Tolypothrix Dichloromethane Ethylacetate fraction (TDEF) inhibits cisplatin resistance H357 cell through PI3K/AKT/beta-catenin pathway

• Published in: American journal of cancer research Vol. 14; no. 3; pp. 1071 - 1086
• Main Authors: Heisnam, Rameshwari, Thoithoisana Devi, Soibam, Mohanty, Sibasish, Mukherjee, Pulok K, Rayala, Vvs Prasanna Kumari, Radhakrishnanand, Pullapanthula, Dash, Rupesh, Sharma, Nanaocha
• Format: Journal Article
• Language: English
• Published: United States e-Century Publishing Corporation 01.01.2024
• Subjects: Original; β-catenin; chemoresistance; H357cisR; p21; antibody array
• ISSN: 2156-6976; 2156-6976
• DOI: 10.62347/JTNQ4812

Chemoresistance is one of the major factors for treatment failure in OSCC. Reprogramming chemoresistance cells to undergo drug induced apoptotic cell death is a feasible approach to overcome drug resistance. Cyanobacteria is considered important sources of lead compounds for the development of drugs for treating cancer chemoresistance. This study deals with the role of Tolypothrix Dichloromethane Ethyl acetate fraction (TDEF) inducing apoptosis in cisplatin resistance H357 cell (H357cisR) and the underlying mechanisms sensitizing the chemoresistance. TDEF showing effective activity against H357cisR with IC -14.13±1.18 µg mL , inhibits proliferation and migration. Proteome apoptosis arrays were found to stimulate phosphorylation of p53, activation of proapoptotic proteins including BAX and cytochrome C (CYCS), caspase-3/9 (CASP3/9), suppression of anti-apoptotic proteins like Bcl2, survivin and increased expression of the cell cycle checkpoint protein p21, p27. TDEF induced apoptosis with cell death-transducing signals, that regulate the Matrix metalloproteinases (MMPs) by down-regulation of Bcl2 and up-regulation of Bax, triggering the cytochrome c release from mitochondria to cytosol thus triggered the activation of caspases-9 to activate downstream executioner caspase-3/7 required for apoptotic changes. The mechanistic pathway of apoptotic cell death in H357cisR was done through inhibiting β-catenin through GSK3β in turn activated by AKT. The phosphorylated β-catenin leads to proteasome degradation and unable to translocation to nucleus thereby activating c-Myc, survivin, Cyclin D and upregulate p21 expression which lead to cell cycle arrest in G /G phase.