Crebanine Induces Apoptotic Cell Death in Human Oral Cancer KB Cells via Upregulating Pro-apoptotic Markers and Downregulating JAK2/STAT3 Pathway

Background Oral squamous cell carcinoma (OSCC) signifies a major global health issue, defined by its destructive nature and often delayed diagnosis, leading to suboptimal prognoses. The global case and mortality rates of OSCC continue to increase, especially among younger populations. Purpose This work aims to study the anti-cancer properties of crebanine on oral cancer KB cells by inducing apoptosis via suppressing PI3K/AKT/mTOR and JAK-2/STAT-3 pathways. Materials and Methods Crebanine at various doses (0.5–25 µM) was evaluated for its in vitro free-radical scavenging properties, including 2,2-diphenyl-1-picrylhydrazyl (DPPH), peroxyl, and superoxide radicals. The impact of crebanine on the growth of oral cancer KB and normal Vero cells was evaluated with a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test. The mitochondrial membrane potential (MMP) level in untreated and crebanine-treated KB cells was assessed using a fluorescent staining assay. The oxidative stress markers, apoptosis-related proteins, and PI3K/AKT/mTOR and JAK-2/STAT-3 pathway proteins were evaluated in untreated and crebanine-treated KB cells. Results The findings of the free radical scavenging experiments demonstrated the in vitro anti-oxidant properties of crebanine. The findings of the MTT experiment revealed that crebanine considerably inhibited the viability of KB cells without significantly affecting the normal Vero cells. The crebanine treatment reduced the MMP level in KB cells, as demonstrated by the findings of the fluorescent staining assay. The crebanine-treated KB cells exhibited elevated thiobarbituric acid reactive substances (TBARS) levels, alongside decreased glutathione (GSH) and superoxide dismutase (SOD) levels. Furthermore, crebanine treatment enhanced the pro-apoptotic proteins Bax and caspase-3/9 levels, while concurrently inhibiting the PI3K/AKT/mTOR and JAK-2/STAT-3 signaling protein levels in KB cells. Conclusion The current study demonstrates that crebanine treatment can impede cellular proliferation, trigger oxidative stress, and facilitate apoptosis in KB cells via downregulating PI3K/AKT/mTOR and JAK-2/STAT-3 pathways.