Docosahexaenoic Acid (DHA) Inhibits Bone Morphogenetic Protein-2 (BMP-2) Elevated Osteoblast Potential of Metastatic Breast Cancer (MDA-MB-231) Cells in Mammary Microcalcification

Abstract

Microcalcification seems to be an assurance signature for the prediction of breast cancer malignancy. However, neither systematic study for deciphering the molecular mechanism of mammary microcalcification has yet been conducted, nor a mechanistic study has been performed to find out its prevention. Thus, this study firstly aimed at determining if malignant breast tissues/metastatic breast cancer cells exhibit elevated intrinsic osteoblast-like potential responsible for driving the pathological microcalcification in breast tumors. Here, tumor sample analysis showed higher levels of various osteogenic genes (e.g., Runx2, osterix), and increased ALP activity and calcification in malignant breast tissues when compared to benign tissues, indicating the existence of elevated osteoblast-like potential in malignant breast tissues as compared to benign tissues. Similarly, cell culture study found that metastatic MDA-MB-231 cells acquired a higher osteoblast-like potential as compared to less metastatic breast cancer MCF-7 cells. It was also noticed that osteoinducer bone morphogenetic protein 2 (BMP-2) increased osteoblast-like differentiation and calcification potential in breast cancer cells. Moreover, omega-3 fatty acid docosahexaenoic acid (DHA) showed an inhibitory effect on BMP-2 induced osteoblast-like potential presumably by abrogating BMP signaling. Thus, this study for the first time unraveled that DHA may mitigate microcalcification by blocking osteoblast-like potential of breast cancer cells.

Acknowledgments

The authors acknowledge JLN hospital, Ajmer, India, for providing human samples. The authors thank Prof. Alo Nag, University of Delhi South Campus, Delhi, India, for providing some reagents.

Disclosure Statement

The authors report no conflict of interest in this study.

Additional information

Funding

C.C.M. is supported by UGC Grant [30-49/2014 (BSR)], DBT [6242 P9/RGCB/PMD/DBT/CCML/2015], Indo-Russia project [INT/RUS/RFBR/P-256] and Central University of Rajasthan, India, and T.S. is supported by DST-INSPIRE fellowship [IF140765] provided by DST, India.