Receptor Independent Effect of Melatonin on Proliferation of Canine Osteosarcoma

Cammarata, Alexis

Receptor Independent Effect of Melatonin on Proliferation of Canine Osteosarcoma

Persistent URL

http://hdl.handle.net/10456/42756

Author(s)

Cammarata, Alexis

Date Issued

April 3, 2017

Abstract

Melatonin displays anticancer effects in human and canine osteosarcoma but the precise mechanism of action remains unknown. Osteosarcoma (OSA) is the most common form of bone cancer in humans and canines resulting in a grim prognosis. Human and canine OSA share many similar characteristics, therefore C-OSA can be used to examine potential chemotherapeutics for humans and canines. In this study, the mechanism of action for melatonin was investigated in canine osteosarcoma (C-OSA) 32 and 40 cell lines. Quantitative PCR showed that C-OSA 32 and 40 both contain melatonin receptor 1 (MT1) mRNA however, only C-OSA 32 contains mRNA levels of melatonin receptor 2 (MT2). Results from proliferation assays indicated that 1mM melatonin had no effect on cell proliferation in C-OSA 32 but suppressed proliferation in C-OSA 40 approximately 40% however, this effect was not blocked by the melatonin antagonist luzindole. Increased levels of cyclooxygenase-2 (COX-2) have been shown to increase levels of cyclin dependent kinase A1 (CDKA1) which both indicate a poor prognosis for cancer patients. Therefore, levels of COX-2 and CDKA1 mRNA were analyzed after treatment with melatonin but neither pathway showed a significant decrease suggesting an alternative route for melatonin mediated proliferation. These results suggest melatonin decreases proliferation in C-OSA 40 in a receptor independent way, and the mechanism of action in these cells remains unresolved.

Major

Biochemistry

First Reader(s)

Kleinschmidt, Ann