Diindolylmethane Promotes Metabolic Crisis and Enhances the Efficacy of Centchroman in Breast Cancer: A 1 H NMR-Based Approach.

Dhanamjai, Penta and Pratima, Tripathi and Dheeran, R. and Jagadish, Natesh and Priya, Mondal and Meeran, Syed Musthapa (2022) Diindolylmethane Promotes Metabolic Crisis and Enhances the Efficacy of Centchroman in Breast Cancer: A 1 H NMR-Based Approach. ACS Omega, 7 (47). pp. 43147-43160.

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Abstract

Diindolylmethane (DIM) is a key metabolite of indole-3- carbinol found in cruciferous vegetables such as broccoli, cauliflower, and cabbage. DIM has been known for its anti-cancerous activity through various mechanisms. Most cancer cells, including triple-negative breast cancer (TNBC), adapt distinct metabolic reprogramming for rapid growth and proliferation. Hence, targeting metabolic dysregulation may provide a favorable therapeutic condition for the treatment of TNBC. Earlier, we found that DIM increases the intracellular accumulation of Centchroman (CC), a potential anticancer agent, thereby enhancing the therapeutic potential of CC against breast cancer. However, the role of DIM in regulating TNBC cellular metabolism remains unknown. In the current study, we investigated the potential therapeutic interventions of DIM in TNBC and its metabolic reprogramming in enhancing the efficacy of CC. We found that DIM induced metabolic catastrophe in TNBC cells by regulating aerobic glycolysis and intermediate metabolism. Further, the DIM and CC combination significantly inhibited the TNBC tumor growth in the 4T1-syngeneic model. The inhibition of tumor growth was associated with the downregulation of key aerobic glycolysis mediators such as PKM2, GLUT1, and hypoxia-inducible factor 1α (HIF-1α). This is a first-of-a-kind investigation linking DIM with aerobic glycolysis regulation and enhancing the treatment efficacy of CC against TNBC. Therefore, these findings suggest that DIM-based nutraceuticals and functional foods can be developed as adjuvant therapy for treating metabolically dysregulated TNBC

Item Type:	Article
Uncontrolled Keywords:	Diindolylmethane, DIM-based nutraceuticals, functional foods, breast cancer
Subjects:	600 Technology > 01 Medical sciences > 13 Nutrition-Human 600 Technology > 08 Food technology > 23 Vegetables
Divisions:	Dept. of Biochemistry
Depositing User:	Food Sci. & Technol. Information Services
Date Deposited:	19 May 2023 10:59
Last Modified:	19 May 2023 10:59
URI:	http://ir.cftri.res.in/id/eprint/16427

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