Ganoderma lucidum extract induces cell cycle arrest and apoptosis in MCF‐7 human breast cancer cell

Abstract

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...

Correlation Between Antioxidative Power and Anticancer Activity in Herbs from Traditional Chinese Medicine Formulae with Anticancer Therapeutic Effect

“…Although extensive research was done on the antioxidant effect and anticancer effect of TCM herbs (Hu et al, 2002;Cheng et al, 2004Cheng et al, , 2005, in the literature only a few studies explored the relationship between antioxidative and anticancer properties of TCM herbs. In this study, five TCM herbs, which are commonly found in TCM formulae prescribed for cancer, were selected for investigation (Table 1).…”

Bacterial cupredoxin azurin as an inducer of apoptosis and regression in human breast cancer

“…In the mitochondrial apoptotic pathway, its activation depends on mitochondrial membrane disruption and the release of cytochrome c. Once activated, caspase-9 and caspase-7/3 have been shown to act on mitochondria to further disrupt their integrity, thus creating a selfamplifying feedback loop (Chandler et al, 1998;Tong et al, 2002). However, MCF-7 human breast cancer cells lack caspase-3, a crucial component of apoptosis, but they remain responsive to many apoptotic stimuli (Le et al, 2001;Liang et al, 2001;Cuvillier et al, 2001;Hu et al, 2002;McGee et al, 2002). Therefore, in the present study, we first investigated how azurin exerts its effect on certain molecular markers of apoptosis in breast cancer cells with differing p53 statuses and then studied its effect on breast cancer growth in an athymic mouse xenograft model.…”

Detection of Ganoderic Acid A in Ganoderma lingzhi by an Indirect Competitive Enzyme-Linked Immunosorbent Assay

“…They are a group of wood-degrading mushrooms with hard fruiting bodies comprising a pileus, spore, and stipe [1]. For over a century, Ganoderma species extracts have been traditionally used as a Chinese medicinal mushroom for the treatment of hepatitis [2,3], cancer-related fatigue and immune functions [4,5], neurasthenia [6], and cancer [7], where Ganoderma extract has been shown to have anticancer activity against MCF-7 and MDA-MB-231 breast cancer cells [8,9], 95-D lung cancer cells [10], PC-3 prostate cancer cells [9], and HUC-PC and MTC-11 bladder cancer cells [11]. To date, more than 100 ganoderic acids, a kind of highly oxygenated C30 lanostanetype triterpenoid, have been isolated from Ganoderma species [1] and they were active forms that exert various pharmacological activities, as mentioned above.…”