title: Induction of apoptosis in MCF‑7 human breast cancer cells by Khz (fusion of Ganoderma lucidum and Polyporus umbellatus mycelium).
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 [Ca2+]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.
authors.affiliation: Department of Radiotherapy, The First Affiliated Hospital, Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Tae Hwan
authors.initials: TH
authors.lastname: Kim
authors.affiliation: Department of Clinical Medicine, Harbin Medical University, Harbin, Heilongjiang 150000, P.R. China.
authors.forename: Ju Sung
authors.initials: JS
authors.lastname: Kim
authors.affiliation: Department of Information Engineering, Graduate School of Information Science, Nagoya University, Nagoya, Aichi 452‑0813, Japan.
authors.forename: Zoo Haye
authors.initials: ZH
authors.lastname: Kim
authors.affiliation: Department of Pharmacology, Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Ren Bin
authors.initials: RB
authors.lastname: Huang
authors.affiliation: Pharmacology and Drug Development, Korean Institute of Science and Management Career College, Seoul 158‑867, Republic of Korea.
authors.forename: Young Lye
authors.initials: YL
authors.lastname: Chae
authors.affiliation: Department of Radiotherapy, The First Affiliated Hospital, Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Ren Sheng
authors.initials: RS
authors.lastname: Wang
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D020013:Calcium Signaling / Q000187:drug effects; D020169:Caspases / Q000096:biosynthesis; D049109:Cell Proliferation / Q000187:drug effects*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D061986:MCF-7 Cells; D025282:Mycelium / Q000737:chemistry; D055492:Polyporus / Q000737:chemistry; D017382:Reactive Oxygen Species; D020940:Reishi / Q000737:chemistry; D014020:Tissue Extracts / Q000008:administration & dosage* / Q000737:chemistry
chemical_list: C579322:Khz extract; D017382:Reactive Oxygen Species; D014020:Tissue Extracts; D020169:Caspases