Osteosarcoma (OS), a severe malignant bone tumour, usually occurs in adolescents and children and has a poor prognosis. Asiatic acid (AA), an active component isolated from Centella asiatica (L.) Urb., exhibits appreciable anti-oxidant and anti-tumour activities. So far, the effects and underlying mechanisms of AA against OS have not been clarified. Here, we explored the anti-tumour effects of AA against human OS and the involved mechanism mediating its actions. To evaluate effects of AA on the cell proliferation of human OS cells, cell viability and colony formation assays were performed. Flow cytometry was used to evaluate apoptosis in OS cells exposed to AA and mitochondrial membrane potential. Western blotting and RT-PCR were applied to determine expression of the relevant proteins and their mRNA levels. Our explorations showed that AA inhibits proliferation of human OS cells in a concentration- and time-dependent manner, and induces apoptosis of OS cells by the intrinsic (mitochondrial) pathway. Importantly, we found that inhibition of the AA-induced phosphorylation of JAK2/STAT3 signalling molecules and the decrease in MCL-1 contributed to the anti-tumour efficacy of AA. Collectively, our results suggest that AA could evoke mitochondrial- induced apoptosis in human OS cells by suppression of the JAK2/STAT3 pathway and MCL-1 expression. These results strongly demonstrate that AA could be a potential anti-tumour agent for OS treatment.
This mini-review aims to introduce the association between Secretory clusterin/apolipoprotein J (sCLU) and diverse musculoskeletal diseases. A comprehensive review of the literature was performed to identify basic science and clinical studies, which implied the therapeutic and prognostic role of sCLU in diverse musculoskeletal diseases. sCLU is a multifunctional glycoprotein that is ubiquitously expressed in various tissues and is implicated in many pathophysiological processes. Dysregulated expression of sCLU had been reported to be assocaited with proliferative or apoptotic molecular processes and inflammatory responses, which participated in many pathophysiological processes such as degenerative musculoskeletal diseases including ischemic osteonecrosis, osteoarthritis (OA) and degenerative cervical myelopathy (spinal cord injury), neoplastic musculoskeletal diseases, inflammatory and autoimmune musculoskeletal diseases including Rheumatoid arthritis (RA), joint damage induced by Brucella abortus, Sjogren's syndrome, idiopathic inflammatory myopathies, muscle glucose metabolism, insulin sensitivity and traumatic musculoskeletal diseases. Recent findings of sCLU in these musculoskeletal diseases provides insights on the therapeutic and prognostic role of sCLU in these musculoskeletal diseases. sCLU may serve as a promising therapeutic target for ischemic osteonecrosis, OA and spinal cord injury as well as a potential prognostic biomarker for OA and RA. Moreover, sCLU could act as a prognostic biomarker for osteosarcoma (OS) and a promising therapeutic target for OS resistance. Although many studies support the potential therapeutic and prognostic role of sCLU in some inflammatory and autoimmune-mediated musculoskeletal diseases, more future researches are needed to explore the molecular pathogenic mechanism mediated by sCLU implied in these musculoskeletal diseases.