Synergistic Effects of 13-cis Retinoic Acid and Arachidonic Acid Cascade Inhibitors on Growth of Head and Neck Squamous Cell Carcinoma in Vitro

1998 ◽  
Vol 118 (2) ◽  
pp. 159-164 ◽  
Author(s):  
Aaron Spingarn ◽  
Peter G. Sacks ◽  
Daniel Kelley ◽  
Andrew J. Dannenberg ◽  
Stimson P. Schantz
Keyword(s):  
Squamous Cell Carcinoma ◽  
Arachidonic Acid ◽  
Retinoic Acid ◽  
Cell Growth ◽  
Growth Inhibition ◽  
Acid Metabolism ◽  
Arachidonic Acid Metabolism ◽  
Arachidonic Acid Cascade ◽  
Hnscc Cell

Products of arachidonic acid metabolism can influence normal and malignant cell growth. In vivo, inhibitors of arachidonic acid metabolism have been associated with inhibition of tumor growth, including head and neck squamous cell carcinoma (HNSCC). This has not been evaluated extensively in vitro in an HNSCC model. Therefore we investigated the effects of several arachidonic acid cascade inhibitors (AACIs) (indomethacin, curcumin, phenidone, nordihydroguaiaretic acid, 5,8,11,14-eicosatetraynoic acid, and 13- cisretinoic acid) on the growth of two HNSCC cell lines (MDA 886Ln and 1483). We found that AACIs caused dose-dependent growth inhibition of both cell lines. In an effort to inhibit HNSCC cell growth at lower concentrations of these drugs, we evaluated the effects of a variety of AACIs in combination with 13- cis retinoic acid. We observed synergistic growth inhibition when the drugs were used in all combinations, with the exception of indomethacin. These results suggest that AACIs may have some utility in the direct treatment of HNSCC, and a strategy combining 13- cis retinoic acid with other AACIs may prove to be even more effective.

scholarly journals Targeting mTOR-CCL20 Signaling May Improve Response to Docetaxel in Head and Neck Squamous Cell Carcinoma

2021 ◽  
Vol 22 (6) ◽  
pp. 3046
Author(s):  
Ming-Huei Chou ◽  
Hui-Ching Chuang ◽  
Yu-Tsai Lin ◽  
Ming-Hsien Tsai ◽  
Ying-Hsien Kao ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Squamous Cell Carcinoma ◽  
Cell Growth ◽  
Xenograft Model ◽  
Mtor Inhibitors ◽  
Cell Proliferation And Migration ◽  
And Migration ◽  
Hnscc Cell ◽  
Proliferation And Migration

Patients with advanced head and neck squamous cell carcinoma (HNSCC) usually show a dismal prognosis. It is this worthwhile to develop new, effective therapeutic regimens for these patients, such as molecular targeted therapy, which is promising as an alternative or combination treatment for HNSCC. The mammalian target of rapamycin (mTOR) pathway, which plays an important role in the carcinogenesis of HNSCC, is the most frequently activated, and is thus worthy of further investigation. In this study, two human HNSCC cell lines, FaDu and SAS, were evaluated for cell growth with trypan blue staining and tumor growth using an orthotopic xenograft model. The immunohistochemical expression of mTOR in the subcutaneous xenograft model and the inhibitory effects of docetaxel on the growth and state of activation of the PI3K/mTOR pathway were also evaluated and examined by colony formation and Western blot, respectively. Cell proliferation and migration were measured by water-soluble tetrazolium salt (WST-1) and OrisTM cell migration assay, respectively. Furthermore, the effects of rapamycin and BEZ235, a phosphatidylinositol 3-kinases (PI3K) and mTOR inhibitor in combination with docetaxel or CCL20 were evaluated in the FaDu and SAS cells. The results showed that the expression of mTOR was significantly higher in the SAS and FaDu xenograft models than in the control. Docetaxel treatment significantly suppressed HNSCC cell proliferation and migration in vitro via the PI3K/mTOR/CCL-20 signaling pathway. Additionally, when administered in a dose-dependent fashion, mTOR inhibitors inhibited the growth and migration of the HNSCC cells. This combination was synergistic with docetaxel, resulting in almost complete cell growth and migration arrest. In conclusion, docetaxel significantly inhibited HNSCC cell proliferation and migration in vitro via the PI3K/mTOR/CCL-20 signaling pathway. The synergistic and additive activity of mTOR inhibitors combined with docetaxel shows potential as a new treatment strategy for HNSCC.

