title: Iminoflavones combat 1,2-dimethyl hydrazine-induced aberrant crypt foci development in colon cancer.
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.
authors.affiliation: Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, Karnataka 576104, India.
authors.forename: V Ganga
authors.initials: VG
authors.lastname: Prasad
authors.affiliation: Department of Pharmaceutical Chemistry, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, Karnataka 576104, India.
authors.forename: Shishir
authors.initials: S
authors.lastname: Kawade
authors.affiliation: Department of Pharmaceutical Chemistry, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, Karnataka 576104, India.
authors.forename: B S
authors.initials: BS
authors.lastname: Jayashree
authors.affiliation: Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, Karnataka 576104, India.
authors.forename: Neetinkumar D
authors.initials: ND
authors.lastname: Reddy
authors.affiliation: Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, Karnataka 576104, India.
authors.forename: Albi
authors.initials: A
authors.lastname: Francis
authors.affiliation: Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, Karnataka 576104, India.
authors.forename: Pawan G
authors.initials: PG
authors.lastname: Nayak
authors.affiliation: Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, Karnataka 576104, India.
authors.forename: Anoop
authors.initials: A
authors.lastname: Kishore
authors.affiliation: Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, Karnataka 576104, India.
authors.forename: K
authors.initials: K
authors.lastname: Nandakumar
authors.affiliation: Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, Karnataka 576104, India.
authors.forename: C Mallikarjuna
authors.initials: CM
authors.lastname: Rao
authors.affiliation: Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, Karnataka 576104, India.
authors.forename: Rekha R
authors.initials: RR
authors.lastname: Shenoy
mesh_terms: D019813:1,2-Dimethylhydrazine / Q000633:toxicity; D058739:Aberrant Crypt Foci / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D000818:Animals; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D047309:Flavones / Q000008:administration & dosage*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis; D015227:Lipid Peroxidation / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D047309:Flavones; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D019813:1,2-Dimethylhydrazine; C043562:flavone