Vitamin K4 induces tumor cytotoxicity in human prostate carcinoma PC-3 cells via the mitochondria-related apoptotic pathway
Vitamin K4 (VK4) is a synthetic hydrophilic menadione compound, which is clinically used as hemostasis medicine. It has been reported that several vitamin Ks had inhibitory effects on various cancer cells. However, there is no report about VK4 s anticancer activity. The goal of this study was to inv...
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Published in | Pharmazie Vol. 68; no. 6; pp. 442 - 448 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Germany
Govi-Verlag
01.06.2013
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Abstract | Vitamin K4 (VK4) is a synthetic hydrophilic menadione compound, which is clinically used as hemostasis medicine. It has been reported that several vitamin Ks had inhibitory effects on various cancer cells. However, there is no report about VK4 s anticancer activity. The goal of this
study was to investigate the inhibitory effect of VK4 on human prostate PC-3 cells and the mechanisms involved. We found that VK4 dose-dependently inhibited cell proliferation in PC-3 cells with an IC50 value of about 20.94 μM. Hoechst 33258 Staining results showed that VK4 caused
DNA fragmentation in PC-3 cells. PI staining results indicated that VK4-induced PC-3 cell cycle arrest at the S phase. Further mechanistic studies revealed that VK4-mediated induction of apoptosis in PC-3 cell is associated with disruption of mitochondrial membrane potential, down-regulation
of Bcl-2, and up-regulation of Bax, release of cytochrome c from mitochondria, and activation of caspase-3 and PARP. Thus, VK4 might be useful in prostate cancer chemotherapy. |
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AbstractList | Vitamin K4 (VK4) is a synthetic hydrophilic menadione compound, which is clinically used as hemostasis medicine. It has been reported that several vitamin Ks had inhibitory effects on various cancer cells. However, there is no report about VK4s anticancer activity. The goal of this study was to investigate the inhibitory effect of VK4 on human prostate PC-3 cells and the mechanisms involved. We found that VK4 dose-dependently inhibited cell proliferation in PC-3 cells with an IC50 value of about 20.94 microM. Hoechst 33258 Staining results showed that VK4 caused DNA fragmentation in PC-3 cells. PI staining results indicated that VK4-induced PC-3 cell cycle arrest at the S phase. Further mechanistic studies revealed that VK4-mediated induction of apoptosis in PC-3 cell is associated with disruption of mitochondrial membrane potential, down-regulation of Bcl-2, and up-regulation of Bax, release of cytochrome c from mitochondria, and activation of caspase-3 and PARR Thus, VK4 might be useful in prostate cancer chemotherapy. Vitamin K4 (VK4) is a synthetic hydrophilic menadione compound, which is clinically used as hemostasis medicine. It has been reported that several vitamin Ks had inhibitory effects on various cancer cells. However, there is no report about VK4 s anticancer activity. The goal of this study was to investigate the inhibitory effect of VK4 on human prostate PC-3 cells and the mechanisms involved. We found that VK4 dose-dependently inhibited cell proliferation in PC-3 cells with an IC50 value of about 20.94 μM. Hoechst 33258 Staining results showed that VK4 caused DNA fragmentation in PC-3 cells. PI staining results indicated that VK4-induced PC-3 cell cycle arrest at the S phase. Further mechanistic studies revealed that VK4-mediated induction of apoptosis in PC-3 cell is associated with disruption of mitochondrial membrane potential, down-regulation of Bcl-2, and up-regulation of Bax, release of cytochrome c from mitochondria, and activation of caspase-3 and PARP. Thus, VK4 might be useful in prostate cancer chemotherapy. |
Author | Yang, Hong Yang, Jingbo Zhou, Yongfeng Yu, Bo Yang, Chunhui Meng, Fanmin Khan, Muhammad Jiang, Yu |
Author_xml | – sequence: 1 givenname: Yu surname: Jiang fullname: Jiang, Yu – sequence: 2 givenname: Jingbo surname: Yang fullname: Yang, Jingbo – sequence: 3 givenname: Chunhui surname: Yang fullname: Yang, Chunhui – sequence: 4 givenname: Fanmin surname: Meng fullname: Meng, Fanmin – sequence: 5 givenname: Yongfeng surname: Zhou fullname: Zhou, Yongfeng – sequence: 6 givenname: Bo surname: Yu fullname: Yu, Bo – sequence: 7 givenname: Muhammad surname: Khan fullname: Khan, Muhammad – sequence: 8 givenname: Hong surname: Yang fullname: Yang, Hong |
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SubjectTerms | Animals Antineoplastic Agents Apoptosis - drug effects Blotting, Western Caspase 3 - physiology Cell Cycle - drug effects Cell Line, Tumor Cell Proliferation - drug effects Cell Survival - drug effects DNA Fragmentation Flow Cytometry Humans Indicators and Reagents Male Membrane Potential, Mitochondrial - drug effects Mice Mitochondria - drug effects Prostatic Neoplasms - drug therapy Prostatic Neoplasms - pathology Reactive Oxygen Species - metabolism Spleen - cytology Spleen - drug effects Tetrazolium Salts Thiazoles Vitamin K 3 - analogs & derivatives Vitamin K 3 - pharmacology |
Title | Vitamin K4 induces tumor cytotoxicity in human prostate carcinoma PC-3 cells via the mitochondria-related apoptotic pathway |
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