Ganoderic acids suppress growth and invasive behavior of breast cancer cells by modulating AP-1 and NF-κB signaling

Jiang, Jiahua; Grieb, Brian C.; Thyagarajan, Anita; Slíva, Daniel

doi:10.3892/ijmm.21.5.577

Cited by 112 publications

(139 citation statements)

References 30 publications

(59 reference statements)

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“…Finally, Ganoderma remarkably prevented the colony formation of Skov3 cells dose-dependently. A similar potency has been shown in breast cancer and myelogenous leukemia cells (29)(30)(31). Thus, our findings strongly suggest that Ganoderma has anti-tumor effects on ovarian cancer cells.…”

Section: Discussionsupporting

confidence: 69%

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Ganoderma lucidum exerts anti-tumor effects on ovarian cancer cells and enhances their sensitivity to cisplatin

Zhao

Ye²,

Fu³

et al. 2011

Int J Oncol

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Abstract. Ganoderma lucidum is a herbal mushroom known to have many health benefits, including the inhibition of tumor cell growth. However, the effect of Ganoderma lucidum on epithelial ovarian cancer (EOC), the most fatal gynecological malignancy, has not yet been reported. In this study, we determined whether Ganoderma lucidum regulates EOC cell activity. Using several cell lines derived from EOC, we found that Ganoderma lucidum strongly decreased cell numbers in a dose-dependent manner. Ganoderma lucidum also inhibited colony formation, cell migration and spheroid formation. In particular, Ganoderma lucidum was effective in inhibiting cell growth in both chemosensitive and chemoresistant cells and the treatment with Ganoderma lucidum significantly enhanced the effect of cisplatin on EOC cells. Furthermore, Ganoderma lucidum induced cell cycle arrest at the G2/M phase and also induced apoptosis by activating caspase 3. Finally, Ganoderma lucidum increased p53 but inhibited Akt expression. Taken together, these findings suggest that Ganoderma lucidum exerts multiple anti-tumor effects on ovarian cancer cells and can enhance the sensitivity of EOC cells to cisplatin. IntroductionGanoderma lucidum is a herbal mushroom that has been widely used in preventive medicines in China and other Asian countries for over 2,000 years. It has also become a popular dietary supplement in Western countries. Ganoderma lucidum contains many different bioactive compounds, which mainly include triterpenoids, polysaccharides, nucleotides, sterols, steroids, fatty acids, proteins/peptides and trace elements (1).These substances are known to have many biological activities, including anti-tumor (2), immunomodulatory (3), anti-viral (4), anti-hepatitis (5), antioxidant (6), antihypertensive (7,8) and anti-diabetic activities (9). It has been reported that Ganoderma lucidum extracts can inhibit tumor formation and the proliferation of breast and prostate cancer, hepatoma, melanoma lymphoma and myeloid leukemia cell lines (10-12). Thus, Ganoderma lucidum could be used as a potential therapeutic agent in the form of a dietary supplement for cancer patients.Epithelial ovarian cancer (EOC) is the most common form of ovarian cancer and the leading cause of death from gynecological disorders (13). The high mortality rate of EOC is mainly due to the late diagnosis and the lack of effective treatments for the late stages of the disease (14). The most effective treatment for EOC is surgery plus platinum-based chemotherapy, with drugs such as cisplatin. However, the majority of patients ultimately experience chemoresistance and recurrence of their disease (15). Considering the high mortality rate of ovarian cancer due to the absence of effective treatment in advanced stages or during relapse, new therapeutic strategies are urgently required.In this study, we examined the effects of Ganoderma lucidum on cell proliferation and migration in several ovarian cancer cell lines. Our results show that Ganoderma lucidum inhibits cell growth, migration and...

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Section: Discussionsupporting

confidence: 69%

“…These results indicate that Ganoderma induces apoptosis in EOC cells. The pro-apoptotic effect of Ganoderma has been well established in several other cancer cell lines, such as breast, prostate and lung cancer cells (30,34,35).…”

Section: Discussionmentioning

confidence: 99%

Ganoderma lucidum exerts anti-tumor effects on ovarian cancer cells and enhances their sensitivity to cisplatin

Zhao

Ye²,

Fu³

et al. 2011

Int J Oncol

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“…It has also been reported to suppress the growth and invasive behavior of the human breast cancer cell line MDA-MB-231. This is accomplished through the downregulation of the expression of cyclin-dependent kinase 4, which regulates the G 1 /G 0 phase in the cell cycle, and through the inhibition of activator protein-1/ nuclear factor-κB-dependent secretion of urokinase-type plasminogen activators, which control cell adhesion and migration [14]. Furthermore, GAA enhances the chemosensitivity of the HepG2 human liver cancer cells to cisplatin through the inhibition of IL-6-induced signal transducers and the activation of transcription 3 phosphorylation in HepG2 cells via suppression of JAK1 and JAK2…”

