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Curcumin induces apoptosis in p53-null Hep3B cells through a TAp73/DNp73-dependent pathway

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Tumor Biology

Abstract

Curcumin has anticancer functions in various tumors. It has been shown to induce apoptosis through p53-dependent pathways. p73 gene is a member of the p53 family which encodes both a tumor suppressor (transactivation-competent p73 (TAp73)) and a putative oncogene (dominant-negative p73 (DNp73)); the former shares similarity with the tumor suppressor p53, and the latter behaves as dominant-negative proteins that interfere with the activity of TAp73. To understand the p73-dependent mechanisms that are engaged during curcumin-induced apoptosis, we established a p73 overexpression cell models using p53-deficient Hep3B cells (Hep3BTAp73/DNp73). Our results demonstrated that curcumin at concentrations of 40 and 80 μM induced DNA damage, increased TAp73/DNp73 ratio, and also led to apoptosis in the Hep3BTAp73/DNp73 cells. The apoptotic cell death was concurrent with the loss of mitochondrial membrane potential; release of cytochrome c from mitochondria; and the cleavage of caspase 9, caspase 3, and poly(ADP-ribose) polymerase (PARP). These results demonstrated a p73-dependent mechanism for curcumin-induced apoptosis that involves the mitochondria-mediated pathway.

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Abbreviations

BAX:

BCL-2-associated X protein

BCL-2:

B-cell leukemia/lymphoma 2

MMP:

Mitochondrial membrane potential

TAp73:

Transactivation-competent p73

DNp73:

Dominant-negative p73

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Acknowledgments

This work was supported by grants from National Natural Science Foundation of China (No. 82042282) and grants from Natural Science Foundation of Shandong Province (No. ZR2014HL106).

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Authors and Affiliations

  1. Department of Pharmacology, Weifang Medical University, Weifang, 261053, China

    Jinhong Wang, Feng Gao, Tingkun Zhao, Hongming Yang & Bai Kang

  2. Department of Nuclear Medicine, Weifang Medical University, Weifang, 261053, China

    Hai Xie

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  1. Jinhong Wang
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Correspondence to Jinhong Wang.

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Wang, J., Xie, H., Gao, F. et al. Curcumin induces apoptosis in p53-null Hep3B cells through a TAp73/DNp73-dependent pathway. Tumor Biol. 37, 4203–4212 (2016). https://doi.org/10.1007/s13277-015-4029-3

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