Oridonin induces apoptosis in human oral cancer cells via phosphorylation of histone H2<scp>AX</scp>

  • In‐Hyoung Yang
    Department of Oral Pathology School of Dentistry Institute of Oral Bioscience Chonbuk National University Jeonju Republic of Korea
  • Ji‐Ae Shin
    Department of Oral Pathology School of Dentistry and Dental Research Institute Seoul National University Seoul Republic of Korea
  • Kyung‐Eun Lee
    Department of Oral Medicine School of Dentistry Chonbuk National University Jeonju Republic of Korea
  • Junghyun Kim
    Department of Oral Pathology School of Dentistry Institute of Oral Bioscience Chonbuk National University Jeonju Republic of Korea
  • Nam‐Pyo Cho
    Department of Oral Pathology School of Dentistry Institute of Oral Bioscience Chonbuk National University Jeonju Republic of Korea
  • Sung‐Dae Cho
    Department of Oral Pathology School of Dentistry and Dental Research Institute Seoul National University Seoul Republic of Korea

抄録

<jats:p>Oridonin, a natural diterpenoid purified from <jats:italic>Rabdosia rubescens</jats:italic>, has displayed beneficial biological activities, including anti‐proliferation and anti‐angiogenesis effects, in various types of cancers. However, the anti‐cancer potential of oridonin and its mechanism in oral cancer have never previously been studied. In this study, we assessed the role of oridonin as an inducer of apoptosis in <jats:styled-content style="fixed-case">HSC</jats:styled-content>‐3 and <jats:styled-content style="fixed-case">HSC</jats:styled-content>‐4 human oral cancer cells. Our results showed that oridonin reduces the viability of human oral cancer cells and significantly increases the expression of <jats:italic>γ</jats:italic>H2<jats:styled-content style="fixed-case">AX</jats:styled-content>, a well‐known marker of <jats:styled-content style="fixed-case">DNA</jats:styled-content> damage. 4′,6‐Diamidino‐2‐phenylindole (<jats:styled-content style="fixed-case">DAPI</jats:styled-content>) staining and western blotting showed that oridonin causes nuclear condensation and fragmentation, and induces cleavage of poly(<jats:styled-content style="fixed-case">ADP</jats:styled-content>‐ribose) polymerase (<jats:styled-content style="fixed-case">PARP</jats:styled-content>). Moreover, oridonin‐induced <jats:italic>γ</jats:italic>H2<jats:styled-content style="fixed-case">AX</jats:styled-content> accumulation was partially abrogated by Z‐<jats:styled-content style="fixed-case">VAD</jats:styled-content>, a pan‐caspase inhibitor. Taken together, our results suggest that oridonin can effectively induce apoptosis by augmenting the expression of <jats:italic>γ</jats:italic>H2<jats:styled-content style="fixed-case">AX</jats:styled-content> in response to <jats:styled-content style="fixed-case">DNA</jats:styled-content> damage and might be a promising anti‐cancer drug candidate for the treatment of oral cancer.</jats:p>

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