title: D-pinitol mitigates tumor growth by modulating interleukins and hormones and induces apoptosis in rat breast carcinogenesis through inhibition of NF-κB.
abstract: Breast cancer is the most prevalent malignant neoplasm in the world, and chemoprevention through dietary intervention strategy is an emerging option to reduce the incidence. D-pinitol (DP), a major component of soya bean, possesses attractive biological actions. We have investigated whether D-pinitol have an effect on tumor growth in vivo against 7,12-dimethylbenz(a)anthracene (DMBA)-initiated rat mammary carcinogenesis and investigated its mechanism of action. Tumors were induced in Sprague-Dawley (SD) rats by a gastric dose of 20 mg/kg DMBA, and after 13 weeks of induction period, the rats were orally administered with D-pinitol for 45 days. At the end of the assay, animals in carcinogen control group prompted a tumor incidence of 100 % and developed a tumor volume of 8.35 ± 0.56, which was significantly reduced to 5.74 ± 0.32 for the animals treated with D-pinitol. The D-pinitol treatment not only decreased the tumor volume but also further examination revealed that tumors from animals that received D-pinitol reduced nuclear factor kappa B (NF-κB) activation which in turn results in modulation of its downstreaming p53 and proteins of caspase-3 family. Bcl-2 expression and caspase-3 activation were also decreased after D-pinitol supplementation leading to induction of apoptosis and finally cell death. Furthermore, the status of the inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin (IL)-2, IL-6, and tumor markers, lipid profile, and hormones was also significantly declined up on D-pinitol administration. Thus, it reveals the collective involvement of the above-mentioned parameters along with NF-κB signaling through which D-pinitol induces apoptosis and subsequently suppresses breast cancer during DMBA-induced rat breast carcinogenesis.
authors.affiliation: Department of Chemical Pathology, School of Medical Sciences, Universiti Sains Malaysia, Health Campus, Kelantan, Malaysia, 16150.
authors.forename: Thamaraiselvan
authors.initials: T
authors.lastname: Rengarajan
authors.forename: Natarajan
authors.initials: N
authors.lastname: Nandakumar
authors.forename: Peramaiyan
authors.initials: P
authors.lastname: Rajendran
authors.forename: Mohanraj Karthik
authors.initials: MK
authors.lastname: Ganesh
authors.forename: Maruthaiveeran Periyasamy
authors.initials: MP
authors.lastname: Balasubramanian
authors.forename: Ikuo
authors.initials: I
authors.lastname: Nishigaki
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D014408:Biomarkers, Tumor / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006728:Hormones / Q000378:metabolism*; D007136:Immunoglobulins / Q000378:metabolism; D007294:Inositol / Q000031:analogs & derivatives* / Q000494:pharmacology; D007378:Interleukins / Q000378:metabolism*; D050356:Lipid Metabolism / Q000187:drug effects; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C494828:Bax protein, rat; D014408:Biomarkers, Tumor; D016207:Cytokines; D006728:Hormones; D007136:Immunoglobulins; D007378:Interleukins; D016328:NF-kappa B; D051028:bcl-2-Associated X Protein; C021730:pinitol; D007294:Inositol; D015127:9,10-Dimethyl-1,2-benzanthracene
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