Dietary Diindolylmethane Enhances the Therapeutic Effect of Centchroman in Breast Cancer by Inhibiting Neoangiogenesis.

Dhanamjai, Penta and Jagadish, Natesh and Priya, Mondal and Meeran, Syed Musthapa (2022) Dietary Diindolylmethane Enhances the Therapeutic Effect of Centchroman in Breast Cancer by Inhibiting Neoangiogenesis. Nutrition and Cancer.

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Abstract

Tumor angiogenesis is primarily regulated by vascular endothelial growth factor and its receptor (VEGF-VEGFR) communication, which is involved in cancer cell growth, progression, and metastasis. Diindolylmethane (DIM), a dietary bioactive from cruciferous vegetables, has been extensively studied in preclinical models for breast cancer prevention and treatment. Nevertheless, the possible role of DIM in the angiogenesis and metastasis regulations in triple-negative breast cancer (TNBC) remains elusive. Here, we investigated the potential anti-angiogenic and anti-metastatic role of DIM in combination with centchroman (CC). We observed that the oral administration of the DIM and CC combination suppressed primary tumor growth and tumor-associated vascularization in 4T1 tumors. Further, the DIM and CC combination exhibited a strong inhibitory effect on VEGF-induced angiogenesis in matrigel plugs. The mechanistic study demonstrated that DIM and CC could effectively downregulate VEGFA expression in tumor tissue and strongly interact with VEGFR2 to block its kinase activity. Interestingly, the DIM and CC combination also suppressed the lung metastasis of the highly metastatic 4T1 tumors through the downregulation of FAK/MMP9/2 signaling and reversal of epithelial-to-mesenchymal transition (EMT). Overall, these findings suggest that DIM-based nutraceuticals and functional foods can be developed as adjuvant therapy for treating TNBC.

Item Type:	Article
Uncontrolled Keywords:	triple-negative breast cancer, Diindolylmethane (DIM), dietary bioactive, cruciferous vegetables
Subjects:	600 Technology > 01 Medical sciences > 09 Human Physiology 600 Technology > 08 Food technology > 23 Vegetables
Divisions:	Dept. of Biochemistry
Depositing User:	Food Sci. & Technol. Information Services
Date Deposited:	19 May 2023 11:14
Last Modified:	19 May 2023 11:14
URI:	http://ir.cftri.res.in/id/eprint/16430

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