title: Screening of promising chemotherapeutic candidates from plants extracts.
abstract: Over the course of our studies investigating anti-proliferative properties of compounds originating from plants against human gastric adenocarcinoma (MK-1), human uterine carcinoma (HeLa), murine melanoma (B16F10), and two human T cell lymphotropic virus type 1 (HTLV-1)-infected T-cell lines (MT-1 and MT-2), we have screened 582 extracted samples obtained from a variety of parts from 370 plants. A few extracts showed anti-proliferative activity against all cell lines, but upon further investigation, toxicity toward selected cell lines was recognized. After activity-guided fractionation, isolation of the active principles was achieved. Structure-activity relationship studies identified the components and functionalities responsible for the specific selectivity against each cancer cell line. The effect of polyacetylenes against MK-1 cells was more potent than against HeLa and B16F10 cells. The compound having a 3,4-dihydroxyphenethyl group also showed an anti-proliferative effect against B16F10 cells. Some 6-methoxyflavone derivatives and 8-hydroxy furanocoumarins were good inhibitors of HeLa cell growth. The 17 compounds whose EC50 values were less than 1 nM did not show specific cellular selectivity. Because the cytotoxic effect of 24, 25-dihydrowithanolide D toward control cells was observed at a concentration about 100 times higher than those for the cancer cell lines, withanolide was identified as the most promising chemotherapeutic candidate in our experiments.
authors.affiliation: Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan. kinjojun@fukuoka-u.ac.jp.
authors.forename: Junei
authors.initials: J
authors.lastname: Kinjo
authors.affiliation: Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Nakano
authors.affiliation: Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Fujioka
authors.affiliation: Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan.
authors.forename: Hikaru
authors.initials: H
authors.lastname: Okabe
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D049109:Cell Proliferation; D006367:HeLa Cells; D006801:Humans; D017705:Lignans; D010936:Plant Extracts / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D017705:Lignans; D010936:Plant Extracts
keywords: Active principles; Activity-guided fractionation; Anti-proliferative activity; Cancer cell lines; Plant extracts; Structure–activity relationship