Oral squamous cell carcinoma (OSCC) is the most common malignant neoplasm with frequent metastasis and high mortality in the oral cavity. Plant-derived natural compounds are actively progressing as a trend for cancer treatment. Latifolin (Latif), is a natural flavonoid isolated from the heartwood of Dalbergia odorifera T. Chen (D. odorifera) has been known to have beneficial effects on anti-aging, anti-carcinogenic, anti-inflammatory, and cardio-protective activities. However, the anti-cancer effects of Latif are unknown in OSCC. Herein, as a result of analysis in terms of the aggressive features of OSCCs, we found that Latif significantly inhibited the cell proliferation of human YD-8 and YD-10B OSCCs, and caused the anti-metastatic activities by effectively blocking cell migration, invasion, and adhesion via the inactivation of focal adhesion kinase (FAK)/non-receptor tyrosine kinase (Src). Moreover, we found that Latif induced apoptotic cell death to suppress the cell survival and proliferation of YD-10B OSCCs by targeting PI3K/AKT/mTOR/p70S6K signaling. Finally, we analyzed in terms of autophagy and necroptosis, which are other mechanisms of programmed cell death and survival compared to apoptosis in YD-10B OSCCs. We found that Latif suppressed autophagic-related proteins and autophagosome formation, and also Latif inhibited necroptosis by dephosphorylating necroptosis-regulatory proteins (RIP1, RIP3, and MLKL). Given these findings, our results provided new evidence for Latif's biological effect and mechanism in YD-10B OSCCs, suggesting that Latif may be a new candidate for patients with OSCCs.
Keywords: D. odorifera; Latif; OSCCs; apoptosis; autophagy; necroptosis.