Abstract
C-Jun N-terminal kinase (JNK) represents a group of mitogen-activated protein kinases (MAPKs) involved in many cellular responses including apoptosis. We have previously reported that taxol, a microtubule-interfering therapeutic agent widely used against various cancers, induces caspase-independent but apoptotic inducing factor (AIF)-dependent apoptosis in human ovarian cancer cell line SKOV3 cells. In the present study, we add to this report a detailed analysis of the taxol-induced apoptotic mechanisms in SKOV3 cells, particularly focusing on JNK and p53. In line with the previous report, we found that taxol induced caspase-independent apoptosis with concurrent activation of JNK, phosphorylation of Bcl-2, Bax translocation to the mitochondria, and AIF release from the mitochondria. Restoration of p53 functionality into SKOV3 cells, which are p53-null cells, by transfection of wild-type p53, however, induced caspase-dependent apoptosis in response to taxol treatment as evidenced by increasing PARP cleavage and the emergence of processed, active caspase-3 and -7. More to the point, treatment with a JNK inhibitor SP600125 blocked taxol-induced apoptotic cell death in both parental SKOV3 cells (p53-deficient) and p53-transfectant cells. Collectively, the aforementioned findings lend support to the view that taxol-induced apoptotic cell death in SKOV3 cells is executed by different mechanisms depending on the presence of p53 but commonly mediated by ASK1-JNK and/or -p38 axes.
Highlights
Charactor of Jun N-terminal kinase (JNK) and P53 in Taxol-Induced Apoptotic Signaling in SKOV3 Human Ovarian Cancer Cell Proliferation
We have previously reported that taxol, a microtubule-interfering therapeutic agent widely used against various cancers, induces caspase-independent but apoptotic inducing factor (AIF)-dependent apoptosis in human ovarian cancer cell line SKOV3 cells
In line with the previous report, we found that taxol induced caspase-independent apoptosis with concurrent activation of JNK, phosphorylation of Bcl-2, Bax translocation to the mitochondria, and AIF release from the mitochondria
Summary
Received date: July 30,2017;Accepted date : August 20,2017; Published date: September 04,2017 Citation for this Article: Medo Al-Inany, Mostafa A , Charactor of JNK and P53 in Taxol-Induced Apoptotic Signaling in SKOV3 Human. We have previously reported that taxol, a microtubule-interfering therapeutic agent widely used against various cancers, induces caspase-independent but apoptotic inducing factor (AIF)-dependent apoptosis in human ovarian cancer cell line SKOV3 cells. We reported a caspase-independent but AIF-dependent apoptosis in association with taxol treatment in SKOV3 human ovarian cancer cells. Extending this finding, in this study, we have demonstrated that the phosphorylation of JNK is a key molecular event in the taxolinduced apoptotic signal transduction in SKOV3 cells. When p53 is restored into SKOV3 cells, the taxol-induced apoptotic signaling is shifted from a caspase-independent to a caspase-dependent signaling, raising an intriguing possibility of conferring on p53 a new role in the apoptotic cell death
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