title: Screening of promising chemotherapeutic candidates from plants against human adult T-cell leukemia/lymphoma (II): apoptosis of antiproliferactive principle (24,25-dihydrowithanolide D) against ATL cell lines and structure-activity relationships with withanolides isolated from solanaceous plants.
abstract: Adult T-cell leukemia/lymphoma (ATL) is an incurable peripheral T-cell malignancy caused by human T-cell lymphotropic virus type I. In our preceding paper, 214 extracts from 162 plants were screened to elucidate the antiproliferative principles against ATL cell lines. Several withanolides were isolated and the structure-activity relationships (SAR) examined. To extend the search for SAR, 31 further withanolides, previously isolated from solanaceous plants, were tested against ATL cell lines. The presence of a 4β-hydroxy group as well as a 5β,6β-epoxy group appeared to be essential for the activity. In contrast, the presence of a sugar moiety at either the 3- or the 27-position led to a reduction in the activity. Furthermore, 24,25-dihydrowithanolide D (13) was identified as the most potent inhibitor, showing selective toxicity against ATL cell lines by inducing apoptotic cell death.
authors.affiliation: Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Nakano
authors.forename: Kenji
authors.initials: K
authors.lastname: Ishitsuka
authors.forename: Hiroo
authors.initials: H
authors.lastname: Katsuya
authors.forename: Naoko
authors.initials: N
authors.lastname: Kunami
authors.forename: Rumiko
authors.initials: R
authors.lastname: Nogami
authors.forename: Yuka
authors.initials: Y
authors.lastname: Yoshimura
authors.forename: Michika
authors.initials: M
authors.lastname: Matsuda
authors.forename: Mio
authors.initials: M
authors.lastname: Kamikawa
authors.forename: Ryota
authors.initials: R
authors.lastname: Tsuchihashi
authors.forename: Masafumi
authors.initials: M
authors.lastname: Okawa
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Ikeda
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Nohara
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tamura
authors.forename: Junei
authors.initials: J
authors.lastname: Kinjo
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000378:metabolism; D015394:Molecular Structure; D019657:Solanaceae / Q000737:chemistry*; D013329:Structure-Activity Relationship; D054358:Withanolides / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D054358:Withanolides