Abstract

A ginsenoside Rg1 is an active compound extracted from the stem and/or root of ginseng. Rg1 has been known to affect various human organ systems including the immune, cardiovascular, and nervous systems with its pharmacological effects. Timosaponin AIII (TA3) is a type of spirostanol saponins that are the major compounds of Anemarrhena asphodeloides. TA3 exerts anticancer effects in various human cancers, and the effects include attenuations of cancer cell migration and induction of apoptosis. In this study, I report that Rg1 drives the stimulation of TA3-induced cytotoxic effects in MG63 human osteosarcoma cells. Rg1 stimulates TA3-induced apoptosis in MG63 cells via selective intensification of caspase-3 activation. Rg1 and TA3 synergistically induced antimetastatic effects such as attenuation of MG63 cell migration and inhibitions of matrix metalloproteinases (MMP-2 and MMP-9). Rg1 and TA3 synergistically suppressed JNK, p38, ERK, β-catenin, and CREB signaling, which are key regulators of cancer metastasis. Finally, the synergistic anticancer effects of Rg1 and TA3 were also observed in U2OS human osteosarcoma cells, and this may indicate that the synergy is not limited specifically to MG63 cells. The results presented here suggest that the combinatorial use of Rg1 and TA3 may be a promising way to develop an effective antiosteosarcoma agent.

Highlights

  • Ginseng has been widely used as an effective herbal medicine in Northeast Asian countries

  • Among the various active components, ginsenosides are the representative phytochemicals that are attributable to the pharmacological effects of ginseng, anticancer activities [1]

  • To investigate the cytotoxic effect of Rg1 on MG63 human osteosarcoma cells, a Cell Counting Kit-8 (CCK-8) assay was performed. e cells were treated with ascending dosages of Rg1 (0, 100, 150, 200, 250, 300, and 400 μM). en, the cell viability was monitored by CCK-8 assay

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Summary

Introduction

Ginseng has been widely used as an effective herbal medicine in Northeast Asian countries. Among the various active components, ginsenosides are the representative phytochemicals that are attributable to the pharmacological effects of ginseng, anticancer activities [1]. Of various ginsenosides known so far, Rg1 is extracted from the ginseng root or stem (Figure 1(a)) [2, 3]. It is known to reduce apoptosis of nerve cells and mesenchymal stem cells [6, 7]. Among the various types of human cancers, osteosarcoma develops in the bone. It is one of the most aggressive cancers. Despite the efforts to develop effective antiosteosarcoma drugs, the survival rate has been continuously decreased so far [9]. Despite the efforts to develop effective antiosteosarcoma drugs, the survival rate has been continuously decreased so far [9]. is raises the necessity to develop a highly effective way of cure for human osteosarcoma

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