Antitumor activity of spinasterol isolated from Pueraria roots.
We purified phytoestrogens from Pueraria root (Pueraria mirifica from Thailand and Pueraria lobata from Korea), which is used as a rejuvenating folk medicine in Thailand and China. Dried, powdered plant material was extracted with 100% ethanol and further separated by concentration, filtration, and thin layer silica gel chromatography. Using the fractions obtained during separation, we first investigated their cytotoxicity in several cancer cell lines from various tissues. The ethanol-extracted components (PE1, PE4) had significant antiproliferative effects on breast cancer cell lines, including MCF-7, ZR-75-1, MDA-MB-231, SK-BR-3, and Hs578T. Second, we compared these results with the cytotoxic effects of known flavonoids, sterols, and coumarins from Pueraria root. The known compounds were not as effective, and occurred in a different polarity region on HPLC. Third, further separation resulted in the isolation of eight different components (Sub PE-A to -H). One of these, PE-D, affected the growth of some breast cancer cell lines (MCF-7, MDA- MB-231) in a dose- and time-dependent manner, as well as the growth of ovarian (2774) and cervical cancer cells (HeLa). Finally, a transfection assay showed that this component had an estrogenic effect similar to 17beta - estradiol, which activates both estrogen receptor alpha (ERalpha) and ERbeta. The NMR analysis determined that spinasterol (stigmasta-7, 22-dien-3beta-ol) is an active cytotoxic component of Pueraria root.
Jeon
Gook-Che
GC
Department of Bioscience and Biotechnology/Institute of Bioscience, Sejong University, Seoul 143-747, Korea.
Park
Myoung-Soon
MS
Yoon
Do-Young
DY
Shin
Chul-Ho
CH
Sin
Hong-Sig
HS
Um
Soo-Jong
SJ
D000970:Antineoplastic Agents / Q000302:isolation & purification / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D047628:Estrogen Receptor alpha / Q000819:agonists; D047629:Estrogen Receptor beta / Q000819:agonists; D005260:Female; D006801:Humans; D028321:Plant Preparations / Q000627:therapeutic use; D018517:Plant Roots / Q000737:chemistry*; D029908:Pueraria / Q000737:chemistry*; D013265:Stigmasterol / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology; D014162:Transfection; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D028321:Plant Preparations; C031312:spinasterol; D013265:Stigmasterol