Thalidomide distinctly affected TNF-α, IL-6 and MMP secretion by an ovarian cancer cell line (SKOV-3) and primary ovarian cancer cells

Abstract

Background. Thalidomide inhibits TNF-␣ production in lipopolysaccharide-stimulated monocytes. The aim of this study was to evaluate the effect of thalidomide on TNF-␣, IL-6 and MMP secretion in epithelial ovarian carcinoma cells. Materials and methods. SKOV-3 cells and primary epithelial ovarian carcinoma cells were cultured in the presence of various concentrations of thalidomide. Cell proliferation was examined by MTT proliferation assay. TNF-␣ and IL-6 levels were determined in the supernatants of the cell cultures by ELISA, and MMP activity was examined by gelatin zymography. Results. Thalidomide did not significantly affect the proliferation and growth of SKOV-3 cells. However, it decreased significantly the capacity of SKOV-3 cells and primary epithelial ovarian carcinoma cells to secrete TNF-␣. Thalidomide also significantly decreased the capacity of SKOV-3 cells, but not primary epithelial ovarian carcinoma cells, to secrete MMP-9 and MMP-2. However, thalidomide did not affect IL-6 secretion in SKOV-3 cells or primary epithelial ovarian carcinoma cells. Conclusion. Our study suggests that thalidomide distinctly affected TNF-␣, IL-6 and MMPs secretion by an ovarian carcinoma cell line (SKOV-3) and primary ovarian cancer cells. This might suggest a different susceptibility of these two types of cells to thalidomide, and/or that the mechanisms of secretion of the factors examined are differently regulated in these cells. Our results may deepen our understanding the mechanism/s of action of thalidomide in ovarian carcinoma cells. The results might have important implications in future therapeutic strategies that will incorporate thalidomide and other cytokine inhibitors in the treatment of epithelial ovarian carcinoma.

Substituted adamantylphthalimides: Synthesis, antiviral and antiproliferative activity

“…Thalidomide was almost inactive, which is in concordance with previous results. [ 18,22 ] Importantly, the growth of nontumor cell line HMEC‐1 was not affected by any treatment. Only compounds 5 and/or 9 minimally inhibited the growth of the tumor cell lines CEM and HeLa.…”

“…The experiments were carried out according to the previously published experimental procedure. [ 17,18,22 ] Briefly, the cells were seeded into standard 96‐well microtiter plates and left to attach for 24 hr. The next day, test compounds were added in five serial 10‐fold dilutions.…”

Preparation, characterization, in vitro and in vivo anti-tumor effect of thalidomide nanoparticles on lung cancer

“…Previous studies have shown that the anti-inflammatory, anti-angiogenic, and anti-tumor effects of THA may be due to its ability to block the production of TNF-α. 46 THA is thought to inhibit angiogenesis by reducing levels of VEGF as well as TNF-α. Ki 67, a cell nuclear antigen, is associated with cancer cell proliferation.…”

Involvement of peripheral TRPV1 channels in the analgesic effects of thalidomide

“…Moreover, there are reports and studies of thalidomide for the treatment of inflammatory and nociceptive pains as an analgesic or analgesic adjuvant in clinic due to its immunomodulatory and anti-inflammatory properties (Asher and Furnish, 2013;Belda et al, 1966;Chauhan et al, 2012;Ching et al, 2003;Peuckmann et al, 2003;Ribeiro et al, 2000;Schwartzman et al, 2003). Thalidomide can selectively suppress the production of tumor necrosis factor α (TNF-α) (Andrade et al, 2012;Klausner et al, 1996;Marriott, 1997;McHugh and Rowland, 1997;Piura et al, 2013;Schmidt et al, 1996), which plays a pivotal role in the generation of pains. TNF-α can induce the release of interleukin 1b and interleukin 6, which further stimulates the production of cyclo-oxygenase products as well as interleukin 8, a stimulant of the production of sympathomimetic mediators (Marriott, 1997;McHugh and Rowland, 1997;Piura et al, 2013).…”

“…Thalidomide can selectively suppress the production of tumor necrosis factor α (TNF-α) (Andrade et al, 2012;Klausner et al, 1996;Marriott, 1997;McHugh and Rowland, 1997;Piura et al, 2013;Schmidt et al, 1996), which plays a pivotal role in the generation of pains. TNF-α can induce the release of interleukin 1b and interleukin 6, which further stimulates the production of cyclo-oxygenase products as well as interleukin 8, a stimulant of the production of sympathomimetic mediators (Marriott, 1997;McHugh and Rowland, 1997;Piura et al, 2013). It was reported that thalidomide reduced both mechanical allodynia and thermal hyperalgesia in a mouse chronic constriction injury model of neuropathic pain.…”