Abstract
BackgroundAdult 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.ResultsIn 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.ConclusionsOur 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.
Highlights
Adult T-cell leukemia (ATL) is an aggressive neoplasm caused by human T-cell leukemia virus type 1 (HTLV-1)
In the context of photodynamic therapy (PDT), inhibits the ATL cell growth by induction of apoptosis and suppression of viral transcription, indicating that hypericin is a promising drug for its characteristic of light-dependent antitumor and antiviral activity in ATL-targeted therapy
Photoactivated hypericin inhibits the proliferation of ATL cells First, we analyzed the effect of hypericin on HTLV1-associated T-cell lines (HPB-ATL-T, MT-2, C8166, and TL-Om1) and HTLV-1-negative cell line (CEMT4) by MTT assay
Summary
Adult T-cell leukemia (ATL) is an aggressive neoplasm caused by human T-cell leukemia virus type 1 (HTLV-1). 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. Adult T-cell leukemia (ATL) is an aggressive malignancy of CD4+ T lymphocytes in which the human T-cell leukemia virus type 1 (HTLV-1) has been recognized as the etiologic agent [1]. ATL develops after a long latency period, and the prognosis of ATL patients is still poor due to its resistance to chemotherapy and immunodeficiency [4,5,6]. Photodynamic therapy (PDT) is a clinical example in which optical illumination selectively activates lightsensitive drugs, termed photosensitizers, and destroys malignant cells with only mild side effects associated with systemic treatments, such as chemotherapy [12]. In addition to destroying tumor tissue by a process that can produce cellular necrosis and apoptosis, PDT produces acute inflammation and attracts leukocytes to the treated tumors [17, 18]
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