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Modulation of NDEA activated ras expression and protein kinase C activity by nicotinamide
S Choudhury1, M Krishna, R K Bhattacharya
1Radiation Biology Division, Bhabha Atomic Research Centre, Mumbai, India.
Abstract:
Nicotinamide, an amide derivative of vitamin B3, was found to inhibit the increase in ras expression, protein kinase C (PKC) activity, and diacylglycerol (DAG) levels in rats treated with N-nitrosodiethylamine (NDEA). It effectively modulated the carcinogen induced increase in the cytosol and the particulate PKC activities but not the nuclear PKC activity. The DAG levels were also modulated by the endobiotic. It may serve as an ideal modulator of carcinogenesis. Nicotinamide is currently under trial as a radio sensitizer, and inhibition of these parameters may be one of the ways in which it confers radiosensitivity.
Insights
Nicotinamide, a vitamin B3 derivative, inhibits key molecules like ras expression and protein kinase C (PKC) activity in rats exposed to a carcinogen. This modulation suggests its potential role in cancer prevention and radiosensitization.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Carcinogenesis involves complex molecular pathways.
- Nicotinamide (vitamin B3) is being investigated for therapeutic potential.
- Ras expression, protein kinase C (PKC), and diacylglycerol (DAG) are implicated in cancer development.
Purpose of the Study:
- To investigate the effects of nicotinamide on specific molecular markers during N-nitrosodiethylamine (NDEA)-induced carcinogenesis in rats.
- To determine if nicotinamide can modulate key signaling pathways involved in cancer initiation.
Main Methods:
- Rats were treated with N-nitrosodiethylamine (NDEA) to induce carcinogenesis.
- Nicotinamide was administered to assess its impact on ras expression, PKC activity, and DAG levels.
- PKC activity was measured in cytosolic, particulate, and nuclear fractions.
Main Results:
- Nicotinamide significantly inhibited the NDEA-induced increase in ras expression, PKC activity, and DAG levels.
- It modulated PKC activity in cytosolic and particulate fractions but not in the nuclear fraction.
- Nicotinamide effectively modulated endobiotic DAG levels.
Conclusions:
- Nicotinamide demonstrates potential as a modulator of carcinogenesis by inhibiting key molecular events.
- Its ability to interfere with these pathways may contribute to its efficacy as a radiosensitizer.
- Further research into nicotinamide's role in cancer prevention and therapy is warranted.