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

doi:10.1089/jmf.2013.3135

Cited by 9 publications

(4 citation statements)

References 20 publications

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“…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). In addition, our previous study demonstrated that crude polysaccharide extract obtained from the fusion of G. lucidum and P. umbellatus mycelia induces apoptosis by increasing intracellular Ca 2+ levels and activating the P38 and NADPH oxidase-dependent generation of reactive oxygen species in SNU-1 cells (25).…”

Section: Discussionmentioning

confidence: 90%

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: 90%

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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“…It is not quite clear how overexpression or dysregulation of ANO1 contributes to cancer development. To date, evidence has been accumulated indicating that chloride channels are important for control of transepithelial transport for ion homeostasis and cell volume regulation, which is integral to regulation of cell-cycle progression and proliferation [ 19 , 21 ]. Cell-cycle progression is critically dependent on cell volume in which profound alterations in volume regulation can lead to the generation of apoptosis-resistant cells [ 50 ].…”

Section: Discussionmentioning

confidence: 99%

“…For instance, upregulation of chloride intracellular channel 1 (CLlC1) is involved in colon cancer cell migration and invasion through mediating regulatory volume decrease (RVD) mechanism [ 18 ]; and overexpression of chloride channel3 (ClC3) contributes to multiple human carcinomas such as glioma, lung, breast, and cervical tumors [ 19 ]. It has also been reported that the rise in intracellular calcium occurring during hypotonic challenge is related to RVD and involved with cancer apoptosis, indicating the interplay between calcium homeostasis and volume homeostasis [ 20 , 21 ].…”

Section: Introductionmentioning

confidence: 99%

Inhibition of Calcium-Activated Chloride Channel ANO1/TMEM16A Suppresses Tumor Growth and Invasion in Human Lung Cancer

et al. 2015

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Lung cancer or pulmonary carcinoma is primarily derived from epithelial cells that are thin and line on the alveolar surfaces of the lung for gas exchange. ANO1/TMEM16A, initially identified from airway epithelial cells, is a member of Ca2+-activated Cl- channels (CaCCs) that function to regulate epithelial secretion and cell volume for maintenance of ion and tissue homeostasis. ANO1/TMEM16A has recently been shown to be highly expressed in several epithelium originated carcinomas. However, the role of ANO1 in lung cancer remains unknown. In this study, we show that inhibition of calcium-activated chloride channel ANO1/TMEM16A suppresses tumor growth and invasion in human lung cancer. ANO1 is upregulated in different human lung cancer cell lines. Knocking-down ANO1 by small hairpin RNAs inhibited proliferation, migration and invasion of GLC82 and NCI-H520 cancel cells evaluated by CCK-8, would-healing, transwell and 3D soft agar assays. ANO1 protein is overexpressed in 77.3% cases of human lung adenocarcinoma tissues detected by immunohistochemistry. Furthermore, the tumor growth in nude mice implanted with GLC82 cells was significantly suppressed by ANO1 silencing. Taken together, our findings provide evidence that ANO1 overexpression contributes to tumor growth and invasion of lung cancer; and suppressing ANO1 overexpression may have therapeutic potential in lung cancer therapy.

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“…The ANO1 gene was first discovered in gastric stromal cancer and was initially named DOG1 (24). ANO1, as an ion channel, has a crucial role in sensing and transmitting extracellular signals to the intracellular machinery of epithelial cells, and a dysfunction of ANO1 may be involved in the development and progression of cancer of the epithelium by causing alterations of ion homeostasis and volume regulation (25,26). The ANO1 gene is involved in the development of cancer based on regulating intracellular free Ca 2+ levels (12,27).…”

Section: Discussionmentioning

confidence: 99%

Identification of candidate target genes for endometrial cancer, such as ANO1, using weighted gene co‑expression network analysis

Wang¹,

Wang

Long³

et al. 2018

Exp Ther Med

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Network-based systems biology has become an important method for analysis of high-throughput gene expression data and gene function mining. The aim of the present study was to implement a weighted gene co-expression network analysis to screen genes that were significantly correlated with the clinical phenotype of endometrial cancer based on data from The Cancer Genome Atlas. By using the function ‘pickSoftThreshold’ in R software, the optimum soft thresholding power was determined to be 4. Subsequently, a total of 2,414 expressed genes were identified among 19,791 genes from 506 samples, which were divided into 24 modules according to the different expression patterns. After analyzing the correlation between the gene expression in these 24 modules and the clinical phenotype of endometrial cancer, the anoctamin 1 (ANO1) gene was selected for further analysis. The Chi-squared test indicated that ANO1 was significantly associated with age (P=0.047), histological type (P<0.001), clinical stage (P<0.001), pathological grade (P<0.001) and positive peritoneal washing (P=0.001) of endometrial carcinoma. Kaplan-Meier survival analysis revealed that a high level of ANO1 was significantly associated with a good prognosis for endometrial cancer patients. Univariate and multivariate Cox regression analysis indicated that ANO1 is an independent prognostic factor in endometrial cancer. Further characterization of the most relevant module containing ANO1 with the database for annotation, visualization and integrated discovery tool suggested that ANO1 is involved in various pathways, including metabolic pathways. The present study suggests that ANO1 may be a potential marker for good prognosis in endometrial cancer.

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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⁺

Cited by 9 publications

References 20 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)

Inhibition of Calcium-Activated Chloride Channel ANO1/TMEM16A Suppresses Tumor Growth and Invasion in Human Lung Cancer

Identification of candidate target genes for endometrial cancer, such as ANO1, using weighted gene co‑expression network analysis

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