Hispolon from Phellinus linteus has antiproliferative effects via MDM2-recruited ERK1/2 activity in breast and bladder cancer cells

Lu, Te‐Ling; Huang, Guan Jhong; Lu, Te Jung; Wu, Jin; Wu, Chieh Hsi; Yang, Tung Chuan; Iizuka, Akira; Chen, Yuh Fung

doi:10.1016/j.fct.2009.05.023

Cited by 76 publications

(47 citation statements)

References 30 publications

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“…Nevertheless, the cultivated mushroom or cultured mycelia of P. linteus exhibited biological activities comparable to the wild-grown mushroom, and produced an abundant amount of yellow pigments containing mainly styrylpyrones with various biological activities. 28,29,34,[52][53][54][55][56][57]60,64,[72][73][74][75] In addition, the adverse effects of the medicinal mushrooms Phellinus and Inonotus have not been reported until now. Methanolic extracts of I. xeranticus did not show acute toxicity up to 2 g kg À1 in mice, and the LD 50 values of these extracts were above 2 g kg À1 , indicating the safe nature of these mushrooms.…”

Section: Discussionmentioning

confidence: 99%

Styrylpyrone-class compounds from medicinal fungi Phellinus and Inonotus spp., and their medicinal importance

2011

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Members of the genera Phellinus and Inonotus, including P. linteus, P. igniarius, P. ribis, I. obliquus and I. xeranticus are well-known medicinal fungi (mushrooms) and have been used in treatment of cancer, diabetes, bacterial and viral infections and ulcer. Adverse effects of these medicinal mushrooms have not yet been reported, indicating the safe nature of these mushrooms. Polysaccharides, particularly b-glucan, are considered the compounds responsible for the biological activity of medicinal mushrooms. However, there is only a limited amount of evidence to indicate that polysaccharides are in fact responsible for the biological effects of these medicinal mushrooms. Recently, many research groups have begun identification of active low-MW compounds in medicinal mushrooms, with a focus on the yellow polyphenol pigments, which are composed of a styrylpyrone class of compounds. Interestingly, a representative group of medicinal fungi, including P. linteus, P. igniarius, P. ribis, I. obliquus and I. xeranticus were shown to produce a large and diverse range of styrylpyrone-type polyphenol pigments that exhibited various biological activities, including anti-oxidative, anti-inflammatory, cytotoxic, anti-platelet aggregation, anti-diabetic, anti-dementia and anti-viral effects. Styrylpyrone pigments in mushrooms are thought to have a role similar to that of flavonoids in plants. The unique and unprecedented carbon skeleton of fused styrylpyrone might be an attractive molecular scaffold for pharmacological applications. In this review, the structural diversity, biological effects and biogenesis of styrylpyrone-class polyphenols from medicinal fungi are described.

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Section: Discussionmentioning

confidence: 99%

Styrylpyrone-class compounds from medicinal fungi Phellinus and Inonotus spp., and their medicinal importance

2011

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“…these apoptotic events were accompanied by the collapse of mitochondrial membrane potential, the release of cytochrome c and the activation of caspase-3, suggesting that hispolon specifically induced the cell death of epidermoid cells through a mitochondria-mediated apoptotic pathway (21). as recently demonstrated, hispolon inhibited the proliferation and induced the apoptosis of breast and bladder cancer cells, independently of the tumor suppressor p53 status in these cells (28). the inhibition of cell growth was mediated by cell cycle arrest at the G2/m phase through the up-regulation of expression of cyclin-dependent kinase inhibitor p21, whereas apoptosis was linked to the ErK1/2-dependent induction of caspase-7 and parp in breast and bladder cancer cells (28).…”

Section: The Anticancer Activity Of Isolated Compoundsmentioning

confidence: 99%

“…as recently demonstrated, hispolon inhibited the proliferation and induced the apoptosis of breast and bladder cancer cells, independently of the tumor suppressor p53 status in these cells (28). the inhibition of cell growth was mediated by cell cycle arrest at the G2/m phase through the up-regulation of expression of cyclin-dependent kinase inhibitor p21, whereas apoptosis was linked to the ErK1/2-dependent induction of caspase-7 and parp in breast and bladder cancer cells (28). notably, hispolon down-regulated the expression of the mdm2 proto-oncogene through ErK1/2-mediated mdm2 ubiquitination suggesting the use of hispolon for cancer treatment (28).…”

Section: The Anticancer Activity Of Isolated Compoundsmentioning

confidence: 99%

“…the inhibition of cell growth was mediated by cell cycle arrest at the G2/m phase through the up-regulation of expression of cyclin-dependent kinase inhibitor p21, whereas apoptosis was linked to the ErK1/2-dependent induction of caspase-7 and parp in breast and bladder cancer cells (28). notably, hispolon down-regulated the expression of the mdm2 proto-oncogene through ErK1/2-mediated mdm2 ubiquitination suggesting the use of hispolon for cancer treatment (28). recently, isolated phellifuropyranone a and meshimakobnol a and B demonstrated antiproliferative activity against mouse melanoma and human lung cancer cells in vitro, respectively (29), although the molecular mechanism responsible for their activity was not addressed (29).…”

