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

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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 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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Acknowledgments

The authors are extremely grateful to Dr. R. Venkatakrishna Murali, M.D., Ph.D., Professor and Head, Department of Pharmacology and Environmental Toxicology, Dr. A.L. Mudhaliar Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani, Chennai—600113 for providing the laboratory facilities and the financial assistance from Department of Science and Technology (DST), New Delhi in the form of DST-PURSE-JRF is gratefully acknowledged and one of the authors “Natarajan Nandakumar” thank Prof. Jacob Gopas PhD, MPH (BGU, Israel) for his useful comments and encouragement. We thank Dr. S. Prakash, Ph.D., Assistant Professor, Department of Anatomy, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani, Chennai for interpreting the immunofluorescence micrographs and suggestions. We are also thankful to Mrs. Rita Rajan, CMC Vellore for transmission electron microscope studies and Dr. Sarasabharathy for interpretation.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Chemical Pathology, School of Medical Sciences, Universiti Sains Malaysia, Health Campus, Kelantan, Malaysia, 16150

    Thamaraiselvan Rengarajan

  2. Department of Pharmacology and Environmental Toxicology, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai, 600113, Tamil Nadu, India

    Thamaraiselvan Rengarajan, Natarajan Nandakumar & Maruthaiveeran Periyasamy Balasubramanian

  3. NPO-International Laboratory of Biochemistry, 1-166, Uchide, Nakagawa-ku, Nagoya, 454-0926, Japan

    Peramaiyan Rajendran & Ikuo Nishigaki

  4. The Shraga Segal Department of Microbiology, Immunology and Genetics, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva, Israel

    Natarajan Nandakumar

  5. Department of Anatomy, Dr. ALM PG IBMS, University of Madras, Chennai, 600113, Tamil Nadu, India

    Mohanraj Karthik Ganesh

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  1. Thamaraiselvan Rengarajan
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Rengarajan, T., Nandakumar, N., Rajendran, P. et al. 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 71, 191–204 (2015). https://doi.org/10.1007/s13105-015-0397-9

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