Ropivacaine and lidocaine inhibit proliferation of non-transformed cultured adult human fibroblasts, endothelial cells and keratinocytes

Abstract

Local anaesthetics are known to affect a variety of cell functions, many of which are involved in the inflammatory response. Local anaesthetics have also been shown to influence cell proliferation. The aim of this study was to examine the effect of two local anaesthetics (ropivacaine and lidocaine) on cell proliferation of cultured human fibroblasts, vascular endothelial cells and epithelial cells, i.e. keratinocytes, as earlier studies have not included primary human cell types. Significant inhibition of fibroblast proliferation was observed with concentrations of 50 microM ropivacaine or 100 microM lidocaine in 1% newborn calf serum and 500 microM ropivacaine or lidocaine in 10% newborn calf serum. The proliferation of endothelial cells was significantly inhibited by 1 mM ropivacaine in 5% human serum and 500 microM ropivacaine or 100 microM lidocaine in 40% human serum. Significant inhibition was not obtained with lidocaine when these cells were cultured in 5% HS. Significant inhibition of keratinocytes was obtained with 100 microM ropivacaine and 500 microM lidocaine. The effective concentrations are within the range of therapeutical concentrations in vivo and there seems to be a general correlation between the local anaesthetic potency and the inhibiting effect on cell proliferation. This suggest a mechanism by which local anaesthetics may exhibit anti-hyperproliferative effects in clinical situations.

Skin biopsy and quantitative sensory testing do not predict response to lidocaine patch in painful neuropathies

“…4 In vitro studies indicate that lidocaine has antiproliferative effects upon keratinocytes, and antiinflammatory effects-for example, inhibition of release of the chemokine MCP-1, a molecule implicated in the genesis of neuropathic pain in animal models. 12,13,24 Future studies of the mechanism and site of action of the lidocaine patch in peripheral neuropathic pain might also consider the possibility of effects mediated in part via modulation of resident cells in the skin.…”

Ectopic expression of clusterin/apolipoprotein J or Bcl-2 decreases the sensitivity of HaCaT cells to toxic effects of ropivacaine

“…However, bupivacaine was shown to have a more potent cytotoxic effect than ropivacaine on the same cell types [6]. Other local anesthetics appear to have similar effects on various cell types [9][10][11][12][13][14]. Prilocaine was found to induce apoptosis in mouse and human osteoblastic cells [11] and lidocaine was shown to inhibit the proliferation of normal human fibroblasts, endothelial cells and keratinocytes [12], while enhancing bleomycin A 2 cytotoxicity and DNA strand breakage in murine leukemia cells and human head and neck carcinoma cells [13] and imparing corneal wound healing [14].…”

“…Other local anesthetics appear to have similar effects on various cell types [9][10][11][12][13][14]. Prilocaine was found to induce apoptosis in mouse and human osteoblastic cells [11] and lidocaine was shown to inhibit the proliferation of normal human fibroblasts, endothelial cells and keratinocytes [12], while enhancing bleomycin A 2 cytotoxicity and DNA strand breakage in murine leukemia cells and human head and neck carcinoma cells [13] and imparing corneal wound healing [14]. Dibucaine was shown to induce apoptosis in a neuroblastoma cell line [9] and in HL-60 [10] cells through activation of various caspases in conjunction with the release of cytochrome c from mitochondria induced by a processed product of Bid and depolarization of the mitochondrial membrane potential [10].…”

“…There are relatively fewer in vitro studies investigating the effects of local anesthetics on cell proliferation, apoptosis and gene expression [9][10][11][12][13][14]. It was reported that ropivacaine was shown to inhibit the proliferation of nontransformed cultured adult human fibroblasts, endothelial cells, keratinocytes [12] and primary rat fibroblast [6], as well as that of the transformed monkey kidney Vero cells [6] and human colon cell lines [15].…”

“…It was reported that ropivacaine was shown to inhibit the proliferation of nontransformed cultured adult human fibroblasts, endothelial cells, keratinocytes [12] and primary rat fibroblast [6], as well as that of the transformed monkey kidney Vero cells [6] and human colon cell lines [15]. Despite these studies, however, little is known about the mechanisms and signaling pathways through which ropivacaine inhibits cell proliferation or if, under certain conditions, induces apoptosis and alters gene expression.…”