TY - JOUR
T1 - Matrix metalloproteinase 2 secretion in WEHI 164 fibrosarcoma cells is nitric oxide-related and modified by morphine
AU - Shariftabrizi, Ahmad
AU - Nifli, Artemissia Phoebe
AU - Ansari, Mohammad
AU - Saadat, Farshid
AU - Reza Ebrahimkhani, Mohammad
AU - Alizadeh, Nastaran
AU - Nasseh, Azadeh
AU - Alexaki, Vassilia Ismini
AU - Dehpour, Ahmad Reza
AU - Castanas, Elias
AU - Khorramizadeh, Mohammad Reza
N1 - Funding Information:
This work was partially supported by a University of Crete Research Committee grant. APN holds a scholarship from the Public Benefit Foundation A.S. Onassis.
PY - 2006/1/13
Y1 - 2006/1/13
N2 - Matrix metalloproteinases (MMP) are ubiquitous enzymes involved in extracellular matrix remodeling, and as a consequence in a number of physiological and pathological states, including development, wound healing and cancer. A crucial feature of cancer progression and metastasis is the disruption of extracellular matrix, and spreading of proliferating cancer cells. Modulation of MMP is a main target of cancer research. Using the mouse fibrosarcoma cell line WEHI 164, producing high amounts of MMP-2, we investigated whether we could modulate its production. We report that MMP-2 is under the control of nitric oxide (NO)/nitric oxide synthase (NOS) system. In addition, we show that NOS activity is controlled by opioids in a non-opioid receptor-related manner. Finally, we provide evidence that morphine, when administrated at low, non-toxic concentrations (< 10- 9 M) attenuates MMP-2 activity. We conclude that, as morphine is able to decrease metalloproteinase activity via the NO/NOS system, it may have a place in the treatment of several sarcomas including fibrosarcoma.
AB - Matrix metalloproteinases (MMP) are ubiquitous enzymes involved in extracellular matrix remodeling, and as a consequence in a number of physiological and pathological states, including development, wound healing and cancer. A crucial feature of cancer progression and metastasis is the disruption of extracellular matrix, and spreading of proliferating cancer cells. Modulation of MMP is a main target of cancer research. Using the mouse fibrosarcoma cell line WEHI 164, producing high amounts of MMP-2, we investigated whether we could modulate its production. We report that MMP-2 is under the control of nitric oxide (NO)/nitric oxide synthase (NOS) system. In addition, we show that NOS activity is controlled by opioids in a non-opioid receptor-related manner. Finally, we provide evidence that morphine, when administrated at low, non-toxic concentrations (< 10- 9 M) attenuates MMP-2 activity. We conclude that, as morphine is able to decrease metalloproteinase activity via the NO/NOS system, it may have a place in the treatment of several sarcomas including fibrosarcoma.
KW - Fibrosarcoma cell (WEFI 164)
KW - Nitric oxide
KW - Nitric oxide synthase
KW - Opioid (morphine)
KW - Opioid receptors (mu, delta, kappa)
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U2 - 10.1016/j.ejphar.2005.11.043
DO - 10.1016/j.ejphar.2005.11.043
M3 - Article
C2 - 16386243
AN - SCOPUS:29844437146
SN - 0014-2999
VL - 530
SP - 33
EP - 39
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 1-2
ER -