA) against DMBA-induced liver carcinogenesis.
- To evaluate OA's impact on key cellular processes including apoptosis, autophagy, inflammation, proliferation, and angiogenesis in a mouse model.
Main Methods:
- A mouse model of DMBA-induced liver carcinogenesis was established.
- Mice were treated with oleanolic acid (OA), and various parameters were assessed, including histopathology, liver enzymes, antioxidant and inflammatory biomarkers.
- Molecular mechanisms were explored by examining the expression of apoptosis (Caspase-3, Bcl-2), autophagy (Beclin-1), proliferation (PCNA), angiogenesis (VEGF), and inflammation (NF-κB, TNF-α, Cox-2) markers.
Main Results:
- Oleanolic acid (OA) significantly suppressed DMBA-induced liver carcinogenesis.
- OA treatment modulated antioxidant status, induced apoptosis and autophagy (via Caspase-3, Bcl-2, Beclin-1), inhibited proliferation (PCNA) and angiogenesis (VEGF).
- OA improved liver function, reduced alpha-fetoprotein (AFP) levels, and inhibited pro-inflammatory markers (NF-κB, TNF-α, Cox-2).
Conclusions:
- Oleanolic acid (OA) demonstrates potent anti-tumor effects against DMBA-induced liver carcinogenesis in mice.
- OA exerts its protective effects by inducing mitochondrial-mediated apoptosis and autophagy, and by modulating inflammatory pathways.
- OA represents a promising natural compound for the prevention and treatment of liver cancer.
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