title: Induction of apoptosis by 4-(3-(tert-butylamino)imidazo[1,2-α]pyridine-2-yl) benzoic acid in breast cancer cells via upregulation of PTEN.
abstract: We have previously reported that 4-(3-(tert-butylamino)imidazo[1,2-α]pyridine-2-yl)benzoic acid, a bicyclic N-fused aminoimidazoles derivative (BNFA-D), possesses anticancer potentiality against breast and kidney cancer cells with minimal toxicities to corresponding normal cells. Here, we explored the mechanism of action of BNFA-D in breast cancer cells using multiple cell-based assays such as MTT, DAPI, FACS, Western blot, and immunoprecipitation. BNFA-D caused apoptosis by upregulating PTEN leading to inhibition of Wnt/TCF signaling cascade and arresting S phase in breast cancer cells. Expression levels of β-catenin, cyclin D1, C-MYC, and phospho-AKT (Ser(473)) decreased with simultaneous increase in the levels of GSK3β, CK1, and PTEN in BNFA-D-treated MCF-7 cells. Interestingly, silencing of PTEN in breast cancer cells reversed the phenomenon of Wnt/TCF signaling cascade inhibition after BNFA-D treatment.
authors: Cancer Biology Division, KIIT School of Biotechnology, KIIT University, Bhubaneswar, Odisha, India.
authors: Sumit
authors: S
authors: Siddharth
authors: Purusottam
authors: P
authors: Mohapatra
authors: Ranjan
authors: R
authors: Preet
authors: Dipon
authors: D
authors: Das
authors: Shakti Ranjan
authors: SR
authors: Satapathy
authors: Tathagata
authors: T
authors: Choudhuri
authors: Chanakya Nath
authors: CN
authors: Kundu
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001565:Benzoates / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000201:enzymology; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D005260:Female; D055785:Gene Knockdown Techniques; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D061986:MCF-7 Cells; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D051820:TCF Transcription Factors / Q000378:metabolism; D014162:Transfection; D015854:Up-Regulation / Q000187:drug effects; D060449:Wnt Signaling Pathway / Q000187:drug effects
chemical_list: D001565:Benzoates; D007093:Imidazoles; D011725:Pyridines; D051820:TCF Transcription Factors; D019869:Phosphatidylinositol 3-Kinases; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human