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PQ1, a quinoline derivative, induces apoptosis in T47D breast cancer cells through activation of caspase-8 and caspase-9

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Abstract

Apoptosis, a programmed cell death, is an important control mechanism of cell homeostasis. Deficiency in apoptosis is one of the key features of cancer cells, allowing cells to escape from death. Activation of apoptotic signaling pathway has been a target of anti-cancer drugs in an induction of cytotoxicity. PQ1, 6-methoxy-8-[(3-aminopropyl)amino]-4-methyl-5-(3-trifluoromethylphenyloxy)quinoline, has been reported to decrease the viability of cancer cells and attenuate xenograft tumor growth. However, the mechanism of the anti-cancer effect is still unclear. To evaluate whether the cytotoxicity of PQ1 is related to induction of apoptosis, the effect of PQ1 on apoptotic pathways was investigated in T47D breast cancer cells. PQ1-treated cells had an elevation of cleaved caspase-3 compared to controls. Studies of intrinsic apoptotic pathway showed that PQ1 can activate the intrinsic checkpoint protein caspase-9, enhance the level of pro-apoptotic protein Bax, and release cytochrome c from mitochondria to cytosol; however, PQ1 has no effect on the level of anti-apoptotic protein Bcl-2. Further studies also demonstrated that PQ1 can activate the key extrinsic player, caspase-8. Pre-treatment of T47D cells with caspase-8 or caspase-9 inhibitor suppressed the cell death induced by PQ1, while pre-treatment with caspase-3 inhibitor completely counteracted the effect of PQ1 on cell viability. This report provides evidence that PQ1 induces cytotoxicity via activation of both caspase-8 and caspase-9 in T47D breast cancer cells.

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Acknowledgments

We gratefully acknowledge the financial support from the National Institute of Health, P20RR016475 and R15CA152922.

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Biochemistry, Kansas State University, K244 Mosier Hall, 1800 Denison Avenue, Manhattan, KS, 66506, USA

    Ying Ding

  2. Department of Diagnostic Medicine/Pathobiology, Kansas State University, K244 Mosier Hall, 1800 Denison Avenue, Manhattan, KS, 66506, USA

    Thu Annelise Nguyen

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  1. Ying Ding
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  2. Thu Annelise Nguyen
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Correspondence to Thu Annelise Nguyen.

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Ding, Y., Nguyen, T.A. PQ1, a quinoline derivative, induces apoptosis in T47D breast cancer cells through activation of caspase-8 and caspase-9. Apoptosis 18, 1071–1082 (2013). https://doi.org/10.1007/s10495-013-0855-1

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  • DOI: https://doi.org/10.1007/s10495-013-0855-1

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