TY - JOUR
T1 - Synergistic effects of 13-cis retinoic acid and arachidonic acid cascade inhibitors on growth of head and neck squamous cell carcinoma in vitro
AU - Spingarn, A.
AU - Sacks, P. G.
AU - Kelley, D.
AU - Dannenberg, A. J.
AU - Schantz, S. R.
N1 - Funding Information:
Several arachidonic acid metabolites are detectable in head and neck squamous cell carcinoma (HNSCC), both in vivo and in vitro. Arachidonic acid can be metabolized through cyclooxygenase, the rate-limiting enzyme in the synthesis of prostaglandins, and lipoxy-genases, which catalyze the formation of hydroxy fatty acids and leukotrienes. Prostaglandin E 2 (PGE2) is one of the most abundant of the prostaglandins found in HNSCC. 1 Leukotriene B 4 (LTB4) has been detected in From the Department of Otolaryngology-Head and Neck Surgery, the Manhattan Eye, Ear and Throat Hospital (Dr. Spingarn), the Head and Neck Service, Department of Surgery (Drs. Sacks, Kelley, and Schantz), Memorial Sloan-Kettering Cancer Center, and the Department of Medicine (Dr. Dannenberg), Cornell University Medical College and Anne Fisher Nutrition Center at Strang Cancer Prevention Center. Supported in part by grant CA57166 from the National Cancer Institute. Presented in part at the Fourth Research Workshop on the Biology, Prevention, and Treatment of Head and Neck Cancer. Arlington, Va., Sept. 8-11, 1994. Reprint requests: Stimson E Schantz, MD, Head and Neck Service, Memorial Sloan-Kettering Cancer Center, 1275 York Ave., New York, NY 10021. Copyright 9 1998 by the American Academy of Otolaryngology-Head and Neck Surgery Foundation, Inc. 0194-5998/98/$5.00 + 0 23/1/77229 animal and human HNSCC in amounts similar to those of other arachidonic acid metabolites. 2 Arachidonic acid metabolites influence cellular processes including growth, differentiation, and tumorigenesis. The effects of prostaglandins include enhanced cell proliferation, growth inhibition, and induction of differentiation in vitro. 3 Exogenous prostaglandins can predispose to carcinogenesis by initiating cell division and proliferation; they enhance the transformation of hyperplastic cells into neoplastic cells and act as tumor promoters. 4 PGE 2 also inhibits the growth of certain animal and human cell lines. 5 Less is known about the effects of lipoxygenase metabolites on tumor and normal cell growth. Leukotrienes modulate cell proliferation in a variety of nonmalignant cell types 6 and may also mediate tumor cell growth. 7 The effects of arachidonic acid cascade inhibitors (AACIs) on the growth of various tumor systems have been evaluated, both in vitro and in vivo. Most of the in vivo studies show significant tumor growth inhibition by AACIs. Indomethacin, a nonsteroidal antiinflammatory drug that inhibits both cyclooxygenase and, at higher concentrations, lipoxygenase, has induced tumor regression in patients with breast cancer, 8 squamous cell carcinoma of the skin, 9 and HNSCC. 1~ Aspirin, a specific cyclooxygenase inhibitor, inhibits carcinogen-
PY - 1998
Y1 - 1998
N2 - 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, nordihydrogualaretic acid, 5,8,11,14-eicasatetraynoic 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.
AB - 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, nordihydrogualaretic acid, 5,8,11,14-eicasatetraynoic 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.
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U2 - 10.1016/S0194-5998(98)80004-1
DO - 10.1016/S0194-5998(98)80004-1
M3 - Article
C2 - 9482545
AN - SCOPUS:0031916806
VL - 118
SP - 159
EP - 164
JO - Otolaryngology - Head and Neck Surgery
JF - Otolaryngology - Head and Neck Surgery
SN - 0194-5998
IS - 2
ER -