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

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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.

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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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Authors and Affiliations

  1. Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Keio University, 1-5-30, Shibakoen, Minato-ku, Tokyo, 105-8512, Japan

    Takeshi Akiyoshi & Kenji Matsuyama

  2. School of Pharmaceutical Sciences, Mukogawa Women’s University, 11-68, Kyuban-cho, Koshien, Nishinomiya, Hyogo, 663-8179, Japan

    Sumio Matzno, Mika Sakai & Noboru Okamura

  3. The Joint Center of Industry and Mukogawa Women’s University for Developing Receptor Targeting Anticancer Agents, 11-68, Kyuban-cho, Koshien, Nishinomiya, Hyogo, 663-8179, Japan

    Sumio Matzno & Noboru Okamura

Authors
  1. Takeshi Akiyoshi
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  2. Sumio Matzno
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  3. Mika Sakai
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Correspondence to Sumio Matzno.

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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

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