Crosstalk from survival to necrotic death coexists in DU-145 cells by curcumin treatment.
Curcumin as an anticancer agent was investigated in regards to its ability to regulate the switching of cancer cells from survival to necrotic cell death. At higher concentrations, curcumin induced ROS production leading to JNK and p38 phosphorylation in DU-145 prostate cancer cells. Of the MAP kinases, ERK or p38/JNK were phosphorylated earlier during curcumin treatment, and were responsible for curcumin-induced cell survival at early time of treatment with the help of phosphorylated Akt, while significant amounts of ROS production in later periods stimulated cell death with caspase degradation. In addition to autophagic signaling, necrosis was dominant with little apoptotic cell death. Caspase activation was completely prohibited by procaspase degradation, which contributed to curcumin-induced early necrosis. At the later incubation period (24h), cytotoxicity caused by curcumin peaked, at which time survival or proliferation signals, such as phosphorylated Akt and phosphorylated ERK, was almost completely diminished. Curcumin-induced ROS were shown to function, biphasically depending on the incubation period; facilitating survival, in the earlier incubation period, and necrotic death in the later. Based on all of these results, we concluded that curcumin contributes to a complex signaling network, affecting cell survival and necrotic cell death, which in turn could inhibit apoptotic cell death.
Institute for Cancer Research, College of Medicine, Yonsei University, Seoul, Republic of Korea.
Dongxu
D
Kang
Wungki
W
Park
Seungha
S
Lee
Joo-Hang
JH
Kim
Jae J
JJ
Song
D000970:Antineoplastic Agents / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000633:toxicity*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D009336:Necrosis / Q000378:metabolism; D010766:Phosphorylation; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
D000970:Antineoplastic Agents; D017382:Reactive Oxygen Species; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D020169:Caspases; D003474:Curcumin