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Hypericin-photodynamic therapy inhibits the growth of adult T-cell leukemia cells through induction of apoptosis and suppression of viral transcription

Authors :
Lingling Xu
Xueqing Zhang
Wenzhao Cheng
Yong Wang
Kaining Yi
Zhilong Wang
Yiling Zhang
Linxiang Shao
Tiejun Zhao
Source :
Retrovirology, Vol 16, Iss 1, Pp 1-13 (2019)
Publication Year :
2019
Publisher :
BMC, 2019.

Abstract

Abstract Background Adult T-cell leukemia (ATL) is an aggressive neoplasm caused by human T-cell leukemia virus type 1 (HTLV-1). ATL carries a poor prognosis due to chemotherapy resistance. Thus, it is urgent to develop new treatment strategies. Hypericin (HY) is a new-type of photosensitizer in the context of photodynamic therapy (PDT) due to its excellent photosensitizing properties and anti-tumor activities. Results In the present study, we investigated the efficacy of hypericin in ATL cells. Clinically achievable concentrations of hypericin in association with PDT induced the inhibition of cell proliferation in ATL cell lines with minimal effect on peripheral blood CD4+ T lymphocytes. Moreover, hypericin-PDT treatment caused apoptosis and G2/M phase cell cycle arrest in leukemic cells. Western blot analyses revealed that hypericin-PDT treatment resulted in downregulation of Bcl-2 and enhanced the expression of Bad, cytochrome C, and AIF. Cleavage of caspases-3/-7/-9/-8, Bid, and PARP was increased in hypericin-PDT-treated ATL cells. In a luciferase assay, hypericin-PDT treatment was able to activate the promoter activity of Bax and p53, resulting in enhanced expression of Bax and p53 proteins. Finally, hypericin-PDT treatment suppressed the expression of viral protein HBZ and Tax by blocking the promoter activity via HTLV-1 5′LTR and 3′LTR. Conclusions Our results revealed that hypericin-PDT is highly effective against ATL cells by induction of apoptosis and suppression of viral transcription. These studies highlight the promising use of hypericin-PDT as a targeted therapy for ATL.

Details

Language :
English
ISSN :
17424690
Volume :
16
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Retrovirology
Publication Type :
Academic Journal
Accession number :
edsdoj.1111ee7a751425294ab8e196eb897eb
Document Type :
article
Full Text :
https://doi.org/10.1186/s12977-019-0467-0