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confidence: 99%

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

et al. 2016

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Ganoderma is a genus of medicinal mushroom traditionally used for treating various diseases. Ganoderic acid A is one of the major bioactive Ganoderma triterpenoids isolated from Ganoderma species. Herein, we produced a highly specific monoclonal antibody against ganoderic acid A (MAb 12?A) and developed an indirect competitive ELISA for the highly sensitive detection of ganoderic acid A in Ganoderma lingzhi, with a limit of detection of 6.10?ng/mL. Several validation analyses support the accuracy and reliability of the developed indirect competitive ELISA for use in the quality control of Ganoderma based on ganoderic acid A content. Furthermore, quantitative analysis of ganoderic acid A in G. lingzhi revealed that the pileus exhibits the highest ganoderic acid A content compared with the stipe and spore of the fruiting body; the best extraction efficiency was found when 50?% ethanol was used, which suggests the use of a strong liquor to completely harness the potential of Ganoderma triterpenoids in daily life.

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“…Cell proliferation was determined by the tetrazolium salt method (MTT method), according to the manufacturer's instructions (Promega, Madison, WI, USA). briefly, PC-3 cells were cultured in a 96-well plate and treated with PC (0-80 µg/ml) for 24, 48 and 72 h. At the end of the incubation period, the cells were harvested and absorption was determined with an ELISA plate reader at 570 nm, as previously described (46). Data points represent mean ± SD in the representative experiment of triplicate determinations.…”

Section: Methodsmentioning

confidence: 99%

“…briefly, PC-3 cells were treated with PC (0-80 µg/ml) for 24 h, harvested, and counted. Cell adhesion was determined after 1.5 h of incubation at 37˚C (46). Cell migration of PC-3 cells treated with PC (0-80 µg/ml) was assessed in Transwell chambers in the Dulbecco's modified eagle medium: nutrient mixture f-12 (DMeM/f12) medium containing 10% fetal bovine serum (fbS) (46).…”

Section: Methodsmentioning

confidence: 99%

Suppression of growth and invasive behavior of human prostate cancer cells by ProstaCaidTM: Mechanism of activity

Jiang

Eliaz²,

Slíva

2011

Int J Oncol

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Abstract. Since the use of dietary supplements as alternative treatments or adjuvant therapies in cancer treatment is growing, a scientific verification of their biological activity and the detailed mechanisms of their action are necessary for the acceptance of dietary supplements in conventional cancer treatments. In the present study we have evaluated the anti-cancer effects of dietary supplement ProstaCaid™ (PC) which contains mycelium from medicinal mushrooms (Ganoderma lucidum, Coriolus versicolor, Phellinus linteus), saw palmetto berry, pomegranate, pumpkin seed, green tea [40% epigallocatechin-3-gallate (EGCG)], Japanese knotweed (50% resveratrol), extracts of turmeric root (BCM-95 ® ), grape skin, pygeum bark, sarsaparilla root, Scutellaria barbata, eleuthero root, Job's tears, astragalus root, skullcap, dandelion, coptis root, broccoli, and stinging nettle, with purified vitamin C, vitamin D3, selenium, quercetin, citrus bioflavonoid complex, β sitosterolzinc, lycopene, α lipoic acid, boron, berberine and 3.3'-diinodolymethane (DIM). We show that PC treatment resulted in the inhibition of cell proliferation of the highly invasive human hormone refractory (independent) PC-3 prostate cancer cells in a dose-and timedependent manner with IC 50 56.0, 45.6 and 39.0 µg/ml for 24, 48 and 72 h, respectively. DNA-microarray analysis demonstrated that PC inhibits proliferation through the modulation of expression of CCND1, CDK4, CDKN1A, E2F1, MAPK6 and PCNA genes. In addition, PC also suppresses metastatic behavior of PC-3 by the inhibition of cell adhesion, cell migration and cell invasion, which was associated with the down-regulation of expression of CAV1, IGF2, NR2F1, and PLAU genes and suppressed secretion of the urokinase plasminogen activator (uPA) from PC-3 cells. In conclusion, the dietary supplement PC is a promising natural complex with the potency to inhibit invasive human prostate cancer.

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Ganoderic acids suppress growth and invasive behavior of breast cancer cells by modulating AP-1 and NF-κB signaling

Cited by 112 publications

References 30 publications

Ganoderma lucidum exerts anti-tumor effects on ovarian cancer cells and enhances their sensitivity to cisplatin

Ganoderma lucidum exerts anti-tumor effects on ovarian cancer cells and enhances their sensitivity to cisplatin

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

Suppression of growth and invasive behavior of human prostate cancer cells by ProstaCaidTM: Mechanism of activity

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