Induction of premature senescence in human lung cancer by fungal immunomodulatory protein from Ganoderma tsugae.
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.
Liao
Chien-Huang
CH
Institute of Medical and Molecular Toxicology, Chung Shan Medical University, Taichung, Taiwan, ROC.
Hsiao
Yi-Min
YM
Lin
Ching-Hsiung
CH
Yeh
Chin-Shui
CS
Wang
James Chun-Huan
JC
Ni
Chia-Hung
CH
Hsu
Chung-Ping
CP
Ko
Jiunn-Liang
JL
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
D004791:Enzyme Inhibitors; D005656:Fungal Proteins; D007155:Immunologic Factors; D019098:Telomerase; D005696:Galactosidases