title: Induction of premature senescence in human lung cancer by fungal immunomodulatory protein from Ganoderma tsugae.
abstract: Purified recombinant fungal immunomodulatory protein from Ganoderma tsugae (reFIP-gts) has anti-telomerase effects in human lung adenocarcinoma A549 cells. However, how reFIP-gts affects cancer cell fates remains unclear. Here, we demonstrated that reFIP-gts-treated lung cancer cells are arrested at G1 phase by flow cytometry and possess morphological phenotype consistent with cellular senescence. The senescent nature of these cells was supported by positive staining for senescence-associated beta-galactosidase activity and increased lysosomal content in A549 and CaLu-1 lung cancer cells. Arrest of cells at G1 appears to be the key means through which reFIP-gts induces premature cellular senescence in A549 cells. Finally, reFIP-gts- treated A549 cells grew more slowly and formed significantly fewer cell colonies in soft agar than untreated A549 cells. In an in vivo mouse model, A549 cells treated with reFIP-gts grew significantly slower than cells treated with PBS alone, confirming that lung tumor can be inhibited by reFIP-gts. The use of reFIP-gts may be a powerful new strategy for chemoprevention and antineoplastic therapy.
authors.affiliation: Institute of Medical and Molecular Toxicology, Chung Shan Medical University, Taichung, Taiwan, ROC.
authors.forename: Chien-Huang
authors.initials: CH
authors.lastname: Liao
authors.forename: Yi-Min
authors.initials: YM
authors.lastname: Hsiao
authors.forename: Ching-Hsiung
authors.initials: CH
authors.lastname: Lin
authors.forename: Chin-Shui
authors.initials: CS
authors.lastname: Yeh
authors.forename: James Chun-Huan
authors.initials: JC
authors.lastname: Wang
authors.forename: Chia-Hung
authors.initials: CH
authors.lastname: Ni
authors.forename: Chung-Ping
authors.initials: CP
authors.lastname: Hsu
authors.forename: Jiunn-Liang
authors.initials: JL
authors.lastname: Ko
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D016922:Cellular Senescence / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005434:Flow Cytometry; D005656:Fungal Proteins / Q000494:pharmacology*; D016193:G1 Phase / Q000187:drug effects; D005696:Galactosidases / Q000378:metabolism; D032902:Ganoderma / Q000737:chemistry*; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008247:Lysosomes / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D019098:Telomerase / Q000037:antagonists & inhibitors
chemical_list: D004791:Enzyme Inhibitors; D005656:Fungal Proteins; D007155:Immunologic Factors; D019098:Telomerase; D005696:Galactosidases