Search Our Scientific Publications & Authors

Publications
find publications by category +
Translate page:

Antiproliferative pharmacophore azo-hydrazone analogue BT-1F exerts death signalling pathway targeting STAT3 in solid tumour.

Authors:
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

Pharmacol Rep 2022 Apr 10;74(2):353-365. Epub 2022 Jan 10.

Molecular Biomedicine Laboratory, Postgraduate Department of Studies and Research in Biotechnology, Sahyadri Science College, Kuvempu University, Shivamogga, Karnataka, 577203, India.

Background: 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.

Methods: 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.

Results: 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 STAT3 signal. Eventually downstream signalling proteins p53, Bax, Bad and Bcl-xL were significantly altered. Further in-vivo experimental results validated  in-vitro findings. The computational approaches assures the BT-1F efficiency in binding with STAT3.

Conclusion: Systemic validation of STAT3 target drug, BT-1F in in-vitro, in-silico and in-vivo models has promising strategy for solid cancer treatment.

Download full-text PDF

 Source
http://dx.doi.org/10.1007/s43440-021-00345-wDOI Listing
April 2022

Publication Analysis

Top Keywords

stat3 signal
8
analogue bt-1f
8
solid tumour
8
bt-1f exerts
8
bt-1f
6
stat3
6
cancer treatment
4
altered signalling
4
staining flow
4
flow cytometry
4
cytometry annexin-fitc
4
annexin-fitc dapi
4
dapi tunel
4
tunel assay
4
assay altered
4
studied immunoblot
4
signalling events
4
events studied
4
crystal violet
4
immunoblot drug-induced
4

Keyword Occurance

Similar Publications

HOXA5 inhibits adipocytes proliferation through transcriptional regulation of Ccne1 and blocking JAK2/STAT3 signaling pathway in mice.

Authors:
Miao Pan Qian Sun Chaowei Li Ruiqing Tai Xin'e Shi Chao Sun

Biochem Cell Biol 2022 May 27. Epub 2022 May 27.

Northwest A&F University, 12469, Yangling, Shaanxi, China;

The highly regulated proliferation of adipocytes plays a momentous role in fat development and obesity. Hoxa5 is an important member of Hox family, its encoded protein is an important transcription factor related to development. And its differential expression in different adipose tissues seems to indicate that Hoxa5 may be involved in the regulation of adipocyte proliferation. Read More

View Article and Full-Text PDF
May 2022
Similar Publications

Curcumin inhibits the cancer‑associated fibroblast‑derived chemoresistance of gastric cancer through the suppression of the JAK/STAT3 signaling pathway.

Authors:
In-Hye Ham Lei Wang Dagyeong Lee Jongsu Woo Tae Hoon Kim Hye Young Jeong Hye Jeong Oh Kyeong Sook Choi Tae-Min Kim Hoon Hur

Int J Oncol 2022 Jul 27;61(1). Epub 2022 May 27.

Department of Surgery, Ajou University School of Medicine, Suwon, Gyeonggi‑do 16499, Republic of Korea.

The present study aimed to investigate whether the Janus‑activated kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) signaling pathway is a critical mechanism underlying the cancer‑associated fibroblast (CAF)‑induced chemoresistance of gastric cancer (GC). In addition, the present study tried to suggest a natural product to compromise the effects of CAF on the chemoresistance of GC. The results of cell proliferation assay revealed that the conditioned medium (CM) collected from CAFs further increased resistance to 5‑fluorouracil (5‑FU) in GC cell lines. Read More

View Article and Full-Text PDF
July 2022
Similar Publications

Explore the Effect of Asthma Regulating HIF-1 Pathway on Sperm Quality Based on Rat Model.

Authors:
Junlong Feng Yuan Tang Zhen Yang Binghao Bao Yichen Liu Sheng Deng Haisong Li Jiangbin Li Jisheng Wang

Biomed Res Int 2022 17;2022:4194685. Epub 2022 May 17.

Department of Andrology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China.

This study is to verify the effect of asthma on sperm quality and explore its potential underlying mechanism. We randomly categorized the Sprague-Dawley (SD) rats into control (Group C) and asthma model (Group M) groups. Rats in the asthma model group were induced allergic asthma by intraperitoneal injection of ovalbumin solution. Read More

View Article and Full-Text PDF
May 2022
Similar Publications

PROPHYLACTIC EFFECT OF NITRIC OXIDE DONORS ON RAT MODELS OF EGFR INHIBITORS-INDUCED CUTANEOUS TOXICITIES.

Authors:
Xinran Xie Leying Chen Xin Liu Zhaoyu Wu Dazhao Lv Yurui Ma Jie Luo Shiyi Zhang

J Invest Dermatol 2022 May 23. Epub 2022 May 23.

School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, People's Republic of China. Electronic address:

Epidermal growth factor receptor inhibitors (EGFRIs) have been established as first-line standard-of-care therapies for non-small cell lung cancer (NSCLC) but are frequently accompanied by adverse dermatological effects, in particular, acneiform rash. There is no effective clinical intervention, partially because of its poorly understood etiology. Here, we show that inhibition of EGFR initiated keratinocyte HaCaT cell cycle arrest and apoptosis, which fueled a robust secondary inflammatory response. Read More

View Article and Full-Text PDF
May 2022
Similar Publications

From a Computational Perspective: Elucidating the Neurotherapeutic and Inhibitory properties of LRRK2 Kinase Domain by a benzothiazole-based compound.

Authors:
Temitayo I Subair Opeyemi S Soremekun Fisayo A Olotu Mahmoud E S Soliman

Curr Pharm Biotechnol 2022 May 23. Epub 2022 May 23.

Molecular Bio-computation and Drug Design Laboratory, School of Health Sciences, University of KwaZulu-Natal, Westville Campus, Durban 4001, South Africa.

Background: Parkinson's disease (PD) is one of the most prominent neurodegenerative diseases hence the continual search for viable and effective treatment options. The pathogeny of PD is driven by many key proteins among which is the recently identified Leucine-rich repeated kinase 2 (LRRK2). Going forward, the onus lies on identifying small-molecule inhibitors that can halt its pathogenic involvement, and, importantly, possess the capacity to cross the blood-brain barrier (BBB). Read More

View Article and Full-Text PDF
May 2022
Similar Publications
}