Khz (Fusion of Ganoderma lucidum and Polyporus umbellatus Mycelia) Induces Apoptosis by Increasing Intracellular Calcium Levels and Activating JNK and NADPH Oxidase-Dependent Generation of Reactive Oxygen Species

Kim, So Yeon; Kim, Ju Sung; Kim, Zoo Haye; Huang, Ren; Wang, Ren Sheng

doi:10.1371/journal.pone.0046208

Cited by 12 publications

(8 citation statements)

References 37 publications

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“…In addition, our previous study demonstrated that Khz induces apoptosis by increasing intracellular calcium levels and activating c-Jun N-terminal kinase and NADPH oxidase-dependent generation of ROS (22). These findings suggested that Khz induces apoptosis in A549 human lung cancer cells by generating reactive oxygen species and decreasing the mitochondrial membrane potential (23).…”

Section: Discussionmentioning

confidence: 85%

Induction of apoptosis in MCF-7 human breast cancer cells by Khz (fusion of Ganoderma lucidum and Polyporus umbellatus mycelium)

Kim

et al. 2015

Molecular Medicine Reports

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Abstract. Khz (fusion of Ganoderma lucidum and Polyporus umbellatus), isolated from the mycelia of G. lucidum and P. umbellatus, exerts anti-proliferative effects against malignant cells; however, its activity against human breast cancer cells remains to be elucidated. In the present study, cell proliferation was assessed using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and poptosis was examined using annexin V-propidium iodide staining and flow cytometry. The activation of caspases 7, 8 and 9 were detected in the Khz-treated cells using western blotting. The results demonstrated that Khz increased the intracellular calcium concentration and induced the production of reactive oxygen species in MCF-7 breast cancer cells, as determined using flow cytometry. The results also demonstrated that Khz inhibited cell proliferation and induced apoptosis in the MCF-7 cells. In addition, the mechanism by which Khz induces apoptosis in cancer cells was investigated. Khz induced apoptosis preferentially in transformed cells, with a minimal effect on non-transformed cells, suggesting its potential as an anticancer therapeutic agent. Oxidative stress is associated with apoptotic and non-apoptotic cell death, although pro-oxidative conditions are not a pre-requisite for apoptosis. Assessment of the activation status of caspases 7, 8 and 9 revealed that the levels of cleaved caspases were significantly increased in the cells treated with Khz. It is widely accepted that calcium signaling is important in apoptosis, and the present study observed an increase in [Ca 2+ ] i in response to Khz treatment. The anti-proliferative and pro-apoptotic effects of Khz suggest that this extract may be developed as a potential anticancer agent.

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Section: Discussionmentioning

confidence: 85%

Induction of apoptosis in MCF-7 human breast cancer cells by Khz (fusion of Ganoderma lucidum and Polyporus umbellatus mycelium)

Kim

et al. 2015

Molecular Medicine Reports

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“…This mushroom has been widely used as a herb for the promotion of health and longevity in Asian countries. There have been reports on the biological activities including histamine release-inhibitory action [25], immunomodulatory activity [11], anti-tumour cytokine production [10], differentiation-inducing activity [26], and activity to induce cancer cell apoptosis and inhibition of cancer cell death [27]–[29]. Ganoderma lucidum has been widely used by patients with different types of cancers that are too advanced for surgery, chemotherapy, or radiotherapy.…”

