US EPA

4854443 

Journal Article 

Vanadium quercetin complex attenuates mammary cancer by regulating the P53, Akt/mTOR pathway and downregulates cellular proliferation correlated with increased apoptotic events 

Roy, S; Banerjee, S; Chakraborty, T 

2018 

Yes 

BioMetals
ISSN: 0966-0844
EISSN: 1572-8773 

SPRINGER 

DORDRECHT 

31 

4 

647-671 

English 

29855745 

10.1007/s10534-018-0117-3 

WOS:000440104700017 

https://www.proquest.com/docview/2049557314?accountid=171501&bdid=13857&_bd=At3BSGOep%2FeoLk6WTyLc%2Fc6SbJs%3D
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Flavonoid metal ion complexes have been deliberated in recent years and are considered as a new class of medicinal agents with enhanced therapeutic activity and low toxicity. Our study deals with chemotherapeutic effects of vanadium, when coordinated with the flavonoid quercetin on a defined model of chemically induced rat mammary carcinogenesis in vivo and on human breast cancer cell line MCF-7 in vitro. The characterization of the complex was achieved through UV-Visible, IR, and Mass spectra and antioxidant activity was assessed by DPPH, FRAP and ABTS methods. In vitro studies established that the complex upregulated the expressions of p53, Caspase 3 and 9, whereas down regulating Akt, mTOR and VEGF expressions and also induced apoptosis and DNA fragmentation in a dose dependent manner. Acute and Sub-acute toxicity was performed to determine safe doses. 7,12-Dimethylbenz(α)anthracene (0.5 mg/100 g body weight) was used for induction of breast cancer in female Sprague-Dawley rats via single tail vein injection. The histopathological analysis after 24 weeks of carcinogenesis study depicted substantial repair of hyperplastic lesions. TUNEL assay showed an increase in apoptotic index (0.14 ± 0.03; 0.15 ± 0.01) in vanadium-quercetin treated groups as compared to the carcinogen control (0.02 ± 0.01) along with upregulation of Bcl-2 and downregulation of Bax and p53. Immunohistochemical analysis also exhibited decrease in cell proliferation in the vanadium-quercetin treated groups (11.3 ± 0.12; 11.8 ± 0.10). Thus, results from both in vivo and in vitro studies revealed that vanadium-quercetin complex could be a potential candidate for development of approved drug for breast cancer in the near future.