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Published on: October 30, 2013
Iminoflavones combat 1,2-dimethyl hydrazine-induced aberrant crypt foci development in colon cancer
V Ganga Prasad1, Shishir Kawade2, B S Jayashree2
1Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, Karnataka 576104, India.
Abstract:
The aim of the present study was to evaluate the antitumor potential of iminoflavones in in vitro and in vivo anticancer models. Preliminary screening in various cancer cell lines revealed four potential iminoflavones out of which IMF-8 was taken based on its activity against colon cancer cells. This was further confirmed by observing the nuclear changes in the cells by AO/EB and Hoechst 33342 staining studies. In vivo activity was assessed by dimethyl hydrazine-(DMH-) induced colon cancer model in rats. Animals were administered DMH (20 mg/kg, b.w. for 10 weeks and 30 mg/kg b.w., i.p. for 10 weeks) and were supplemented with (IMF-8) iminoflavone-8 (200 mg/kg, p.o. for 14 days). Results showed that DMH induced 100% aberrant crypt foci (ACF) and polyps which were significantly reduced in the IMF-8 treated group. IMF-8 significantly increased the catalase and GSH levels whereas it reduced the TNF- α and IL-6 levels markedly which suggests the antioxidative and anti-inflammatory actions of flavonoids present in IMF-8. The histopathological images of the IMF-8 treated colon showed no signs of mucosal crypt abscess. These findings suggest that the semi-synthetic iminoflavones, IMF-8, effectively inhibit DMH-induced ACFs and colonic crypts by alleviating the oxidative stress and suppressing the inflammation.
Insights
This study shows iminoflavone-8 (IMF-8) effectively combats colon cancer by reducing aberrant crypt foci and polyps. IMF-8 demonstrates antioxidant and anti-inflammatory properties, offering a promising natural compound for cancer prevention.
Area of Science:
- Pharmacology
- Oncology
- Natural Product Chemistry
Background:
- Colon cancer remains a significant global health challenge.
- Aberrant crypt foci (ACF) and polyps are early indicators of colorectal cancer.
- Natural compounds are being explored for their chemopreventive potential.
Purpose of the Study:
- To evaluate the antitumor potential of semi-synthetic iminoflavones against colon cancer.
- To investigate the efficacy of iminoflavone-8 (IMF-8) in both in vitro and in vivo models.
- To elucidate the antioxidative and anti-inflammatory mechanisms of IMF-8.
Main Methods:
- Screening of iminoflavones in various cancer cell lines.
- In vitro validation using AO/EB and Hoechst 33342 staining for nuclear changes.
- In vivo assessment using a dimethyl hydrazine (DMH)-induced rat colon cancer model.
Main Results:
- IMF-8 demonstrated significant activity against colon cancer cells in vitro.
- IMF-8 treatment markedly reduced DMH-induced aberrant crypt foci (ACF) and polyps in rats.
- IMF-8 elevated antioxidant markers (catalase, GSH) and reduced inflammatory markers (TNF-α, IL-6).
Conclusions:
- Semi-synthetic iminoflavone-8 (IMF-8) exhibits significant antitumor effects against DMH-induced colon cancer.
- IMF-8 alleviates oxidative stress and suppresses inflammation, contributing to its chemopreventive action.
- IMF-8 shows promise as a therapeutic agent for colon cancer prevention and treatment.

