Progression and NSAID-induced apoptosis in malignant melanomas are independent of cyclooxygenase II

Vogt, Thomas and McClelland, M. and Jung, B. and Popova, S. and Bogenrieder, T. and Becker, B. and Rumpler, G. and Landthaler, M. and Stolz, W. (2001) Progression and NSAID-induced apoptosis in malignant melanomas are independent of cyclooxygenase II. MELANOMA RESEARCH, 11 (6). pp. 587-599. ISSN 0960-8931, 1473-5636

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Abstract

Cyclooxygenase-II (Cox-II) overexpression is involved in the progression of various subtypes of cancer. We investigated the significance of Cox-II in the progression of malignant melanomas (MMs). Using immunohistology we determined that Cox-II is riot expressed in 70 benign and malignant melanocytic tumours. Basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs) were also analysed as controls: the BCCs were consistently Cox-II negative (n = 11), whereas the SCCs showed moderate to strong Cox-II expression in 53% (n = 17). Reverse transcription-polymerase chain reaction and Western blotting of MM cell lines and MM tissues confirmed the lack of Cox-if expression in MM. However, in vitro the Cox-inhibiting nonsteroidal anti-inflammatory drug (NSAID) sulindac sulphide (SIS) was significantly more effective in inducing apoptosis than sulindac sulphone (SOS), a derivative with a negligible effect on Cox (P<0.01). The SIS doses needed for the induction of apoptosis were not significantly different in MM cell lines versus a Cox-II-positive colon carcinoma cell line (HT29). Furthermore, add-back experiments with high doses of the prostaglandins PGE(2) and PGF(2)<alpha>, major Cox-II products, did not abrogate this effect. We conclude that Cox-11 expression is not involved in the progression of MM and NSAID-induced apoptosis in MM cell lines seems to follow pathways independent of Cox-II. Nevertheless, Cox-II inhibitors are still candidates for therapy, though they act via an unknown mechanism. (C) 2001 Lippincott Williams & Wilkins.

Item Type: Article
Uncontrolled Keywords: NONSTEROIDAL ANTIINFLAMMATORY DRUGS; CELLS GENERATED INSITU; COLON-CANCER CELLS; INCREASED EXPRESSION; COLORECTAL-CANCER; LUNG METASTASIS; NUDE-MICE; IN-VIVO; INHIBITION; INDOMETHACIN; apoptosis; cyclooxygenase; melanoma; NSAIDs; sulindac
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Dermatologie und Venerologie
Depositing User: Dr. Gernot Deinzer
Date Deposited: 24 Nov 2021 08:14
Last Modified: 24 Nov 2021 08:14
URI: https://pred.uni-regensburg.de/id/eprint/40913

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