S-adenosylmethionine induces apoptosis and cycle arrest of gallbladder carcinoma cells by suppression of JAK2/STAT3 pathways.

Szczegóły
Abstrakt

Tytuł:: S-adenosylmethionine induces apoptosis and cycle arrest of gallbladder carcinoma cells by suppression of JAK2/STAT3 pathways.
Autorzy:: Liu Y; Department of Surgery for Vascular Thyroid and Hernia, Xuzhou Central Hospital, Xuzhou, Jiangsu, 221009, People's Republic of China.
Bi T; Department of Gastroenterology, Xuzhou Central Hospital, Xuzhou, Jiangsu, 221009, People's Republic of China.
Yuan F; Department of Surgery for Vascular Thyroid and Hernia, Xuzhou Central Hospital, Xuzhou, Jiangsu, 221009, People's Republic of China.
Gao X; Department of Surgery for Vascular Thyroid and Hernia, Xuzhou Central Hospital, Xuzhou, Jiangsu, 221009, People's Republic of China.
Jia G; Department of Surgery for Vascular Thyroid and Hernia, Xuzhou Central Hospital, Xuzhou, Jiangsu, 221009, People's Republic of China. .
Tian Z; Department of Surgery for Vascular Thyroid and Hernia, Xuzhou Central Hospital, Xuzhou, Jiangsu, 221009, People's Republic of China. .
Źródło:: Naunyn-Schmiedeberg's archives of pharmacology [Naunyn Schmiedebergs Arch Pharmacol] 2020 Dec; Vol. 393 (12), pp. 2507-2515. Date of Electronic Publication: 2020 Mar 26.
Typ publikacji:: Journal Article
Język:: English
Imprint Name(s):: Original Publication: Berlin, New York, Springer Verlag.
MeSH Terms:: Apoptosis/*drug effects
Cell Cycle Checkpoints/*drug effects
Gallbladder Neoplasms/*drug therapy
Janus Kinase 2/*antagonists & inhibitors
S-Adenosylmethionine/*pharmacology
STAT3 Transcription Factor/*antagonists & inhibitors
Animals ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Apoptosis/physiology ; Cell Cycle Checkpoints/physiology ; Cell Line, Tumor ; Dose-Response Relationship, Drug ; Gallbladder Neoplasms/metabolism ; Humans ; Janus Kinase 2/metabolism ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; S-Adenosylmethionine/therapeutic use ; STAT3 Transcription Factor/metabolism ; Signal Transduction/drug effects ; Signal Transduction/physiology ; Xenograft Model Antitumor Assays/methods
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Contributed Indexing:: Keywords: Apoptosis; Cell cycle; Gallbladder carcinoma; JAK2/STAT3; S-adenosylmethionine
Substance Nomenclature:: 0 (Antineoplastic Agents)
0 (STAT3 Transcription Factor)
0 (Stat3 protein, mouse)
7LP2MPO46S (S-Adenosylmethionine)
EC 2.7.10.2 (Jak2 protein, mouse)
EC 2.7.10.2 (Janus Kinase 2)
Entry Date(s):: Date Created: 20200329 Date Completed: 20210924 Latest Revision: 20230928
Update Code:: 20240105
DOI:: 10.1007/s00210-020-01858-6
PMID:: 32219484
: Czasopismo naukowe

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S-adenosylmethionine (SAM) is a naturally occurring physiologic molecule found ubiquitously in all mammalian cells and an essential compound in many metabolic pathways. It has been reported to possess many pharmacological properties including cancer-preventive and anticancer effects. However, the precise molecular mechanism involved in its anticancer effect is not yet clear. The present study is conducted to investigate the anticancer activity and the underlying mechanisms of SAM on human gallbladder cancer cells (GBC-SD and SGC-996) in vitro and in vivo. Cells were dealt with SAM and subjected to cell viability, colony formation, Hoechst staining, apoptosis, cycle arrest, western blot, and xenograft tumorigenicity assay. Experimental results showed that SAM could significantly inhibit the growth and proliferation and induce the apoptosis as well as cell cycle arrest in G0/G1 phase of GBC-SD and SGC-996 cells in a dose-dependent manner in vitro. The expression levels of p-JAK2, p-STAT3, Mcl-1, and Bcl-XL were significantly downregulated. In addition, inhibition of the JAK2/STAT3 pathway significantly enhanced the anti-apoptotic effect of SAM, suggesting the key roles of JAK2/STAT3 in the process. More importantly, our in vivo studies demonstrated that administration of SAM could significantly decrease the tumor weight and volume and immunohistochemistry analysis proved the downregulation of p-JAK2 and p-STAT3 in tumor tissues following SAM treatment, consistent with our in vitro results. In summary, our findings indicated that SAM can inhibit cell proliferation and induce apoptosis as well as cycle arrest of GBC cells by suppression of JAK2/STAT3 pathways and the dramatic effects of SAM hinting that SAM might be a useful therapeutic option for patients suffering from gallbladder cancer.

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