Thamaraiselvan Rengarajan, Natarajan Nandakumar, Peramaiyan Rajendran, Mohanraj Karthik Ganesh, Maruthaiveeran Periyasamy Balasubramanian, Ikuo Nishigaki
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 abovementioned parameters along with NF-κB signaling through which d-pinitol induces apoptosis and subsequently suppresses breast cancer during DMBA-induced rat breast carcinogenesis.
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