ginsenoside-rg3 and Cardiotoxicity

The most common cause of osteosarcoma (OS) death is lung metastasis. Currently, doxorubicin is the primary chemotherapy drug used to treat OS, however, it is not effective in inhibiting metastasis, and it has obvious cardiotoxicity. The anticancer activity of ginsenoside Rg3 has been demonstrated in a variety of malignant tumours. The aim of this study was to determine the potential role of ginsenoside Rg3 and doxorubicin in OS and the possible mechanism.. The potential synergistic effects of ginsenoside Rg3 and doxorubicin on human osteosarcoma cells 143B and U2OS, human umbilical vein endothelial cells, and mice receiving 143B xenografts and lung metastases were investigated.. Our study demonstrated that the combination of ginsenoside Rg3 and doxorubicin significantly inhibited cell proliferation, metastasis and angiogenesis in vitro. Mechanically, the anti-tumour activity of ginsenoside Rg3 and doxorubicin by modulating mTOR/HIF-1α/VEGF and EMT signalling pathways. Furthermore, ginsenoside Rg3 combined with doxorubicin inhibits tumour growth and lung metastasis in 143B-derived murine osteosarcoma models. More importantly, ginsenoside Rg3 can effectively ameliorate doxorubicin-induced weight loss and cardiotoxicity in mice.. Consequently, we concluded that the combination of ginsenoside Rg3 and doxorubicin displayed an evidently synergistic effect, which has the potential to be used as an effective and safe therapeutic approach for OS treatment.

Topics: Animals; Bone Neoplasms; Cardiotoxicity; Cell Line, Tumor; Cell Proliferation; Doxorubicin; Endothelial Cells; Ginsenosides; Humans; Lung Neoplasms; Mice; Osteosarcoma; TOR Serine-Threonine Kinases; Vascular Endothelial Growth Factor A

Doxorubicin (DOX) is one of the most effective chemotherapy agents used in the treatment of hematological and solid tumors, however, it causes dose-related cardiotoxicity that may lead to heart failure in patients. One of the major reasons was increased reactive oxygen species (ROS) production. Ginsenoside Rg3 (Rg3), was powerful free radical scavengers and possessed cardioprotective effects. Nevertheless, Rg3 has low aqueous solubility and oral bioavailability, limiting its effects. Herein, we encapsulated Rg3 through spontaneous self-assembly of Pluronic F127 to improve its solubility and oral bioavailability. Moreover, co-administering Rg3 in Pluronic F127 micelles with doxorubicin can mitigate the cardiotoxicity, with ameliorating mitochondrial and metabolic function, improving calcium handling, and decreasing ROS production. In addition, it can improve the anticancer efficacy of doxorubicin. Therefore, our study provides a rational strategy for further developing a potentially viable adjunct-supportive treatment for reducing toxicity and increasing efficiency on chemotherapy.

Topics: Animals; Antineoplastic Agents; Apoptosis; Cardiotoxicity; Doxorubicin; Drug Carriers; Female; Ginsenosides; Male; Mice; Mice, Inbred C57BL; Micelles; Myocytes, Cardiac; Poloxamer; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species

Adriamycin (ADM) is an antineoplastic agent that is effective against a wide range of cancers, but cardiac toxicity limits its clinical application. Ginsenoside Rg3 (Rg3), an anti-cancer active ingredient of Panax ginseng, was reported to have anti-oxidative, anti-apoptotic, and cardioprotective properties.. The current study aimed to investigate the possible protective effect of Rg3 against ADM-induced cardiotoxicity.. The activity of Rg3 to improve endothelial dysfunction was processed both in vivo and in vitro.. We investigated the cardioprotective effect of Rg3 on ADM treated rats by echocardiography. The endothelial dysfunction was assessed using an aortic ring assay. Cardiac microvascular endothelial cells were cultured to investigate the effects of Rg3 on ADM-treated cells.. Results showed that Rg3 could ameliorate the decrease in the ejection fraction and fractional shortening that was induced by ADM, and improve the left ventricular outflow. The aortic ring assay showed that Rg3 could partially recover the abnormal vascular function. In vitro studies showed that Rg3 could promote cell viability to attenuate ADM induced oxidative damage and apoptosis. This counteraction was achieved partially via activation of the Nrf2-ARE pathway through the activation of Akt.. These findings elucidated the potential of Rg3 as a promising reagent for treating ADM-induced cardiotoxicity in clinic.

Topics: Animals; Antibiotics, Antineoplastic; Antioxidant Response Elements; Antioxidants; Aorta; Apoptosis; Calcium Signaling; Cardiotonic Agents; Cardiotoxicity; Cells, Cultured; Doxorubicin; Endothelial Cells; Endothelium, Vascular; Ginsenosides; Male; NF-E2-Related Factor 2; Oxidative Stress; Panax; Proto-Oncogene Proteins c-akt; Rats; Rats, Sprague-Dawley; Up-Regulation; Ventricular Function, Left