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Cardamonin inhibits colonic neoplasia through modulation of MicroRNA expression
Shirley James1, Jayasekharan S Aparna1, Aswathy Mary Paul2
1Cancer Research Program, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala State, 695014, India.
Abstract:
Colorectal cancer is currently the third leading cause of cancer related deaths. There is considerable interest in using dietary intervention strategies to prevent chronic diseases including cancer. Cardamonin is a spice derived nutraceutical and herein, for the first time we evaluated the therapeutic benefits of cardamonin in Azoxymethane (AOM) induced mouse model of colorectal cancer. Mice were divided into 4 groups of which three groups were given six weekly injections of AOM. One group served as untreated control and remaining groups were treated with either vehicle or Cardamonin starting from the same day or 16 weeks after the first AOM injection. Cardamonin treatment inhibited the tumor incidence, tumor multiplicity, Ki-67 and β-catenin positive cells. The activation of NF-kB signaling was also abrogated after cardamonin treatment. To elucidate the mechanism of action a global microRNA profiling of colon samples was performed. Computational analysis revealed that there is a differential expression of miRNAs between these groups. Subsequently, we extend our findings to human colorectal cancer and found that cardamonin inhibited the growth, induces cell cycle arrest and apoptosis in human colorectal cancer cell lines. Taken together, our study provides a better understanding of chemopreventive potential of cardamonin in colorectal cancer.
Insights
Cardamonin, a compound from spices, shows promise in preventing colorectal cancer. This study found it reduced tumor development and growth in mice and human cancer cells.
Area of Science:
- Oncology
- Molecular Biology
- Nutraceutical Research
Background:
- Colorectal cancer is a leading cause of cancer deaths globally.
- Dietary interventions are explored for cancer prevention.
- Cardamonin is a nutraceutical derived from spices with potential anti-cancer properties.
Purpose of the Study:
- To investigate the therapeutic and chemopreventive effects of cardamonin.
- To evaluate cardamonin in an Azoxymethane (AOM)-induced mouse model of colorectal cancer.
- To explore the molecular mechanisms underlying cardamonin's action.
Main Methods:
- Azoxymethane (AOM) induced colorectal cancer model in mice.
- Treatment with cardamonin at different time points relative to AOM injection.
- Analysis of tumor incidence, multiplicity, and cell proliferation markers (Ki-67, β-catenin).
- NF-kB signaling pathway assessment.
- Global microRNA profiling of colon tissues.
- In vitro studies on human colorectal cancer cell lines.
Main Results:
- Cardamonin significantly inhibited tumor incidence and multiplicity in the AOM-induced mouse model.
- Treatment reduced the number of Ki-67 and β-catenin positive cells, indicating decreased proliferation.
- Cardamonin abrogated the activation of NF-kB signaling.
- MicroRNA profiling revealed differential expression patterns.
- In human colorectal cancer cell lines, cardamonin inhibited growth, induced cell cycle arrest, and promoted apoptosis.
Conclusions:
- Cardamonin exhibits significant chemopreventive potential against colorectal cancer.
- The compound acts by inhibiting proliferation, modulating signaling pathways (NF-kB), and affecting microRNA expression.
- These findings support cardamonin as a potential dietary intervention for colorectal cancer prevention.
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