Section: The Anticancer Activity Of Isolated Compoundsmentioning

confidence: 99%

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Medicinal mushroom Phellinus linteus as an alternative cancer therapy

Slíva

2010

Experimental and Therapeutic Medicine

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Abstract. alternative cancer treatment with nutritional/dietary supplements containing a wide variety of herbal products is on the rise in Western countries. recent epidemiological studies have suggested that mushrooms may prevent against different types of cancers. Phellinus linteus is a well-known Oriental medicinal fungus with a variety of biological activities, including immunomodulatory or direct antitumor activities. the activity of P. linteus and its extracts is associated with the presence of polysaccharides, their peptide/protein complexes and other low molecular weight complexes. polysaccharide fractions isolated from P. linteus were found to be related to the increased activity of immune cells such as the production of cytokines by macrophages and B-cells or the increased cytotoxic activity of natural killer cells. moreover, P. linteus was found to modulate the expression or activity of various genes involved in cell proliferation, apoptosis, angiogenesis, invasive behavior and chemoprevention. Finally, P. linteus extracts demonstrated tumor regression in three independent case reports, suggesting that an extract from P. linteus or a dietary supplement based on the extract from P. linteus may have potential use for the alternative treatment of cancer. Contents1. introduction 2. Phellinus linteus 3. the anticancer activity of isolated compounds 4. the anticancer activity of P. linteus extracts 5. human studies 6. conclusions Introductionthe popularity of complementary and alternative medicine (cam) is steadily increasing among cancer patients, and cam represents one of the fastest growing treatment modalities in the uS (1). the most commonly used cam includes acupuncture, mind-body approaches and dietary supplements. Specifically, among cancer patients, the use of CAM ranges between 30 and 75% worldwide and includes dietary approaches, herbal and other biologically based treatments (2). For example, herbal therapies are used by more than 12% of the uS population each year, resulting in annual out-ofpocket expenses above $5 billion (3). in spite of the popularity of alternative cancer treatments with nutritional/dietary supplements among patients, sometimes based on the anecdotic evidence, cam therapies are in many cases labeled as 'pseudoscience' (4). Therefore, rigorous scientific testing and safety evaluation of dietary supplements must be performed, after which clinicians can recommend the use of a particular dietary supplement (5).Some of the popular, widely used dietary supplements are based on dried mushrooms or mushroom extracts. notably, three recent epidemiological studies from asia demonstrated an inverse correlation between mushroom intake and gastric, gastrointestinal and breast cancer, respectively (6-8). the anticancer activities of mushrooms were usually associated with the stimulation of the immune system by polysaccharides, predominantly β-glucans (9). On the other hand, mushrooms contain minerals, vitamins (e.g., thiamin, riboflavin, ascorbic acid and vitamin d), amino acids and other...

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“…In addition, HPL has demonstrated antitumor effects in various types of cancer cells, including melanoma, leukemia, hepatocarcinoma, bladder cancer and gastric cancer cells (16)(17)(18)(19)(20).…”

Section: Introductionmentioning

confidence: 99%

Hispolon as an inhibitor of TGF-β-induced epithelial-mesenchymal transition in human epithelial cancer cells by co-regulation of TGF-β-Snail/Twist axis

et al. 2017

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Abstract. Hispolon (HPL), isolated from Phellinus linteus, has been used to treat various types of pathology, including inflammation, gastroenteric disorders, lymphatic diseases and numerous cancer subtypes. HPL has previously been reported to demonstrate a significant therapeutic efficacy against various types of cancer cells, including melanoma, leukemia, hepatocarcinoma, bladder and gastric cancer cells. However, its potential role in the epithelial-mesenchymal transition (EMT) has not been demonstrated. The present study investigated the effects of HPL on the EMT. Transforming growth factor β (TGF-β) induced enhanced cell migration and invasion, EMT-associated phenotypic changes. In the present study, HPL recovered the reduction of E-cadherin expression level in TGF-β treated cancer cells, which was regulated by the expression of Snail and Twist. HPL downregulated Snail and Twist, an effect that was enhanced by TGF-β. These findings provide novel evidence that HPL suppresses cancer cell migration and invasion by inhibiting EMT. Therefore, HPL may be a potent anticancer agent, inhibiting metastasis.

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Hispolon from Phellinus linteus has antiproliferative effects via MDM2-recruited ERK1/2 activity in breast and bladder cancer cells

Cited by 76 publications

References 30 publications

Styrylpyrone-class compounds from medicinal fungi Phellinus and Inonotus spp., and their medicinal importance

Styrylpyrone-class compounds from medicinal fungi Phellinus and Inonotus spp., and their medicinal importance

Medicinal mushroom Phellinus linteus as an alternative cancer therapy

Hispolon as an inhibitor of TGF-β-induced epithelial-mesenchymal transition in human epithelial cancer cells by co-regulation of TGF-β-Snail/Twist axis

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