Vitamins K1 and K2 potentiate hyperthermia by down-regulating Hsp72 expression in vitro and in vivo

Shuji Shimohara, Toru Murakami, Mari Morikawa, Junko Matsuo, Shin Ichi Nagayama, Tsuyoshi Shuto, Mary Ann Suico, Tsukasa Okiyoneda, Isao Yamatsu, Toru Mizushima, Tatsuya Shimasaki, Hirofumi Kai

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5 Citations (Scopus)

Abstract

Hyperthermia is used to treat various malignancies, including esophageal, stomach and rectal cancer. Since hyperthermia alone has produced limited results, much attention has been focused on combining hyperthermia with chemotherapy and on searching for substances able to sensitize tumor cells to hyperthermia-induced damage. Here, we show that vitamins K1 and K2 (VK1, VK2) inhibited the expression of heat-shock protein 72 (Hsp72) but did not affect the constitutive expression of Hsc70 or calnexin in vitro and in vivo. VK, and VK2 sensitized A549 cells to heat-shock induced cell death, while the compounds alone had no effect on cell viability. The suppression of Hsp72 was apparently at the protein level because the mRNA expression of Hsp72 was unchanged. Moreover, the chaperone activity of Hsp72 was compromised after heat-shock when cells were pre-treated with VK 2. The effect of VK2 on Hsp72 suppression, however, was also observed in normal mouse tissue after the mice were subjected to whole-body hyperthermia. To eliminate this side effect, local hyperthermia was performed on tumors in mice. The pre-treatment with VK2 potentiated the effect of local hyperthermia on tumor growth suppression. The findings here that VK1 and VK2 inhibit heat-shock-induced Hsp72 suggest their possible use as an adjuvant for hyperthermia in cancer therapy.

Original languageEnglish
Pages (from-to)1527-1533
Number of pages7
JournalInternational journal of oncology
Volume27
Issue number6
Publication statusPublished - 2005 Dec 1

Keywords

  • Heat shock
  • Hsp72
  • Hyperthermia
  • Tumor cells
  • Vitamin K

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Shimohara, S., Murakami, T., Morikawa, M., Matsuo, J., Nagayama, S. I., Shuto, T., Suico, M. A., Okiyoneda, T., Yamatsu, I., Mizushima, T., Shimasaki, T., & Kai, H. (2005). Vitamins K1 and K2 potentiate hyperthermia by down-regulating Hsp72 expression in vitro and in vivo. International journal of oncology, 27(6), 1527-1533.