Leptocarpin Suppresses Proliferation, Migration, and Invasion of Human Osteosarcoma by Targeting Type-1 Insulin-Like Growth Factor Receptor (IGF-1R)

Abstract

BackgroundLeptocarpin (LTC) has drawn much attention for suppressing tumor growth or reducing inflammation. However, the effect of LTC on osteosarcoma has rarely been reported. Our object was to determine whether LTC suppresses MG63 cell proliferation, migration, and invasion, and whether type-1 insulin-like growth factor receptor (IGF-1R) is one of the targets in LTC suppressing osteosarcoma.Material/MethodsCytotoxicity of LTC was performed by use of a cell-counting kit-8 (CCK-8). RNA interference (RNAi) or pEABE-bleo IGF-1R plasmid were used for silencing or overexpressing IGF-1R, Western blot (WB) analysis was used for IGF-1R expression, CCK-8 for proliferation, and transwell assay for migration and invasion.ResultsLTC (23.533 μM) treatment for 48 h was taken as the 50% inhibiting concentration (IC50), which significantly (P<0.05) suppressed MG63 cells proliferation, migration, and invasion. LTC (IC50) obviously inhibited IGF-1R expression in MG63 cells, with similar effect to small interfering RNA (siRNA), while pEABE-bleo IGF-1R transfection overexpressed IGF-1R. siRNA silencing IGF-1R suppressed MG63 cells proliferation, migration, and invasion, while pEABE-bleo IGF-1R transfection was significantly (P<0.05) promoted. With or without siRNA or pEABE-bleo IGF-1R transfection, LTC (IC50) suppressed MG63 cells proliferation, migration, and invasion. The effect of LTC (IC50) combined with siRNA on suppressing MG63 cells proliferation, migration, and invasion was more obvious, while the effect of LTC (IC50) combined with pEABE-bleo IGF-1R transfection was less significant (P<0.05).ConclusionsLTC suppressed osteosarcoma proliferation, migration, and invasion by inhibiting IGF-1R expression. IGF-1R is one of the targets in LTC suppressing osteosarcoma.

Phytochemical Profiling and Assessment of Anticancer Activity of Leptocarpha rivularis Extracts Obtained from In Vitro Cultures

“…For cancer cells, negative absorbance values were measured, suggesting that a lethal level of LTC was reached, whereas for CoN cells and at the same LTC concentration only a decrease in their metabolic activity was observed. This result is in line with previous studies that have shown that LTC acts specifically on tumor cells of different origin [8,10,11]. Finally, treatment with the extract of clonal explants (T2, 12 ppm) induced a decrease in metabolism in both cell lines but without reaching lethal levels.…”

“…Previous phytochemical studies of L. rivularis have shown that extracts obtained from leaves, bark, and flowers exhibit antioxidant, hypoglycemic, and anticancer effects [3][4][5][6][7]. These biological activities have been attributed to the presence of sesquiterpene lactones, i.e., leptocarpine (LTC) as the major component and small amounts of rivularin and the 17,18-dihydroleptocarpin derivative [8][9][10][11]. It has also been described that LTC presents important cytotoxic effects on several cancer cell lines by inducing apoptosis [10], and inhibitory activity on specific growth factors in osteosarcoma [11].…”

Prognostic and Therapeutic Utility of Variably Expressed Cell Surface Receptors in Osteosarcoma

“…Both IR and IGF-1R have been investigated as therapeutic targets. A number of preclinical in vitro studies using OS cell lines have successfully suppressed cell proliferation, migration and invasion by inhibiting the IR/IGF-1R signaling pathway using miRNA, siRNA, and inhibitory antibodies [18,[21][22][23][24][25]. Kolb et al used R1507, an anti-IGF-1R antibody, in OS xenograft tumor models to delay tumor growth in 4 of 6 OS xenografts with significant improvement in EFS [26].…”