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The Mechanism of PTS2 Inducing HeLa Cell Apoptosis

Author: ChenHui
Tutor: YinZhiMin
School: Nanjing Normal University
Course: Biochemistry and Molecular Biology
Keywords: PTS2 Apoptosis ERK1 / 2 p38
CLC: R73-3
Type: Master's thesis
Year: 2007
Downloads: 89
Quote: 0
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Abstract


The bis pyrithione (2,2 '- bipyridine N-oxide disulfide , Dipyrithione ) is one of the many derivatives of the hydroxypyridine thiones compounds having effective antibacterial and antifungal activity . PTS2 clinically as antibacterial agents , insecticides, and antifungal agents has been widely applied. The study found that the PTS2 induced apoptosis in HeLa cells , and to explore the molecular mechanisms . Clarify PTS2 proapoptotic role , in PTS2 role in HeLa cells , Hoechst 33258 and DAPI staining , fluorescence microscopy observation chromatin morphology ; MTT assay cell viability ; application of flow cytometry to detect apoptosis rate . The experimental results show that the PTS2 can induce apoptosis in HeLa cells , was dose and time dependent Yang . Cytochrome C play an important role in the mitochondrial pathway of apoptosis . Caspase-3 is a of apoptosis downstream signaling pathways important protease , cytochrome C release from mitochondria , activation of caspase -3 . Confirmed Cytochrome C and Caspase-3 in PTS2 - induced apoptosis in HeLa cells , the Western blot test results show the PTS2 can lead to cytochrome C. Release from mitochondria , Caspase-3 is activated , its downstream substrate PARP do occur Cut and PTS2 presents the time-and dose -dependent . Reported that the MAPK signaling pathway is involved in the role of chemotherapeutic drugs on tumor cells , we analyzed the JNK1 / 2, ERK1 / 2 and p38 induced apoptosis in HeLa role in PTS2 results show that the ERK1 / 2 and p38 was significantly activated JNK1 / 2 activation is not obvious . Application of p38 inhibitor SB203580 reduced apoptosis in HeLa cells and inhibit the release of cytochrome C and activation of caspase -3 , and PARP shear . Application of ERK1 / 2 inhibitor PD98059 caused the opposite effect, reveal the play the anti-tumor effect in the process of in the PTS2 -induced apoptosis in HeLa cells . Our study is the first confirmed PTS2 has anti- tumor effect , cytochrome C, Caspase-3 and PARP role involved in the the PTS2 induction of apoptosis in HeLa cells , ERK1 / 2 and p38 play the opposite role in this process .

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