SIRT1 and osteosarcoma: For example, melatonin has been shown to inhibit the expression of SIRT1, a pro-oncogenic gene product responsible for the downregulation of p53-mediated apoptosis implicated in multiple human cancers, including osteosarcoma, prostate adenocarcinoma, and retinoid orphan nuclear receptor alpha (RORα) gene-associated breast cancer [105,106].