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The anti-malaria agent artesunate exhibits cytotoxic effects in primary effusion lymphoma

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Summary

Primary effusion lymphoma (PEL), caused by Kaposi’s sarcoma-associated herpesvirus (KSHV), presents as a lymphomatous effusion in body cavities and has a poor prognosis. The anti-malaria drug, artesunate, possesses anti-neoplastic potential. Therefore, we aimed to investigate its effect on KSHV-infected PEL cell lines. Artesunate inhibited cell growth and viability of PEL cells, but its effect on peripheral blood mononuclear cells was less pronounced. Artesunate induced G1 phase arrest by downregulating cyclin D1/D2, CDK2/6 and c-Myc. Artesunate increased reactive oxygen species and DNA damage, but did not affect the expression of latent and lytic genes of KSHV. It exhibited cytotoxicity through caspase-dependent and -independent pathways and reduced Bcl-xL, survivin, XIAP and c-IAP1/2 levels. Furthermore, artesunate suppressed NF-κB and AP-1 by inhibiting IκB kinase and IκBα phosphorylation as well as JunB expression. Finally, artesunate treatment attenuated PEL development in mice. Our data support that artesunate is a potential drug for PEL treatment.

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Acknowledgments

We acknowledge Dr. Harutaka Katano (National Institute of Infectious Diseases) for providing BCBL-1 and TY-1 cells. The authors thank Editage (www.editage.jp) for English language editing.

Funding

This study was partially supported by JSPS KAKENHI (17 K07175).

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Authors and Affiliations

  1. Department of Microbiology and Oncology, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa, 903-0215, Japan

    Chie Ishikawa & Naoki Mori

  2. Division of Health Sciences, Transdisciplinary Research Organization for Subtropics and Island Studies, University of the Ryukyus, 1 Senbaru, Nishihara, Okinawa, 903-0213, Japan

    Chie Ishikawa

Authors
  1. Chie Ishikawa
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  2. Naoki Mori
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Correspondence to Naoki Mori.

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No potential conflict of interest is reported by the authors.

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All animal experiments were approved by the Animal Care and Use Committee of the University of the Ryukyus (A2017175).

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Ishikawa, C., Mori, N. The anti-malaria agent artesunate exhibits cytotoxic effects in primary effusion lymphoma. Invest New Drugs 39, 111–121 (2021). https://doi.org/10.1007/s10637-020-00996-1

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  • DOI: https://doi.org/10.1007/s10637-020-00996-1

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