Curcumin induces apoptosis in p53-null Hep3B cells through a TAp73/DNp73-dependent pathway.
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 (Hep3B(TAp73/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 Hep3B(TAp73/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.
Department of Pharmacology, Weifang Medical University, Weifang, 261053, China. jinrongwangwf@126.com.
Jinhong
J
Wang
Department of Nuclear Medicine, Weifang Medical University, Weifang, 261053, China.
Hai
H
Xie
Department of Pharmacology, Weifang Medical University, Weifang, 261053, China.
Feng
F
Gao
Department of Pharmacology, Weifang Medical University, Weifang, 261053, China.
Tingkun
T
Zhao
Department of Pharmacology, Weifang Medical University, Weifang, 261053, China.
Hongming
H
Yang
Department of Pharmacology, Weifang Medical University, Weifang, 261053, China.
Bai
B
Kang
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology*; D004249:DNA Damage; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D015398:Signal Transduction; D015533:Transcriptional Activation; D000072160:Tumor Protein p73 / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D000972:Antineoplastic Agents, Phytogenic; C495901:TP53 protein, human; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D003474:Curcumin
Apoptosis; Curcumin; DNA damage; DNp73; TAp73