Although the pharmacology and clinical application of water extracts of Ganoderma lucidum have been extensively documented, little is known regarding its alcohol extract. In the present study, the anti-tumor effect of an alcohol extract of Ganoderma lucidum was investigated using MCF-7 cells. We found that the alcohol extract of Ganoderma lucidum inhibited cell proliferation in a dose-and time-dependent manner, which might be mediated through up-regulation of p21/Waf1 and down-regulation of cyclin D1. Furthermore, this compound can directly induce apoptosis in MCF-7 cells, which might be mediated through up-regulation of a pro-apoptotic Bax protein and not by the immune system. Our findings suggest that there are multiple mechanisms underlying the anti-tumor effects of Ganoderma lucidum. © 2002 Wiley-Liss, Inc. Key words: ganoderma lucidum; breast cancer; cell cycle; apoptosis An increasing number of natural occurring chemical compounds have been identified to be potent in the treatment of various human diseases including cancer. 1-4 Many of these substances are found in oriental herbs or plants. Recently, some chemopreventive extracts of herbs or plants have been shown to be anti-tumorigenic. [5][6][7][8] Carcinogenesis is a multistage or multimechanism process, involving the irreversible alteration of a stem cell (the "initiation" phase), followed by the clonal proliferation of the initiated stem cell (the "promotion" phase), from which the acquisition of the invasive and metastatic phenotypes are generated (the "progression" phase). 9 Cancer prevention or therapy may be accomplished at different steps of this process by different mechanisms. Mixed extract of herbs or plants might contain different chemopreventive chemotherapeutic compounds with more than one mechanism of action, thus possessing a combination of different chemopreventive or chemotherapeutic effects. It is therefore very attractive and important to identify combination effects of mixed extract of herbs or plants.Ganoderma lucidum, an oriental fungus, has been widely used as a medical drug or health-promotion product in China and other Asian countries. The fruiting bodies and cultured mycelia of Ganoderma lucidum have been demonstrated to possess anti-tumor activities, 10 -18 immunomodulatory activities, 19 -20 and neuroactive effects. 21 Although numerous studies on the effects of water extracts of GL have been reported, 10 -16 little is known regarding its alcohol extracts. It has been reported that the alcohol extract of Ganoderma lucidum can induce cell cycle arrest at transition from G1 to S phase in HeLa-cells 17 This study was designed to further investigate the anti-tumor effects of alcohol extracts of Ganoderma lucidum and elucidate the potential mechanisms using an in vitro system. We found that the alcohol extract of Ganoderma lucidum was able to induce cell cycle arrest at G1 phase and induce apoptosis in MCF-7 cells in a time-dependent manner. The mechanisms might be mediated through up-regulation of the expression of p21/Waf1-a...

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ABSTRACT. Butyl p-hydroxybenzoic acid (butyl paraben, BP) is widely used as a preservative in food and cosmetic products. Routledge et al showed that BP is weakly estrogenic in both in vitro and in vivo (rat uterotrophic) analyses. We investigated whether maternal exposures to BP during gestation and lactation periods affected the development of the reproductive organs of the F1 offspring. Pregnant Sprague-Dawley rats were injected subcutaneously with 100 or 200 mg/kg of BP from gestation day (GD) 6 to postnatal day (PND) 20. In the group exposed to 200 mg/kg of BP, the proportion of pups born alive and the proportion of pups surviving to weaning were decreased. The body weights of female offspring were significantly decreased at PND 49. The weights of testes, seminal vesicles and prostate glands were significantly decreased in rats exposed to 100 mg/kg of BP on PND 49. In contrast, the weights of female reproductive organs were not affected by BP. The sperm count and the sperm motile activity in the epididymis were significantly decreased at doses of 100 and 200 mg/kg of BP. In accordance with the sperm count in the epididymis, the number of round spermatids and elongated spermatids in the seminiferous tubule (stage VII) were significantly decreased by BP. Testicular expression of estrogen receptor (ER)-α and ER-β mRNA was significantly increased in 200 mg/kg of BP treated group at PND 90. Taken together, these results indicated that maternal exposure of BP might have adverse effects on the F1 male offspring.KEY WORDS: butyl p-hydroxybenzoic acid, male reproductive organ, maternal exposure, sperm.

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