title: Screening of promising chemotherapeutic candidates against human adult T-cell leukemia/lymphoma from plants: active principles from Physalis pruinosa and structure-activity relationships with withanolides.
abstract: Adult T-cell leukemia/lymphoma (ATL) is a peripheral T-cell malignancy caused by human T-cell lymphotropic virus type I (HTLV-1). Clinical manifestations of ATL range from smoldering to chronic, lymphoma and acute subtypes. Patients with acute and lymphoma-type ATL require therapeutic intervention. Conventional chemotherapeutic regimens used against other malignant lymphoma have been administered to ATL patients, but the therapeutic outcomes of acute and lymphoma-type ATL remain very poor. In this study, 214 extracts from 162 plants belonging to 65 families were screened for the purpose of elucidating the anti-proliferative effect against HTLV-1-infected T-cell lines. Extracts from aerial parts of Physalis pruinosa showed potent inhibitory effect. We isolated five withanolides from the extracts by activity-guided fractionation and examined the structure-activity relationships. The presence of a 5β,6β-epoxy function is suggested to be essential for the activity, and the most active principle showed selective toxicity to HTLV-1-infected T-cell lines.
authors.affiliation: Fukuoka University, Jonan-ku, Fukuoka, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Nakano
authors.forename: Kenji
authors.initials: K
authors.lastname: Ishitsuka
authors.forename: Takahiro
authors.initials: T
authors.lastname: Hatsuse
authors.forename: Ryota
authors.initials: R
authors.lastname: Tsuchihashi
authors.forename: Masafumi
authors.initials: M
authors.lastname: Okawa
authors.forename: Hikaru
authors.initials: H
authors.lastname: Okabe
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tamura
authors.forename: Junei
authors.initials: J
authors.lastname: Kinjo
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000378:metabolism*; D032321:Physalis / Q000737:chemistry*; D010936:Plant Extracts / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D054358:Withanolides / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D010936:Plant Extracts; D054358:Withanolides