Corosolic acid (CRA), a triterpenoid named 2α-hydroxyursolic acid, is a natural compound derived from traditional Chinese medicinal herbs . CRA exists in various plants, including Schisandra chinensis, Lagerstroemia speciosa, Orthosiphon stamineus and Eriobotrya japonica . CRA has been reported to possess numerous biological activities, including anti-diabetic (, antioxidant , anti-atherosclerotic , cholesterol-reducing and anti-inflammatory , which suggested the potential therapeutic value of CRA. Previous studies have reported that CRA could suppresses the growth of various types of tumors, including glioblastoma , leukemia , gastric cancer and lung cancer . However, the effect of CRA on osteosarcoma remains unclear.
Osteosarcoma is the most common malignant primary bone tumor that occurs in children and adolescents, which comprises 20% of all bone tumors and ~5% of all pediatric tumors . The highest incidence of osteosarcoma appears in the second decade of life, implying an association between bone growth and tumor development . In recent years, due to multimodal therapeutic approaches combining high-dose chemotherapy, significant improvements in patient survival rates have been achieved . However, the overall relapse free-survival rate over 5 years has stagnated at 65-75% , being distant metastases the leading cause of mortality in osteosarcoma patients . Since chemotherapy is still the major therapeutic option for osteosarcoma, the exploration and development of more effective therapeutic agents is required.
Apoptosis, the major form of cell suicide, is critical to various physiological processes and to the maintenance of homeostasis in multicellular organisms . It is clear that apoptosis is critical for the cytotoxicity induced by anticancer drugs . Over the years, accumulating evidence has clearly indicated that anticancer drugs are able to induce apoptosis, and that this process is involved in the mediation of their cytotoxic effects . In addition, the selective regulation of the apoptotic pathway in cancer cells has been the goal of cancer researchers . However, the effect of CRA on the apoptosis of osteosarcoma cells remains unknown.
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