BDMC-A, an analog of curcumin, inhibits markers of invasion, angiogenesis, and metastasis in breast cancer cells via NF-κB pathway--A comparative study with curcumin.
Breast cancer chemoprevention has become increasingly important in India as it faces a potential breast cancer epidemic over the next decade. Curcumin, the active ingredient in turmeric is a well known chemopreventive agent that possesses various therapeutic properties including antioxidants and anti-inflammatory effects. In the present study, we have investigated the inhibitory effects of BDMC-A, an analog of curcumin, on invasion, angiogenesis and metastasis markers using in vitro with MCF-7 cells and in silico studies, hence proved that BDMC-A has more potential than curcumin. Mechanistic studies revealed that BDMC-A might have exerted its activity by inhibiting metastatic and angiogenic pathways by modulating the expression of proteins upstream to NF-κB (TGF-β, TNF-α, IL-1β and c-Src), and NF-κB signaling cascade (c-Rel, COX-2, MMP-9, VEGF, IL-8) and by upregulating TIMP-2 levels. An in silico molecular docking study with NF-κB revealed that the docking score and interaction of BDMC-A with NF-κB-DNA binding was more efficient when compared to curcumin. Our overall results showed that BDMC-A more effectively inhibited invasion, angiogenesis and metastasis markers compared to curcumin. The activity can be attributed to the presence of hydroxyl group in the ortho position in its structure. Further research are going on to prove its potential as a therapeutic agent for breast cancer.
Department of Biochemistry and Molecular Biology, School of Life Sciences, Pondicherry University, Puducherry 605 014, India.
Kumaravel
K
Mohankumar
Department of Biochemistry and Molecular Biology, School of Life Sciences, Pondicherry University, Puducherry 605 014, India.
Subhashree
S
Sridharan
Department of Biochemistry and Molecular Biology, School of Life Sciences, Pondicherry University, Puducherry 605 014, India.
Sankar
S
Pajaniradje
Centre for Bioinformatics, School of Life Sciences, Pondicherry University, Puducherry 605 014, India.
Vivek Kumar
VK
Singh
Virology Laboratory-II, National Institute of Immunology, New Delhi, India.
Larance
L
Ronsard
Virology Laboratory-II, National Institute of Immunology, New Delhi, India.
Akhil C
AC
Banerjea
Department of Endocrinology, Dr. ALM PG Institute of Basic Medical Sciences, University of Madras, Chennai 600 013, India.
Dinesh Babu
DB
Somasundaram
Centre for Bioinformatics, School of Life Sciences, Pondicherry University, Puducherry 605 014, India.
Mohane Selvaraj
MS
Coumar
Department of Biochemistry and Molecular Biology, School of Life Sciences, Pondicherry University, Puducherry 605 014, India.
Latha
L
Periyasamy
Department of Biochemistry and Molecular Biology, School of Life Sciences, Pondicherry University, Puducherry 605 014, India; Department of Biotechnology, University of Madras, Guindy Campus, Chennai, Tamilnadu 600025, India. Electronic address: ruks2k2@yahoo.co.in.
Rukkumani
R
Rajagopalan
D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D003198:Computer Simulation; D003474:Curcumin / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D062105:Molecular Docking Simulation; D016328:NF-kappa B / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000517:prevention & control; D009362:Neoplasm Metastasis / Q000517:prevention & control; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects
D016588:Anticarcinogenic Agents; C580697:BDMC-A; D016328:NF-kappa B; D003474:Curcumin
BDMC-A; Curcumin; MCF-7; Metastasis; NF-κB docking; Western blotting