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Antitumor effects of celecoxib in COX-2 expressing and non-expressing canine melanoma cell lines
Kyoung-Won Seo1, Ye-Rin Coh2, Robert B Rebhun3
1Department of Veterinary Internal Medicine, College of Veterinary Medicine, Chungnam National University, 99 Daehakro, Yuseoung gu, Daejon 305-764, Korea.
Abstract:
Cyclooxygenase-2 (COX-2) is a potential target for chemoprevention and cancer therapy. Celecoxib, a selective COX-2 inhibitor, inhibits cell growth of various types of human cancer including malignant melanoma. In dogs, oral malignant melanoma represents the most common oral tumor and is often a fatal disease. Therefore, there is a desperate need to develop additional therapeutic strategies. The purpose of this study was to investigate the anticancer effects of celecoxib on canine malignant melanoma cell lines that express varying levels of COX-2. Celecoxib induced a significant anti-proliferative effect in both LMeC and CMeC-1 cells. In the CMeC cells, treatment of 50 μM celecoxib caused an increase in cells in the G0/G1 and a decreased proportion of cells in G-2 phase. In the LMeC cells, 50 μM of celecoxib led to an increase in the percentage of cells in the sub-G1 phase and a significant activation of caspase-3 when compared to CMeC-1 cells. In conclusion, these results demonstrate that celecoxib exhibits antitumor effects on canine melanoma LMeC and CMeC-1 cells by induction of G1-S cell cycle arrest and apoptosis. Our data suggest that celecoxib might be effective as a chemotherapeutic agent against canine malignant melanoma.
Insights
Celecoxib, a cyclooxygenase-2 (COX-2) inhibitor, shows anticancer effects against canine malignant melanoma cells. It halts cell growth by inducing cell cycle arrest and apoptosis, suggesting potential as a canine cancer therapy.
Area of Science:
- Veterinary Oncology
- Cancer Biology
- Pharmacology
Background:
- Cyclooxygenase-2 (COX-2) is a therapeutic target for cancer chemoprevention and treatment.
- Malignant melanoma is the most common and often fatal oral tumor in dogs, necessitating new therapeutic strategies.
- Celecoxib, a selective COX-2 inhibitor, has demonstrated efficacy against various human cancers.
Purpose of the Study:
- To investigate the anticancer effects of celecoxib on canine malignant melanoma cell lines.
- To evaluate celecoxib's impact on cell proliferation and cell cycle progression in canine melanoma.
- To determine if celecoxib induces apoptosis in canine malignant melanoma cells.
Main Methods:
- Culturing canine malignant melanoma cell lines (LMeC and CMeC-1) with varying COX-2 expression levels.
- Treating cell lines with celecoxib (50 μM).
- Analyzing cell proliferation, cell cycle phase distribution (G0/G1, G2, sub-G1), and caspase-3 activation.
Main Results:
- Celecoxib significantly inhibited proliferation in both LMeC and CMeC-1 canine melanoma cell lines.
- In CMeC cells, celecoxib treatment resulted in G0/G1 cell cycle arrest and reduced G2 phase proportion.
- In LMeC cells, celecoxib induced sub-G1 phase accumulation and significant caspase-3 activation, indicating apoptosis.
Conclusions:
- Celecoxib demonstrates significant antitumor effects against canine malignant melanoma cell lines.
- The drug induces G1-S cell cycle arrest and apoptosis in canine melanoma cells.
- Celecoxib holds promise as a potential chemotherapeutic agent for canine malignant melanoma.
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