Ganoderma lucidum causes apoptosis in leukemia, lymphoma and multiple myeloma cells
Introduction
Ganoderma lucidum (Fr.) Karst (common names: Reishei, Lingzhi) is a herbal mushroom that has been used for centuries in Traditional Chinese Medicine (TCM) for its health promoting properties [1]. The fruiting bodies, spores and cultivated mycelia of G. lucidum as well as its extracts are used world-wide as ingredients in health foods, herbal medicines and dietary supplements (extracts and powdered forms) and have been used as anti-cancer agents and for prevention and treatment of various other diseases in ancient China (100 bc) [2], [3], [4], [5], [6]. Previous reports revealed that G. lucidum extract inhibited growth of several cancer cell lines including the human prostate PC-3 cancer cells, and several human bladder cancer cell lines. These cells were arrested in the G2/M phase of their cell cycle [7], [8]. Also, Ganoderma in a dose- and time-dependent manner inhibited the cell proliferation and induced apoptosis of HT-29, a human colon carcinoma cell line and MDA-MB-231 and MCF-7 breast cancer cell lines [5], [9], [10].
The phytochemical constituents of Ganoderma include polysaccharides, proteins, nucleosides, fatty acids, sterols, cerebrosides and triterpenes [11]. The triterpenoids common to Ganoderma include the ganoderic acids that may be considered as a chemical marker compound to authenticate and/or standardize Ganoderma extracts and products [12], [13].
The polysaccharide fraction of Ganoderma was shown to slow growth of sarcoma cells growing in mice [14]. The polysaccharides were able to induce the expression of IL-1, IL-6, IL-12, IFN-γ, TNF-α, GM-CSF, G-CSF, M-CSF in monocytes–macrophages and T lymphocytes which might, in part, mediate some of their anti-tumor activity [1], [15], [16]. Furthermore, these polysaccharides may also have immune enhancing properties perhaps as a consequence of their ability to stimulate cytokine production [15].
Triterpenes have been shown to inhibit growth of human hepatoma Huh-7 cells associated with G2 cell cycle arrest, but the compounds had no effect on growth of “normal” liver cell lines in vitro [2]. Moreover, the triterpene-fraction of Ganoderma inhibited the primary and metastatic tumor growth of Lewis lung carcinoma (LLC) cells implanted in mice [17].
This study investigated the anti-cancer effects of G. lucidum using a panel of 26 human cancer cell lines (16 hematologic malignancies; see Section 2). A detailed description of the characteristics of each cell line is also given in Table 1.
Section snippets
Extraction of G. lucidum and standardization by HPLC analysis
G. lucidum fruiting bodies were collected and authenticated in China by Phytomedical Research Inc. (Beijing, China), and Botanica Biosciences (Ojai, CA). A commercial standard of ganoderic acid C2 was purchased from Chromadex (Santa Ana, CA). G. lucidum fruiting bodies were extracted in water and lyophilized to yield a dark brown powder.
All solvents were HPLC (high performance liquid chromatography) grade and were purchased from Fisher (Tustin, CA). Ganoderma extract (22.28 mg) was sonicated for
HPLC analysis of G. lucidum extract
The G. lucidum extract was standardized to 0.15% ganoderic acid C2 content (Fig. 1a). Fig. 1b shows the HPLC chromatogram of ganoderic acid C2 standard eluting at a retention time of 32.9 min. Fig. 1c shows the G. lucidum extract spiked with ganoderic acid C2 standard confirming its presence at the retention time of 32.9 min.
Anti-proliferative effects of G. lucidum extract in a variety of cancer cell lines
The initial screening of 26 cancer cell lines (Table 1) was performed culturing these cells with 50 and 100 μg/ml of G. lucidum for 96 h and measuring their growth by MTT (data
Discussion
Because G. lucidum is traditionally consumed in cooked aqueous forms such as soups and tea, we conducted our evaluation on the aqueous extract of the fruiting bodies of the mushroom. We demonstrate the anti-tumor properties of an extract of G. lucidum against a variety of human leukemic, lymphoma and myeloma cell lines. After the initial screening of five herbs with known anti-cancer activities (G. lucidum, Isatis indigotica, Dendranthema morifolium, Rabdosia rubescens and Panax pseudoginseng),
Acknowledgements
We thank the Inger Foundation, Parker Hughes Trust, Marsha Diamond Fund and an NIH grant. HPK is a member of the Johnsson Cancer Center, the Molecular Biology Institute of UCLA and has the endowed Mark Goodson Chair of Oncology Research at Cedars-Sinai Medical Center/UCLA School of Medicine. This work was moreover supported in part by a fellowship (MU 1809/1) from the Deutsche Forschungsgemeinschaft to Claudia I. Müller.
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