No abstract

The expression of matrix metalloproteinase-9 (MMP-9) has been implicated in the invasion and metastasis of cancer cells. Here, we found that an antitumor antibiotic, ascofuranone, inhibits invasion and MMP-9 induction induced by phorbol myristate acetate (PMA) in human cell lines. Ascofuranone also inhibits the protein expression and transcription of MMP-9 induced by tumor necrosis factor-alpha. The inhibition of MMP-9 induction was observed in human cancer cell lines as well as primary rat mesangial cells. Furthermore, as evidenced by MMP-9 promoter and electrophoretic mobility shift assays, ascofuranone specifically inhibited MMP-9 gene expression by blocking PMA-stimulated activation of activator protein-1 (AP-1). In addition, ascofuranone suppressed PMA-induced phosphorylation of Ras, Raf, MEK and extracellular signal-regulated kinase (ERK), upstream factors involved in AP-1activation, whereas the phosphorylation of p38 and JNK/mitogen-activated protein kinase was not affected by ascofuranone, suggesting that the primary target of ascofuranone for suppression of the AP-1 induction is present in upstream of ERK signaling pathway. These results suggest that the suppression of MMP-9 expression, at least in part, contributes to the antitumor activity of ascofuranone.

The content of the biologically active amino acid theanine in 15 commercial black, green, specialty, and herbal tea leaves was determined as the 2,4-dinitrophenyltheanine derivative (DNP-theanine) by a validated HPLC method. To define relative anticarcinogenic potencies of tea compounds and teas, nine green tea catechins, three black tea theaflavins, and theanine as well as aqueous and 80% ethanol/water extracts of the same tea leaves were evaluated for their ability to induce cell death in human cancer and normal cells using a tetrazolium microculture (MTT) assay. Compared to untreated controls, most catechins, theaflavins, theanine, and all tea extracts reduced the numbers of the following human cancer cell lines: breast (MCF-7), colon (HT-29), hepatoma (liver) (HepG2), and prostate (PC-3) as well as normal human liver cells (Chang). The growth of normal human lung (HEL299) cells was not inhibited. The destruction of cancer cells was also observed visually by reverse phase microscopy. Statistical analysis of the data showed that (a) the anticarcinogenic effects of tea compounds and of tea leaf extracts varied widely and were concentration dependent over the ranges from 50 to 400 microg/mL of tea compound and from 50 to 400 microg/g of tea solids; (b) the different cancer cells varied in their susceptibilities to destruction; (c) 80% ethanol/water extracts with higher levels of flavonoids determined by HPLC were in most cases more active than the corresponding water extracts; and (d) flavonoid levels of the teas did not directly correlate with anticarcinogenic activities. The findings extend related observations on the anticarcinogenic potential of tea ingredients and suggest that consumers may benefit more by drinking both green and black teas.