Proscillaridin A induces apoptosis and inhibits the metastasis of osteosarcoma in vitro and in vivo

• Published in: Biochemical and biophysical research communications 2020-01, Vol.521 (4), p.880-886
• Main Authors: Fang, Shuo, Tao, Hai, Xia, Kezhou, Guo, Weichun
• Format: Article
• Language: English
• Subjects: Apoptosis; Osteosarcoma; Proliferation; Proscillaridin A; Tumor metastasis
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2019.11.012

The side effects of chemotherapy, drug resistance, and tumor metastasis hinder the development of treatment for osteosarcoma, leading to poor prognosis of patients with the disease. Proscillaridin A, a kind of cardiac glycoside, has been proven to have anti-proliferative properties in many malignant tumors, but the efficacy of the drug in treating osteosarcoma is unclear. In the present study, we assessed the effects of Proscillaridin A on osteosarcoma and investigated its underlying action mechanism. The cell cytotoxicity assay showed that Proscillaridin A significantly inhibited the proliferation of 143B cells in a dose- and time-dependent manner. Also, flow cytometry and invasion assay revealed that Proscillaridin A induced apoptosis and reduced 143B cell motility. Western blotting and PCR were used to detect the expressions of Bcl-xl and MMP2 and showed that mRNA/protein expression levels decreased significantly in Proscillaridin A-treated osteosarcoma cells. Using a mouse xenograft model, we found that Proscillaridin A treatment significantly inhibited tumor growth and lung metastasis in vivo and decreased the expression levels of Bcl-xl and MMP2. No noticeable side effect was observed in the liver, kidney, and hematological functions. Conclusively, Proscillaridin A suppressed proliferation, induced apoptosis, and inhibited 143B cell metastasis in vitro and in vivo, and these effects could be mediated by downregulating the expressions of Bcl-xl and MMP2. •Proscillaridin A inhibited osteosarcoma proliferation, induced apoptosis, and suppressed metastasis in vitro and in vivo.•Proscillaridin A inhibited osteosarcoma through Bcl-xl and MMP2.•Proscillaridin A had little toxicity on healthy cells and organs.