The influence of opioids on matrix metalloproteinase-2 and -9 secretion and mRNA levels in MCF-7 breast cancer cell line.
Matrix metalloproteinases (MMPs) are proteolytic enzymes involved in degradation of extracellular matrix, a process that initiates uncontrolled spread of proliferating cancer cells and therefore plays a crucial role in cancer invasion and metastasis. Compounds able to modulate MMP activity may become important tools in cancer research. In the present study we examined the effect of two μ-selective opioids, morphine and endomorphin-2 (EM-2) on the production of MMP-2 and MMP-9 in MCF-7 cells. We report that both opioids time- and concentration-dependently inhibited the expression and secretion of these MMPs. The observed effect was not reversed by naloxone (Nal). Further experiments showed that morphine and EM-2 decreased endothelial nitric oxide synthase (eNOS) mRNA level and nitric oxide (NO) secretion in MCF-7 cells. These findings indicate that attenuation of MMP secretion by opioids was not mediated by opioid receptors but was under the control of nitric oxide system.
Gach
Katarzyna
K
Department of Biomolecular Chemistry, Medical University of Lodz, Mazowiecka 6/8, 92-215, Lodz, Poland.
Szemraj
Janusz
J
Wyrębska
Anna
A
Janecka
Anna
A
D000701:Analgesics, Opioid / Q000627:therapeutic use*; D015415:Biomarkers; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis*; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
D000701:Analgesics, Opioid; D015415:Biomarkers; D012333:RNA, Messenger; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9