Changes in cell ultrastructure and inhibition of JAK1/STAT3 signaling pathway in CBRH-7919 cells with astaxanthin.

Abstract

Astaxanthin (AST), a xanthophylls carotenoid, possesses significant anticancer effects. However, to date, the molecular mechanism of anticancer remains unclear. In the present research, we studied the anticancer mechanism of AST, including the changes in cell ultrastructure, such as the mitochondrion, rough endoplasmic reticulum (RER), Golgi complex, and cytoskeleton, the inhibition of Janus kinase 1(JAK1)/transduction and the activators of the transcription-3 (STAT3) signaling pathway using rat hepatocellular carcinoma CBRH-7919 cells. Cell apoptosis was evaluated and the expressions of JAK1, STAT3, non-metastasis23-1 (nm23-1), and apoptotic gene like B-cell lymphoma/leukemia-2 (bcl-2), B-cell lymphoma-extra large (bcl-xl), proto-oncogene proteins c myc (c-myc) and bcl-2- associated X (bax) were also examined. The results showed that AST could induce cancer cell apoptosis. Under transmission electron microscope, the ultrastructure of treated cells were not clearly distinguishable, the membranes of the mitochondrion, RER, Golgi complex were broken or loosened, and the endoplasmic reticulum (ER) was degranulated. Cytoskeleton depolymerization of the microtubule system led to the collapse of extended vimentin intermediate filament bundles into short agglomerations with disordered distributions. AST inhibited the expression of STAT3, its upstream activator JAK1, and the STAT3 target antiapoptotic genes bcl-2, bcl-xl, and c-myc. Conversely, AST enhanced the expressions of nm23-1 and bax. Overall, our findings demonstrate that AST could induce the apoptosis of CBRH-7919 cells, which are involved in cell ultrastructure and the JAK1/STAT3 signaling pathway.

• Authors: Xiaodong Song, Meirong Wang, Lixia Zhang, Jinjin Zhang, Xiuwen Wang, Wenbo Liu, Xinbin Gu, Changjun Lv
• Journal: Toxicology mechanisms and methods (Toxicol Mech Methods) Vol. 22 Issue 9 Pg. 679-86 (Nov 2012) ISSN: 1537-6524 [Electronic] England
• PMID: 22889354 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• STAT3 Transcription Factor
• Stat3 protein, rat
• Xanthophylls
• astaxanthine
• Jak1 protein, rat
• Janus Kinase 1

Topics

• Animals
• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Cell Line, Tumor
• Flow Cytometry
• Fluorescent Antibody Technique
• In Situ Nick-End Labeling
• Janus Kinase 1 (antagonists & inhibitors)
• Liver Neoplasms, Experimental (enzymology, ultrastructure)
• Microscopy, Electron, Scanning
• Microscopy, Electron, Transmission
• Microscopy, Fluorescence
• Rats
• Reverse Transcriptase Polymerase Chain Reaction
• STAT3 Transcription Factor (antagonists & inhibitors)
• Signal Transduction (drug effects)
• Xanthophylls (pharmacology)