Volume 65, Number 1, 143-150, DOI: 10.1007/s00280-009-1016-7

The potential of vitamin K3 as an anticancer agent against breast cancer that acts via the mitochondria-related apoptotic pathway

Takeshi Akiyoshi, Sumio Matzno, Mika Sakai, Noboru Okamura and Kenji Matsuyama

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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.

Keywords  Vitamin K3  - Breast cancer - ROS - Mitochondrial dysfunction

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