Antiproliferative pharmacophore azo-hydrazone analogue BT-1F exerts death signalling pathway targeting STAT3 in solid tumour
| العنوان: | Antiproliferative pharmacophore azo-hydrazone analogue BT-1F exerts death signalling pathway targeting STAT3 in solid tumour |
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| المؤلفون: | Banumathi, Ankith, Sherapura, Vikas H, Malojirao, Zabiulla, B S, Sharath, Prabhu, Thirusangu, Riaz, Mahmood, N Suchetha, Kumari, Shrinath M, Baliga, Shaukath Ara, Khanum, B T, Prabhakar |
| المصدر: | Pharmacological Reports. 74:353-365 |
| بيانات النشر: | Springer Science and Business Media LLC, 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | STAT3 Transcription Factor, Pharmacology, Cell Line, Tumor, Hydrazones, Apoptosis, General Medicine, Janus Kinase 2, Tumor Suppressor Protein p53, Cell Proliferation, Signal Transduction |
| الوصف: | Anomalous activation of intra-cellular signalling cascades confers neoplastic properties on malignant cells. The JAK2/STAT3 proteins play a pivotal role in the pathogenesis of most of the solid malignancies. The over expression of STAT3 in these tumours results in an evasion of apoptosis and thereby pathogenesis. Hence, strategy to target STAT3 to regress tumour development is an emerging new concept. As an approach, anti-neoplastic drug, Azo-hydrozone analogue, BT-1F with potential anti-proliferative effect was evaluated to demonstrate its capacity to counteract STAT3 signal with mechanistic approach.Cell based screening for cytotoxicity was performed through MTT, LDH and Trypan blue. The BT-1F induced anti-clonogenic property by clonogenic assay. The apoptotic capacity was examined by crystal violet staining, flow cytometry, Annexin-FITC, DAPI and TUNEL assay. The altered signalling events were studied using immunoblot. The drug-induced anti-tumour effect was evaluated in an in-vivo solid tumour model and molecular interaction was further validated by in-silico studies.The BT-1F exerts chemo-sensitivity specifically against EAC and A549 cells without altering its normal counterpart. The anti-proliferative/anti-clonogenic effect was due to the induction of apoptosis through inhibition of STAT3Systemic validation of STAT3 target drug, BT-1F in in-vitro, in-silico and in-vivo models has promising strategy for solid cancer treatment. |
| تدمد: | 2299-5684 1734-1140 |
| DOI: | 10.1007/s43440-021-00345-w |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7865f20c48a11fbce125fbfc6ba2ea7f https://doi.org/10.1007/s43440-021-00345-w |
| Rights: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....7865f20c48a11fbce125fbfc6ba2ea7f |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 22995684 17341140 |
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| DOI: | 10.1007/s43440-021-00345-w |