J Cancer Prev 25(1): 1-12

Diallyl Trisulfide Inhibits Leptin-induced Oncogenic Signaling in Human Breast Cancer Cells but Fails to Prevent Chemically-induced Luminal-type Cancer in Rats

Department of Pharmacology and Chemical Biology, UPMC Hillman Cancer Center, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

Correspondence to Shivendra V. Singh, E-mail: ude.cmpu@shgnis, https://orcid.org/0000-0002-3733-144X

Received 2020 Mar 10; Revised 2020 Mar 17; Accepted 2020 Mar 17.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Previous studies have demonstrated inhibitory effect of garlic component diallyl trisulfide (DATS) on growth of breast cancer cells in vitro and in vivo. This study investigated the effect of DATS on oncogenic signaling regulated by leptin, which plays an important role in breast carcinogenesis. Leptin-induced phosphorylation and nuclear translocation of STAT3 was inhibited significantly in the presence of DATS in MCF-7 (a luminal-type human breast cancer cell line) and MDA-MB-231 (a basal-like human breast cancer cell line). Leptin-stimulated cell proliferation, clonogenic cell survival, and migration and/or invasion ability in MCF-7 and/or MDA-MB-231 cells were also suppressed by DATS treatment. DATS exposure resulted in inhibition of leptin-stimulated expression of protein and/or mRNA levels of Bcl-2, Bcl-xL, Cyclin D1, vascular endothelial growth factor, and matrix metalloproteinase-2. Western blotting revealed a decrease in protein levels of phosphorylated STAT3 in breast cancer xenografts from DATS-treated mice when compared to controls in vivo. However, the incidence of N-methyl-N-nitrosourea-induced luminal-type breast cancer development in rats was not affected by oral administration of 5 mg/kg or 25 mg/kg DATS. The present study reveals that oncogenic signaling induced by leptin is inhibited in the presence of DATS but higher doses of this phytochemical may be required to achieve chemopreventive activity.

Keywords: Breast cancer, Leptin, STAT3, Diallyl trisulfide, Chemoprevention

Abstract

ACKNOWLEDGMENTS

This study was supported by the USPHS grant RO1 CA219180 awarded by the National Cancer Institute. This research used the Flow Cytometry Facility and the Tissue and Research Pathology Facility supported in part by Cancer Center Support Grant from the National Cancer Institute (P30 CA047904).

ACKNOWLEDGMENTS

Footnotes

CONFLICTS OF INTEREST

No potential conflicts of interest were disclosed.

Footnotes

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