D-pinitol mitigates tumor growth by modulating interleukins and hormones and induces apoptosis in rat breast carcinogenesis through inhibition of NF-κB

J Physiol Biochem. 2015 Jun;71(2):191-204. doi: 10.1007/s13105-015-0397-9. Epub 2015 Apr 1.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 9,10-Dimethyl-1,2-benzanthracene / toxicity
  • Animals
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Biomarkers, Tumor / metabolism
  • Cytokines / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Hormones / metabolism*
  • Immunoglobulins / metabolism
  • Inositol / analogs & derivatives*
  • Inositol / pharmacology
  • Interleukins / metabolism*
  • Lipid Metabolism / drug effects
  • Mammary Neoplasms, Experimental / chemically induced
  • Mammary Neoplasms, Experimental / drug therapy*
  • Mammary Neoplasms, Experimental / metabolism
  • Mammary Neoplasms, Experimental / pathology
  • NF-kappa B / antagonists & inhibitors*
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Rats, Sprague-Dawley
  • bcl-2-Associated X Protein / metabolism

Substances

  • Antineoplastic Agents
  • Bax protein, rat
  • Biomarkers, Tumor
  • Cytokines
  • Hormones
  • Immunoglobulins
  • Interleukins
  • NF-kappa B
  • bcl-2-Associated X Protein
  • pinitol
  • Inositol
  • 9,10-Dimethyl-1,2-benzanthracene