Antitumor and antimigration effects of Salvia clandestina L. extract on osteosarcoma cells

Salvia clandestina L. is a wild perennial species present in the Salento area of Italy. Here, we examined the in vitro effects of an aqueous extract of S. clandestina L. on the MG-63 osteosarcoma cell line. The extract reduced osteosarcoma cell viability mainly by way of apoptosis, as we observed (1) upregulation of gene and protein expression of p53, cyclin-dependent kinase inhibitors p21^WAF1 and p27^Kip1 , and proapoptotic BAX; (2) activation of caspases; and (3) induction of a sub-G₁ peak in the cell cycle. The mitogen-activated protein kinases (MAPKs) JNK1/2 and p38 are activated and involved in the intracellular effects of the S. clandestina extract, as preincubation with the JNK1/2 inhibitor SP600125 or the p38 inhibitor SB203580 significantly decreased S. clandestina extract-induced cytotoxicity and inhibited increase in p53, p21^WAF1 , p27^Kip1 , and BAX. SP600125 also inhibited mRNA levels for all the aforementioned proteins, while SB203580 only affected p53 mRNA. Furthermore, S. clandestina extract treatment counteracted epithelial-to-mesenchymal transition, inhibited cell migration, and decreased the expression and activity of matrix metalloproteinase MMP2. In addition, S. clandestina extract enhanced the cytotoxic activity of cisplatin on MG-63 cells through downregulation of the Akt/PKB protein kinase. We conclude that S. clandestina extract may be a novel agent for osteosarcoma treatment.