Anticancer effects of 6-shogaol via the AKT signaling pathway in oral squamous cell carcinoma

Abstract

Anticancer effects of 6-shogaol via the AKT signaling pathway in oral squamous cell carcinoma Objective: Oral squamous cell carcinoma (OSCC) is one of the common type of cancer that leads to death; and is becoming a global concern.Due to the lack of efficient chemotherapeutic agents for patients with oral cancer, the prognosis remains poor. 6-shogaol, a bioactive compound of ginger, has a broad spectrum of bioactivities and has been widely used to relieve many diseases. However, its effects on human oral cancer have not yet been fully evaluated. In our study, we investigated the anticancer effects of 6-shogaol on the proliferation, migration, invasion, apoptosis, and underlying mechanisms within human OSCC cell lines. Methodology:We investigated the effect of 6-shogaol on the growth of OSCC cells by cell viability and soft agar colony formation assay. Migration and invasion assays were conducted to confirm the effect 6-shogaol on OSCC cell metastasis.Apoptosis was detected by flow cytometry and the underlying mechanism on the antigrowth effect of 6-shogaol in OSCC cells was assessed using western blotting. Results: In our results, 6-shogaol not only suppressed proliferation and anchorage-independent cell growth in OSCC cells, but also induced apoptosis by regulating the apoptosis-associated factors such as p53, Bax, Bcl-2, and cleaved caspase-3. Migration and invasion of OSCC cells were inhibited following the regulation of E-cadherin and N-cadherin by 6-shogaol. Additionally, 6-shogaol treatment significantly inhibited the PI3K/AKT signaling pathway. Conclusion: Therefore, our results may provide critical evidence that 6-shogaol can be a potential new therapeutic candidate for oral cancer.

Anticancer perspective of 6-shogaol: anticancer properties, mechanism of action, synergism and delivery system

“…Acute lymphoid leukemia Nalm-6 cells induced massive apoptosis after 6-shogaol intervention and upregulation of p53 was found to mediate the onset of apoptosis [ 60 ]. In the oral squamous cell carcinoma model, 6-shogaol induced cancer cell apoptosis by inhibiting the PI3K/AKT/mTOR signaling pathway [ 44 ]. In a hepatocellular carcinoma model, 6-shogaol induced apoptosis by inhibiting the AKT/mTOR/MRP1 pathway, thus exhibiting apoptotic phenomena such as smaller nuclei, condensation of chromatin around the nuclear membrane, and rupture of the nucleus [ 15 , 61 ].…”

“…Epithelial-mesenchymal transition (EMT) is a process by which epithelial cells acquire an extreme ability to migrate and invade, a process that is closely related to tumor metastasis, invasion, and chemoresistance [ 80 ]. In oral cancer OSCC cell lines, 6-shogaol at a concentration of 8 μM inhibited the migration and invasion of 60% of cancer cells, which was found to be related to the downregulation of EMT related proteins by 6-shogaol, including E-cadherin and N-cadherin [ 44 ]. In breast cancer models, 6-shogaol was shown to attenuate the expression of the EMT marker gene Vimentin.…”

“…This finding was also confirmed in a study of 6-shogaol on oral squamous cell carcinoma cell lines (OSCC). p53, Bax and cleaved caspase-3 expression were significantly increased in 6-shogaol-treated OSCC cells, while Bcl-2 expression was attenuated, ultimately causing apoptosis in OSCC cells [ 44 ]. Furthermore, Uddin et al found that 6-shogaol promoted apoptosis by increasing TRAIL-mediated p53 protein expression in a combination regimen of 6-shogaol and TRAIL [ 88 ].…”

“…In oral squamous cell carcinoma, 6-shogaol binds directly to Akt as a ligand, thereby blocking this signaling. Subsequently, the expression of p-PI3K, p-AKT, p-mTOR and GSK3β, a molecule downstream of Akt, was downregulated in a dose-dependent manner, inducing massive apoptosis [ 44 ]. In cervical, 6-shogaol triggers the mitochondrial apoptotic pathway by inhibiting the PI3K/Akt/mTOR signaling.…”

6-Shogaol Exhibits a Promoting Effect with Tax via Binding HSP60 in Non-Small-Cell Lung Cancer

“…Recently, 6-SH has been reported to exert anti-tumor properties in cervical cancer, leukemia, oral squamous carcinoma, etc. [ 11 , 12 , 13 , 14 ], and it can suppress the proliferation of NSCLC cells [ 15 ], but the mechanism and target proteins remain unknown.…”