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Fish oil prevents colon cancer by modulation of structure and function of mitochondria
Navneet Agnihotri1, Gayatri Sharma1, Isha Rani1
1Department of Biochemistry, Panjab University, Chandigarh 160014, India.
Abstract:
Cancer cells are more susceptible to metabolic perturbations due to impaired electron transport chain (ETC) that promote uncontrolled proliferation. Mitochondria play a pivotal role in bioenergetics and apoptosis, hence are considered as a promising target in tumor cell eradication. Therefore, the present study is designed to elucidate chemopreventive action of fish oil (FO) in combination with corn oil (CO) on mitochondria in colorectal cancer (CRC). Male Wistar rats were divided into groups depending on dietary regimen-Control group, FO+CO(1:1) and FO+CO(2.5:1). These groups were further subdivided depending on whether these received a weekly intraperitoneal injection of ethylenediamine tetra-acetic acid (EDTA) or N,N-dimethylhydrazine dihydrochloride (DMH) for a period of 4 weeks. The animals sacrificed 48h and 16 weeks after EDTA/DMH treatment constituted initiation and post-initiation phase respectively. The structural and functional alterations in mitochondria were evaluated using transmission electron microscopy (TEM) and by assaying electron transport chain (ETC) enzymes. Mitochondrial lipid composition and cholesterol levels were also assessed. DMH treatment led to mitochondrial degeneration, disrupted cristae and a significant decrease in ETC complexes suggestive of metabolic reprogramming. Moreover, an increase in cholesterol and cardiolipin (CL) levels in post-initiation phase led to evasion of apoptosis. FO in both the ratios resulted in stabilization and increase in number of mitochondria, however, FO+CO(2.5:1)+DMH group also exhibited mitophagy and crystolysis alongwith altered dynamics in ETC which facilitated apoptosis. It also decreased cholesterol and CL levels to increase apoptosis. Fish oil targets mitochondria in a dose dependent manner that augments apoptosis and hence attenuates carcinogenesis.
Insights
Fish oil, combined with corn oil, targets mitochondria to enhance apoptosis and reduce colorectal cancer (CRC) development. This dietary intervention shows promise in cancer prevention by modulating mitochondrial function.
Area of Science:
- Mitochondrial biology
- Cancer research
- Nutritional science
Background:
- Cancer cells exhibit metabolic vulnerabilities due to impaired electron transport chain (ETC) function.
- Mitochondria are crucial for cellular energy production and programmed cell death (apoptosis), making them a key target for cancer therapy.
- Colorectal cancer (CRC) progression involves mitochondrial dysfunction.
Purpose of the Study:
- To investigate the chemopreventive effects of fish oil (FO) and corn oil (CO) on mitochondria in a rat model of colorectal cancer (CRC).
- To elucidate the mechanisms by which dietary oils modulate mitochondrial structure, function, and lipid composition during carcinogenesis.
Main Methods:
- Rats were administered diets with varying ratios of FO and CO (1:1 and 2.5:1) and treated with N,N-dimethylhydrazine dihydrochloride (DMH) or ethylenediamine tetra-acetic acid (EDTA).
- Mitochondrial integrity was assessed using transmission electron microscopy (TEM).
- Electron transport chain (ETC) enzyme activity, mitochondrial lipid composition (cholesterol and cardiolipin), and apoptosis markers were evaluated at different time points.
Main Results:
- DMH-induced CRC led to mitochondrial damage, decreased ETC complex activity, and increased cholesterol and cardiolipin levels, promoting apoptosis evasion.
- Fish oil, particularly at a 2.5:1 ratio with corn oil, stabilized mitochondria, increased their numbers, and reduced cholesterol and cardiolipin levels.
- The FO+CO(2.5:1) combination promoted mitophagy and altered ETC dynamics, facilitating apoptosis and attenuating CRC development.
Conclusions:
- Fish oil demonstrates a dose-dependent, chemopreventive effect against colorectal cancer by targeting mitochondria.
- Dietary intervention with fish oil enhances mitochondrial function and promotes apoptosis, offering a potential strategy for cancer attenuation.
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