Osthole induces human nasopharyngeal cancer cells apoptosis through Fas–Fas ligand and mitochondrial pathway

Osthole induces human nasopharyngeal cancer cells apoptosis through Fas–Fas ligand and... Nasopharyngeal carcinoma (NPC) is endemic in Southern China and Southeast Asia. The present study investigated the activity of osthole in suppressing NPC along with the underlying mechanism. Cell growth inhibition was measured using the MTT assay. Apoptosis was detected through 4ʹ,6‐diamidino‐2‐phenylindole staining and flow cytometry. Western blotting was used to identify the signaling pathway. Osthole markedly inhibited cell proliferation and induced apoptosis in the NPC cell line. Western blotting results revealed the increased activation of caspases 3, 8, and 9 and poly (ADP‐ribose) polymerase. Osthole treatment significantly reduced the expression of the antiapoptotic protein Bcl‐2 and increased the expression of the proapoptotic proteins Bax, Bak, BimL, BimS, and t‐Bid. Osthole treatment also increased the expression of Fas, FADD, TNF‐R1, TNF‐R2, DcR2, RIP, and DR5. In addition, osthole treatment significantly increased the expression levels of phosphorylated ERK1/2 and JNK1/2. These results suggested that osthole exerts cytotoxic effects on NPC cell lines mainly through apoptosis mediated by the Fas–Fas ligand and mitochondrial pathway. Osthole could be a potential anticancer agent for NPC. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Environmental Toxicology Wiley

Osthole induces human nasopharyngeal cancer cells apoptosis through Fas–Fas ligand and mitochondrial pathway

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Publisher
Wiley Subscription Services, Inc., A Wiley Company
Copyright
© 2018 Wiley Periodicals, Inc.
ISSN
1520-4081
eISSN
1522-7278
D.O.I.
10.1002/tox.22530
Publisher site
See Article on Publisher Site

Abstract

Nasopharyngeal carcinoma (NPC) is endemic in Southern China and Southeast Asia. The present study investigated the activity of osthole in suppressing NPC along with the underlying mechanism. Cell growth inhibition was measured using the MTT assay. Apoptosis was detected through 4ʹ,6‐diamidino‐2‐phenylindole staining and flow cytometry. Western blotting was used to identify the signaling pathway. Osthole markedly inhibited cell proliferation and induced apoptosis in the NPC cell line. Western blotting results revealed the increased activation of caspases 3, 8, and 9 and poly (ADP‐ribose) polymerase. Osthole treatment significantly reduced the expression of the antiapoptotic protein Bcl‐2 and increased the expression of the proapoptotic proteins Bax, Bak, BimL, BimS, and t‐Bid. Osthole treatment also increased the expression of Fas, FADD, TNF‐R1, TNF‐R2, DcR2, RIP, and DR5. In addition, osthole treatment significantly increased the expression levels of phosphorylated ERK1/2 and JNK1/2. These results suggested that osthole exerts cytotoxic effects on NPC cell lines mainly through apoptosis mediated by the Fas–Fas ligand and mitochondrial pathway. Osthole could be a potential anticancer agent for NPC.

Journal

Environmental ToxicologyWiley

Published: Jan 1, 2018

Keywords: ; ; ; ;

References

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