Screening of promising chemotherapeutic candidates from plants against human adult T-cell leukaemia/lymphoma (X): withanolides from Physalis pruinosa

Adult T-cell leukaemia/lymphoma (ATL) is a malignancy of mature peripheral T-lymphocytes caused by human T-cell lymphotropic virus type I (HTLV-I). Administering conventional chemotherapeutic regimens used against malignant lymphomas to patients with ATL results in poor therapeutic outcomes. Previously, we isolated withanolides from the aerial parts of Physalis pruinosa and observed potent activity against leukaemia cell lines. The most effective compound showed selective toxicity against HTLV-1-infected T-cell lines compared with normal peripheral blood mononuclear cells following analysis of the structure-activity relationship. Here, we isolated 25 compounds from P. pruinosa, including 3 new compounds, and examined their antiproliferative activity against ATL-related cell lines. The EC₅₀ of withanolide E (compound 16) for MT-1 and MT-2 was 28 nM and 37 nM, respectively, which was more potent than etoposide. Additionally, compound 16 induced apoptosis, as shown by annexin V-positive cells and cleaved caspase-3.