Vitex agnus-castus is a shrub belonging to the Verbenaceae family, which grows naturally and is common in the Middle East and southern Europe. Its ripened fruits have been used as a folk medicine for a long time for alleviation and/or improvement of symptoms from obstetric and gynecological diseases. Hobbs, in "Vitex: The Women's Herb", described Vitex as an effective remedy for emmeniopathy, including amenorrhea, oligomenorrhea, and menorrhagia, and that due to estrogen hypersecretion before menstruation in premenstrual tension, long-term use of V. agnus-castus reduced those symptoms and prevented relapse of the disease.
1)It also appears that the function of the corpus luteum in corpus luteum deficiency syndrome improved with V. agnus-castus due to the crinogenic effect of luteinizing hormones.Hirobe et al. reported that an antitumor effect results from the extract of ripened Israeli-grown V. agnus-castus fruits (Vitex extract) on the Chinese hamster lung carcinoma cells line V-79, and that Vitex extract has high antitumor activity.
2)Furthermore, analysis of the components of Vitex extract showed four types of new flavonoid compound and four known flavonoids.3) We investigated the cytotoxicity of Vitex extract against a normal human cell line, human uterine cervical fibroblasts (HCF), and the cancer cell lines breast carcinoma (MCF-7) and ovarian cancer (SKOV 3). Using these three cell lines, we found that the cytotoxic activity of Vitex extract may be attributed to the growth activity of the respective cell, and demonstrated the possibility that the cytotoxicity is related to the cell cycle stage.
4)To investigate the antitumor effects of Vitex extract in more detail, we examined the cytotoxicity of Vitex extract against two noncancerous and six cancerous human cell lines. The cytotoxic activity of Vitex extract was confirmed to depend on the growth rate of the cells, the cytotoxic cell death of cells with relatively low growth activity occurs through apoptosis, and apoptotic cell death results from an increase in intracellular oxidation.
MATERIALS AND METHODS
Cells and Media The breast carcinoma (MCF-7)5) and gastric signet ring carcinoma (KATO III) 6) cell lines were described previously. Cervical carcinoma (SKG-3a), colon carcinoma (COLO 201), and small cell lung carcinoma (Lu-134-A-H) cell lines were provided by the JCRB Cell Bank (Tokyo, Japan). The ovarian cancer (SK-OV-3) cell line was provided by the American Type Culture Collection (Rockville, MD, U.S.A.). Fetal fibroblasts (HE-21) were obtained from the Research Institute for Functional Peptides (Yamagata, Japan). HCF was prepared as previously described.7) Pyrrolidine dithiocarbamate (PDTC) and N-acetyl-L-cysteine (NAC) were purchased from Dojindo Laboratories and Wako Pure Chemical Industries, respectively. Preparing Ethanol Extract from Dried Ripened V. agnus-castus Fruits Dried, ripened, Israeli-grown V. agnuscastus fruits were triturated, and a crude extract was prepared from the triturate (1 g) with ethanol (10 ml) under reflux for 2 h. After...
