Antitumor agents, 154. Cytotoxic and antimitotic flavonols from Polanisia dodecandra.

Journal Article (Journal Article)

Three flavonols, 5,3'-dihydroxy-3,6,7,8,4'-pentamethoxyflavone [1], 5,4'-dihydroxy-3,6,7,8,3'-pentamethoxyflavone [2], and quercetin 3-O-beta-D-glucopyranosyl-7-O-alpha-L-rhamnopyranoside [3], were isolated from Polanisia dodecandra. Compound 1 showed remarkable cytotoxicity in vitro against panels of central nervous system cancer (SF-268, SF-539, SNB-75, U-251), non-small cell lung cancer (HOP-62, NCI-H266, NCI-H460, NCI-H522), small cell lung cancer (DMS-114), ovarian cancer (OVCAR-3, SK-OV-3), colon cancer (HCT-116), renal cancer (UO-31), a melanoma cell line (SK-MEL-5), and two leukemia cell lines (HL-60 [TB], SR), with GI50 values in the low micromolar to nanomolar concentration range. This substance also inhibited rubulin polymerization (IC50 = 0.83 +/- 0.2 microM) and the binding of radiolabeled colchicine to tubulin with 59% inhibition when present in equimolar concentrations with colchicine. Compound 2 also showed cytotoxicity against medulloblastoma (TE-671) tumor cells with an ED50 value of 0.98 microgram/ml. Compound 1 appears to be the first example of a flavonol to exhibit potent inhibition of tubulin polymerization and, therefore, warrants further investigation as an antimitotic agent.

Full Text

Duke Authors

Cited Authors

  • Shi, Q; Chen, K; Li, L; Chang, JJ; Autry, C; Kozuka, M; Konoshima, T; Estes, JR; Lin, CM; Hamel, E

Published Date

  • April 1995

Published In

Volume / Issue

  • 58 / 4

Start / End Page

  • 475 - 482

PubMed ID

  • 7623025

Electronic International Standard Serial Number (EISSN)

  • 1520-6025

International Standard Serial Number (ISSN)

  • 0163-3864

Digital Object Identifier (DOI)

  • 10.1021/np50118a001


  • eng