Activity of dipyrone on intraplatelet arachidonic acid metabolism: An in vitro study

1989 ◽  
Vol 21 (1) ◽  
pp. 43-50 ◽  
Author(s):  
R ABBATE ◽  
S PINTO ◽  
A GORI ◽  
R PANICCIA ◽  
M COPPO ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Acid Metabolism ◽  
In Vitro Study ◽  
Arachidonic Acid Metabolism ◽  
Vitro Study

scholarly journals Endogenous peroxidase in the nuclear envelope and endoplasmic reticulum of human monocytes in vitro: association with arachidonic acid metabolism

Blood ◽  
1984 ◽  
Vol 64 (2) ◽  
pp. 491-498 ◽  
Author(s):  
W Deimann ◽  
M Seitz ◽  
D Gemsa ◽  
HD Fahimi
Keyword(s):  
Endoplasmic Reticulum ◽  
Protein Synthesis ◽  
Arachidonic Acid ◽  
Nuclear Envelope ◽  
Culture Medium ◽  
Acid Metabolism ◽  
Arachidonic Acid Metabolism ◽  
Substantial Decrease ◽  
Prostaglandin E

Abstract he development of peroxidase (PO) reaction in the nuclear envelope (NE) and endoplasmic reticulum (ER) of monocytes differentiating in vitro and its relationship with arachidonic acid metabolism were studied. The PO, as visualized by the diaminobenzidine (DAB) technique, appeared in the NE and ER of the majority of monocytes within 24 hours of culture, with a substantial decrease thereafter. The influence of three major groups of agents--inhibitors of PO, of prostanoids, and of protein biosynthesis--upon the development of the PO reaction was examined. When aminotriazole, a PO inhibitor, was added to the culture medium, the appearance of PO was suppressed in the monocytes. The cyclooxygenase blocker, indomethacin, however, did not influence the development of PO. Also the blockers of protein synthesis, puromycin, cycloheximide, and actinomycin D, did not affect the appearance of PO. The prostanoids released from the monocytes, ie, prostaglandin E and thromboxane B2, were determined by radioimmunoassay and showed a time sequence of secretion that corresponded to the appearance of PO in the cells: a marked increase within the first 24 hours with a substantial decrease thereafter. The presence of the PO inhibitors aminotriazole and sodium azide in the culture medium produced a suppression of prostanoid release from the monocytes comparable with that of indomethacin. The data suggest that the PO in the NE and ER of differentiating monocytes in vitro (1) is associated with arachidonic acid metabolism, and (2) is not formed by de novo protein synthesis but rather by an activation process.

scholarly journals The influence of albumin and calcium on human platelet arachidonic acid metabolism

Blood ◽  
1980 ◽  
Vol 55 (3) ◽  
pp. 418-423 ◽  
Author(s):  
MJ Stuart ◽  
JM Gerrard ◽  
JG White
Keyword(s):  
Arachidonic Acid ◽  
Acid Metabolism ◽  
Human Platelet ◽  
Arachidonic Acid Metabolism ◽  
Albumin Concentration ◽  
Arachidonic Acid Release ◽  
Acid Release ◽  
External Calcium ◽  
Platelet Thromboxane

Abstract The effects of in vitro changes in calcium and albumin on human platelet arachidonic acid metabolism were evaluated. Hypoalbuminemia enhanced the conversion of released 14C-arachidonic acid from prelabeled platelet phospholipids to the metabolites of the platelet cyclooxygenase and lipoxygenase pathways. This effect was, however, associated with a decreased release of arachidonic acid in the presence of hypoalbuminemia, such that the overall conversion of released 14C- arachidonic acid to platelet thromboxane B2 was similar in the presence of physiologic albumin concentration (3.5 g/dl) or at decreased albumin concentrations of 0.7 and 0.0 g/dl. External calcium was shown to be important for optimal platelet arachidonic acid release, with maximal release occurring at 1 mM calcium.

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