scholarly journals Morphine Suppresses Liver Cancer Cell Tumor Properties In Vitro and In Vivo

2021 ◽  
Vol 11 ◽  
Author(s):  
Hao-Wen Zhang ◽  
Fei Wang ◽  
Ya-Qun Zhou ◽  
San-Ping Xu ◽  
Shi-Ying Yu ◽  
...  

Morphine is an analgesic widely adopted to relieve cancer pain. A number of discrepancies, however, are presented by the published literature, with reports suggesting that opioids may either promote or inhibit the spread of cancer. It is of great significance to determine whether morphine may increase the risk of metastasis while utilized in liver cancer surgical treatment. In this study, we explore the effects of morphine on liver cancer cells in vitro and in vivo. Our results showed that morphine does not promote proliferative ability to cultured liver cancer cells. While morphine could increase the apoptosis rate of Hep3B/HepG2 cells. Furthermore, morphine could significantly inhibit the migratory and invasion ability of Hep3B/HepG2 cells. Subsequent investigations disclosed that morphine could inhibit sphere formation ability of Hep3B/HepG2 cells by using sphere formation assay. Based on nude mouse models, we demonstrated that morphine significantly reduced pulmonary tumorigenicity of Hep3B/HepG2 cells. In conclusion, our results found that morphine at clinical concentrations could suppress liver cancer cell tumor properties in vitro and in vivo, indicating the safety of morphine utilization in HCC patients’ pain management.

2014 ◽  
Vol 20 (5) ◽  
pp. 1274-1287 ◽  
Author(s):  
Chun-Han Chen ◽  
Mei-Chuan Chen ◽  
Jing-Chi Wang ◽  
An-Chi Tsai ◽  
Ching-Shih Chen ◽  
...  

2019 ◽  
Vol 39 (11) ◽  
pp. 5973-5982 ◽  
Author(s):  
SACHIKO OGASAWARA ◽  
YUTARO MIHARA ◽  
REIICHIRO KONDO ◽  
HIRONORI KUSANO ◽  
JUN AKIBA ◽  
...  

2004 ◽  
Vol 41 (5) ◽  
pp. 782-789 ◽  
Author(s):  
Toru Hisaka ◽  
Hirohisa Yano ◽  
Sachiko Ogasawara ◽  
Seiya Momosaki ◽  
Naoyo Nishida ◽  
...  

2006 ◽  
Vol 26 (8) ◽  
pp. 964-975 ◽  
Author(s):  
Hirohisa Yano ◽  
Sachiko Ogasawara ◽  
Seiya Momosaki ◽  
Jun Akiba ◽  
Sakiko Kojiro ◽  
...  

2012 ◽  
Vol 324 (1) ◽  
pp. 66-74 ◽  
Author(s):  
Evandro Fei Fang ◽  
Chris Zhi Yi Zhang ◽  
Jack Ho Wong ◽  
Jia Yun Shen ◽  
Chuan Hao Li ◽  
...  

2013 ◽  
Vol 36 (3) ◽  
pp. 247-257 ◽  
Author(s):  
Mengde Cao ◽  
Victor Prima ◽  
David Nelson ◽  
Stanislav Svetlov

2017 ◽  
Vol 474 (20) ◽  
pp. 3391-3402 ◽  
Author(s):  
Jiro Ogura ◽  
Seiji Miyauchi ◽  
Kazumi Shimono ◽  
Shengping Yang ◽  
Sathisha Gonchigar ◽  
...  

Carbidopa is used with l-DOPA (l-3,4-dihydroxyphenylalanine) to treat Parkinson's disease (PD). PD patients exhibit lower incidence of most cancers including pancreatic cancer, but with the notable exception of melanoma. The decreased cancer incidence is not due to l-DOPA; however, the relevance of Carbidopa to this phenomenon has not been investigated. Here, we tested the hypothesis that Carbidopa, independent of l-DOPA, might elicit an anticancer effect. Carbidopa inhibited pancreatic cancer cell proliferation both in vitro and in vivo. Based on structural similarity with phenylhydrazine, an inhibitor of indoleamine-2,3-dioxygenase-1 (IDO1), we predicted that Carbidopa might also inhibit IDO1, thus providing a molecular basis for its anticancer effect. The inhibitory effect was confirmed using human recombinant IDO1. To demonstrate the inhibition in intact cells, AhR (aryl hydrocarbon receptor) activity was monitored as readout for IDO1-mediated generation of the endogenous AhR agonist kynurenine in pancreatic and liver cancer cells. Surprisingly, Carbidopa did not inhibit but instead potentiated AhR signaling, evident from increased CYP1A1 (cytochrome P450 family 1 subfamily A member 1), CYP1A2, and CYP1B1 expression. In pancreatic and liver cancer cells, Carbidopa promoted AhR nuclear localization. AhR antagonists blocked Carbidopa-dependent activation of AhR signaling. The inhibitory effect on pancreatic cancer cells in vitro and in vivo and the activation of AhR occurred at therapeutic concentrations of Carbidopa. Chromatin immunoprecipitation assay further confirmed that Carbidopa promoted AhR binding to its target gene CYP1A1 leading to its induction. We conclude that Carbidopa is an AhR agonist and suppresses pancreatic cancer. Hence, Carbidopa could potentially be re-purposed to treat pancreatic cancer and possibly other cancers as well.


2013 ◽  
Vol 45 (3) ◽  
pp. 213-219 ◽  
Author(s):  
L. Wang ◽  
J. Feng ◽  
L. Da ◽  
Y. Li ◽  
Z. Li ◽  
...  

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