Khz (fusion of ganoderma lucidum and Polyporus umbellatus mycelia) induces apoptosis in A549 human lung cancer cells by generating reactive oxygen species and decreasing the mitochondrial membrane potential

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

doi:10.1007/s10068-014-0115-3

Cited by 8 publications

(4 citation statements)

References 17 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). In addition, it has been suggested that Khz induces apoptosis in human colon carcinoma HCT116 cells, accompanied by an increase in ROS, the activation of caspase 3 and increased intracellular Ca 2+ (24).…”

Section: Discussionmentioning

confidence: 86%

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: 86%

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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“…12 We suggested that Khz induces apoptosis in A549 human lung cancer cells by generating ROS and decreasing the mitochondrial membrane potential. 22 We also demonstrated that Khz-cp (crude polysaccharide extract obtained from the fusion of G. lucidum and P. umbellatus mycelia) induces apoptosis by increasing intracellular calcium levels and activating P38 and NADPH oxidasedependent generation of ROS in SNU-1 cells. 23 We fused G. lucidum and P. umbellatus mycelia to obtain Khz, which inhibited cell proliferation in human colon carcinoma HCT116 cells (Fig.…”

Section: Discussionmentioning

confidence: 71%

Khz (Fusion Product of Ganoderma lucidum and Polyporus umbellatus Mycelia) Induces Apoptosis in Human Colon Carcinoma HCT116 Cells, Accompanied by an Increase in Reactive Oxygen Species, Activation of Caspase 3, and Increased Intracellular Ca²⁺

Kim

et al. 2015

Journal of Medicinal Food

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Khz (a fusion mycelium of Ganoderma lucidum and Polyporus umbellatus mycelia) is isolated from ganoderic acid and P. umbellatus and it exerts antiproliferative effects against malignant cells. However, no previous study has reported the inhibitory effects of Khz on the growth of human colon cancer cells. In the present study, we found that Khz suppressed cell division and induced apoptosis in HCT116 cells. Khz cytotoxicity was measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Khz reduced cell viability and mitochondrial membrane potential levels and it also induced disruption of the mitochondrial membrane potential and increased calcium concentration and reactive oxygen species generation. Khz increased caspase 3, PARP, caspase 7, and caspase 9 levels, but reduced Bcl-2 protein levels. Flow cytometry showed that the percentage of HCT116 cells in the sub-G1 phase of the cell cycle increased in response to Khz treatment.

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“…This study indicates antiproliferative and proapoptotic effects of Khz and can be used as chemotherapeutic agent. 52…”

Section: Anti-proliferationmentioning

confidence: 99%

Ganoderma lucidumtargeting lung cancer signaling: A review

2017

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Lung cancer causes huge mortality to population, and pharmaceutical companies require new drugs as an alternative either synthetic or natural targeting lung cancer. The conventional therapies cause side effects, and therefore, natural products are used as a therapeutic candidate in lung cancer. Chemical diversity among natural products highlights the impact of evolution and survival of fittest. One such neglected natural product is Ganoderma lucidum used for promoting health and longevity for a longer time. The major bioconstituents of G. lucidum are mainly terpenes, polysaccharides, and proteins, which were explored for various activities ranging from apoptosis to autophagy. The bioconstituents of G. lucidum activate plasma membrane receptors and initiate various downstream signaling leading to nuclear factor-κB, phosphoinositide 3-kinase, Akt, and mammalian target of rapamycin in cancer. The bioconstituents regulate the expression of various genes involved in cell cycle, immune response, apoptosis, and autophagy in lung cancer. This review highlights the inextricable role of G. lucidum and its bioconstituents in lung cancer signaling for the first time.

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Khz (fusion of ganoderma lucidum and Polyporus umbellatus mycelia) induces apoptosis in A549 human lung cancer cells by generating reactive oxygen species and decreasing the mitochondrial membrane potential

Cited by 8 publications

References 17 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)

Khz (Fusion Product of Ganoderma lucidum and Polyporus umbellatus Mycelia) Induces Apoptosis in Human Colon Carcinoma HCT116 Cells, Accompanied by an Increase in Reactive Oxygen Species, Activation of Caspase 3, and Increased Intracellular Ca²⁺

Ganoderma lucidumtargeting lung cancer signaling: A review

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Khz (fusion of ganoderma lucidum and Polyporus umbellatus mycelia) induces apoptosis in A549 human lung cancer cells by generating reactive oxygen species and decreasing the mitochondrial membrane potential

Cited by 8 publications

References 17 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)

Khz (Fusion Product of Ganoderma lucidum and Polyporus umbellatus Mycelia) Induces Apoptosis in Human Colon Carcinoma HCT116 Cells, Accompanied by an Increase in Reactive Oxygen Species, Activation of Caspase 3, and Increased Intracellular Ca2+

Ganoderma lucidumtargeting lung cancer signaling: A review

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Khz (Fusion Product of Ganoderma lucidum and Polyporus umbellatus Mycelia) Induces Apoptosis in Human Colon Carcinoma HCT116 Cells, Accompanied by an Increase in Reactive Oxygen Species, Activation of Caspase 3, and Increased Intracellular Ca²⁺