Section: Resultsmentioning

confidence: 99%

Anticancer Activity of Amauroderma rude

et al. 2013

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More and more medicinal mushrooms have been widely used as a miraculous herb for health promotion, especially by cancer patients. Here we report screening thirteen mushrooms for anti-cancer cell activities in eleven different cell lines. Of the herbal products tested, we found that the extract of Amauroderma rude exerted the highest activity in killing most of these cancer cell lines. Amauroderma rude is a fungus belonging to the Ganodermataceae family. The Amauroderma genus contains approximately 30 species widespread throughout the tropical areas. Since the biological function of Amauroderma rude is unknown, we examined its anti-cancer effect on breast carcinoma cell lines. We compared the anti-cancer activity of Amauroderma rude and Ganoderma lucidum, the most well-known medicinal mushrooms with anti-cancer activity and found that Amauroderma rude had significantly higher activity in killing cancer cells than Ganoderma lucidum. We then examined the effect of Amauroderma rude on breast cancer cells and found that at low concentrations, Amauroderma rude could inhibit cancer cell survival and induce apoptosis. Treated cancer cells also formed fewer and smaller colonies than the untreated cells. When nude mice bearing tumors were injected with Amauroderma rude extract, the tumors grew at a slower rate than the control. Examination of these tumors revealed extensive cell death, decreased proliferation rate as stained by Ki67, and increased apoptosis as stained by TUNEL. Suppression of c-myc expression appeared to be associated with these effects. Taken together, Amauroderma rude represented a powerful medicinal mushroom with anti-cancer activities.

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“… Kim et al (2012) in an effort to prove the anti-inflammatory effect of Vitis amurensis found out that excitotoxicity was induced not only by NMDARs but also due to the depletion of GSH levels and lipid peroxidation. MAPKs, cyclooxygenase-2 (COX-2), and pro-apoptotic proteins were also found to be active in these neurons.…”

Section: Cell Lines Models Utilized For the Study Of Glutamate-inducementioning

confidence: 99%

Researching glutamate â€“ induced cytotoxicity in different cell lines: a comparative/collective analysis/study

Κritis

Stamoula

Paniskaki

et al. 2015

Front. Cell. Neurosci.

296

229

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Although glutamate is one of the most important excitatory neurotransmitters of the central nervous system, its excessive extracellular concentration leads to uncontrolled continuous depolarization of neurons, a toxic process called, excitotoxicity. In excitotoxicity glutamate triggers the rise of intracellular Ca2+ levels, followed by up regulation of nNOS, dysfunction of mitochondria, ROS production, ER stress, and release of lysosomal enzymes. Excessive calcium concentration is the key mediator of glutamate toxicity through over activation of ionotropic and metabotropic receptors. In addition, glutamate accumulation can also inhibit cystine (CySS) uptake by reversing the action of the CySS/glutamate antiporter. Reversal of the antiporter action reinforces the aforementioned events by depleting neurons of cysteine and eventually glutathione’s reducing potential. Various cell lines have been employed in the pursuit to understand the mechanism(s) by which excitotoxicity affects the cells leading them ultimately to their demise. In some cell lines glutamate toxicity is exerted mainly through over activation of NMDA, AMPA, or kainate receptors whereas in other cell lines lacking such receptors, the toxicity is due to glutamate induced oxidative stress. However, in the greatest majority of the cell lines ionotropic glutamate receptors are present, co-existing to CySS/glutamate antiporters and metabotropic glutamate receptors, supporting the assumption that excitotoxicity effect in these cells is accumulative. Different cell lines differ in their responses when exposed to glutamate. In this review article the responses of PC12, SH-SY5Y, HT-22, NT-2, OLCs, C6, primary rat cortical neurons, RGC-5, and SCN2.2 cell systems are systematically collected and analyzed.

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Khz (Fusion of Ganoderma lucidum and Polyporus umbellatus Mycelia) Induces Apoptosis by Increasing Intracellular Calcium Levels and Activating JNK and NADPH Oxidase-Dependent Generation of Reactive Oxygen Species

Cited by 12 publications

References 37 publications

Induction of apoptosis in MCF-7 human breast cancer cells by Khz (fusion of Ganoderma lucidum and Polyporus umbellatus mycelium)

Induction of apoptosis in MCF-7 human breast cancer cells by Khz (fusion of Ganoderma lucidum and Polyporus umbellatus mycelium)

Anticancer Activity of Amauroderma rude

Researching glutamate â€“ induced cytotoxicity in different cell lines: a comparative/collective analysis/study

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