Abstract
Purpose
We tried to clarify the cytotoxic mechanism of VK3 using the breast cancer cell line MCF-7.
Methods
Cytotoxicity was measured via intracellular esterase activity. DNA fragmentation was assessed by agarose gel electrophoresis. JC-1 staining was applied to measure mitochondrial dysfunction. Caspase activation and reactive oxidative species (ROS) generation were also measured.
Results
VK3 exhibited cytotoxicity that caused DNA fragmentation in MCF-7 cells with an IC50 of 14.2 μM. JC-1 staining revealed that VK3 caused mitochondrial dysfunction including a disappearance of mitochondrial membrane potential. Additional investigation showed that the mitochondrial damage was induced by the generation of ROS and the subsequent activation of caspase-7 and -9.
Conclusions
Our findings demonstrate that VK3-induced apoptosis is selectively initiated by the mitochondria-related pathway and might be useful in breast cancer chemotherapy.
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Abbreviations
- VK3 :
-
Vitamin K3
- ROS:
-
Reactive oxidative species
- ER:
-
Endoplasmic reticulum
- HMEpC:
-
Human mammary epithelial cells
- DCFH-DA:
-
2′:7′-Dichlorofluorescein diacetate
- FMK:
-
Fluoromethylketone
- AMC:
-
7-Amino-4-methylcoumarin
- DMSO:
-
Dimethyl sulfoxide
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Acknowledgments
This work was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan.
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Akiyoshi, T., Matzno, S., Sakai, M. et al. The potential of vitamin K3 as an anticancer agent against breast cancer that acts via the mitochondria-related apoptotic pathway. Cancer Chemother Pharmacol 65, 143–150 (2009). https://doi.org/10.1007/s00280-009-1016-7
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DOI: https://doi.org/10.1007/s00280-009-1016-7