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Improved synergistic anticancer efficacy of quercetin in combination with PI-103, rottlerin, and G0 6983 against MCF-7 and RAW 264.7 cells

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Abstract

Flavonoids have been chronicles of the history of a long way journey in the cure of physiological or pathophysiological conditions in various diseases including cancer. Our previous findings suggest the extensive mechanism of quercetin (QUE) mediated regression of cell survival, cell proliferation, oxidative stress, inflammation, and angiogenesis via modulating PI3K and PKC signaling in lymphoma as well as hepatocellular carcinoma. PI3K-PKC pathway is a key monitor of mammalian cells regulated by its different isoenzymes, which may exert similar or opposite cellular effects by differential coupling of signaling pathways. Put forward the invention of selective inhibitors against various isoenzymes is beneficial to reduce the burden of inclusive deleterious effects of drug for normal physiological process. Therefore, we hypothesized the improved anticancer efficacy of QUE in combination with isoenzyme inhibitors—rottlerin (ROT-PKCδ inhibitor), G0 6983 (PKCα inhibitor), and PI-103 (p110α-class I PI3K inhibitor) in MCF-7 and RAW 264.7 cells. QUE significantly improves the cytotoxicity of ROT + G0 6983 ranged 30–55% and PI-103 ranged 24–63% after 24–48 h against MCF-7 cells. Additionally in the presence of QUE, the improved cytotoxicity of ROT + G0 6983 is observed to range 69–75% and PI-103 ranged 45–88% after 24–48 h in RAW 264.7 cells. This increment in cell deaths are positively correlated with enhanced morphological alteration observed in MCF-7 cells. Further, QUE significantly increases the attenuation of PKCα level approximately by 50% in combination with PI-103. Overall results of the current study suggested that QUE improves the synergistic anticancer efficacy in combination with PI-103, ROT, and G0 6983 in MCF-7 and RAW 264.7 cells.

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Acknowledgements

MV is thankful to UGC-CAS program to Department of Zoology for infrastructural facilities.

Funding

This research was supported by University Grants Commission (UGC), India (Project No. F 40-209/2011 (SR) dated June 29, 2011) and CSIR, India, for JRF & SRF (CSIR Award No. File No. 09/013(0338)/2010-EMR-I).

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  1. Biochemistry & Molecular Biology Laboratory, Centre for Advanced Study in Zoology, Institute of Science, Banaras Hindu University, Varanasi, 221005, India

    Akhilendra Kumar Maurya & Manjula Vinayak

  2. Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA

    Akhilendra Kumar Maurya

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  1. Akhilendra Kumar Maurya
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  2. Manjula Vinayak
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Correspondence to Manjula Vinayak.

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Maurya, A.K., Vinayak, M. Improved synergistic anticancer efficacy of quercetin in combination with PI-103, rottlerin, and G0 6983 against MCF-7 and RAW 264.7 cells. In Vitro Cell.Dev.Biol.-Animal 55, 36–44 (2019). https://doi.org/10.1007/s11626-018-0309-8

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