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Effects of triptolide on histone acetylation and HDAC8 expression in multiple myeloma in vitro

  • Original Article
  • Published:
Chinese Journal of Cancer Research

Abstract

Objective

Multiple myeloma is a kind of malignant plasma cell disease that originated from B lymphocyte and secrete great amount of monoclonal immunoglobulin. It is still one of the refractory diseases at present. Numerous studies show that there is an intensive relationship between the disequilibrium of histone acetylation and the occurance of multiple myeloma. Here we investigated the effect of triptolide(TPL) on the proliferation, apoptosis, histone H3 and H4 acetylation and expression of histone deacetylase 8 (HDAC8) in vitro, to explore its anti-myeloma mechanism.

Methods

The effect of triptolide on the growth of RPMI8226 was studied by 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium(MTT) assay. Apoptosis was detected by Hoechst 33258 staining. The protein expressions of acetyl-histone H3 and H4 were determined by Western blot, and the expression of HDAC8 was assessed by RT-PCR, Western blot and confocal microscopy.

Results

Triptolide inhibited the proliferation of RPMI8226 and induced apoptosis in a time- and dose-dependent manner. The 36h IC50 value was (105.370 ± 0.189)nmol/L. Triptolide increased the acetylation of histone H3 and H4 greatly. Furthermore, triptolide significantly down-regulated the mRNA and protein expression of HDAC8.

Conclusion

Triptolide can inhibit proliferation and induce apoptosis of RPMI8226 significantly. Triptolide reduces the expression of HDAC8 in order to increase the histone H3 and H4 acetylation, which is possibly the anti-myeloma mechanism of triptolide.

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Authors and Affiliations

  1. Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China

    Fei Zhao, Ling-lan Zeng, Yan Chen, Rui Li, Yuan Liu, Lu Wen, Yi-quan Cheng & Chun Zhang

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  1. Fei Zhao
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  2. Ling-lan Zeng
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  3. Yan Chen
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  4. Rui Li
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  5. Yuan Liu
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  6. Lu Wen
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  7. Yi-quan Cheng
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  8. Chun Zhang
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Correspondence to Chun Zhang.

Additional information

This work was supported by the National Natural Science Foundation of China(No.30700882)

Contributed equally to this study.

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Zhao, F., Zeng, Ll., Chen, Y. et al. Effects of triptolide on histone acetylation and HDAC8 expression in multiple myeloma in vitro . Chin. J. Cancer Res. 22, 148–155 (2010). https://doi.org/10.1007/s11670-010-0148-y

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  • DOI: https://doi.org/10.1007/s11670-010-0148-y

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