Bortezomib induces apoptosis by interacting with JAK/STAT pathway in K562 leukemic cells.
In the current study, we aimed to identify the cytotoxic and apoptotic effects of bortezomib (BOR) on human K562 chronic myelogenous leukemia cells and to evaluate the potential roles of Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway members STAT3, STAT5, and JAK2 on BOR-induced cell death of leukemic cells. Cell viability was assessed via trypan blue dye exclusion test, and cytotoxicity of the BOR-treated cells was conducted by 2,3-bis(2-methoxy-4-nitro-5-sulphophenyl)-2H-tetrazolium-5-carboxanilide inner salt (XTT) assay. The relative messenger RNA (mRNA) expression levels of STAT3, STAT5A, STAT5B, and JAK2 were analyzed by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). On the other hand, their protein expression levels were detected by western blot method. The obtained results indicated that BOR treatment reduced cell viability and induced leukemic cell apoptosis in a dose- and time-dependent manner as compared to untreated control cells. While mRNA expression levels of STAT5A, STAT5B, and STAT3 were significantly reduced following BOR treatment when compared to untreated controls, it had no effect upon JAK2 mRNA expression. As for protein levels, STAT expressions were downregulated after BOR treatment especially at 72nd and 96th hours. Our results pointed out that BOR treatment had a significant potential of being an anticancer agent for chronic myelogenous leukemia therapy, and this effect could be due to the expressional downregulations of JAK/STAT pathway members.
Department of Medical Biology, Medical Faculty, Ege University, Bornova, 35100, Izmir, Turkey, selvi.nur@gmail.com.
Nur
N
Selvi
Burçin Tezcanli
BT
Kaymaz
Cumhur
C
Gündüz
Cağdaş
C
Aktan
Hatice Demet
HD
Kiper
Fahri
F
Sahin
Melda
M
Cömert
Ali Fatih
AF
Selvi
Buket
B
Kosova
Güray
G
Saydam
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001897:Boronic Acids / Q000494:pharmacology*; D000069286:Bortezomib; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D053612:Janus Kinases / Q000502:physiology*; D020014:K562 Cells; D011719:Pyrazines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D050791:STAT Transcription Factors / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
D000970:Antineoplastic Agents; D001897:Boronic Acids; D011719:Pyrazines; D012333:RNA, Messenger; D050791:STAT Transcription Factors; D000069286:Bortezomib; D053612:Janus Kinases