Lupeol evokes anticancer effects in oral squamous cell carcinoma by inhibiting oncogenic EGFR pathway

Abstract

Epidermal growth factor receptor (EGFR) pathway is overexpressed in head and neck cancer (HNC). Lupeol, a natural triterpene (phytosterol found in fruits, vegetables, etc.), has been reported to be effective against multiple cancer indications. Here we investigate the antitumor effects of Lupeol and underlying mechanism in oral cancer. Lupeol-induced antitumor response was evaluated in two oral squamous cell carcinoma (OSCC) cell lines (UPCI:SCC131 and UPCI:SCC084) by viability (MTT), proliferation, and colony formation assays. Lupeol-mediated induction of apoptosis was examined by caspase 3/7 assay and flow cytometry. Effect of Lupeol on EGFR in the presence or absence of EGF was delineated by Western blot. The mRNA stability assay was performed to check the role of Lupeol on COX-2 mRNA regulation. Lupeol inhibited proliferation of OSCC cells in vitro by inducing apoptosis 48 h post treatment. Ligand-induced phosphorylation of EGFR and subsequent activation of its downstream molecules such as protein kinase B (PKB or AKT), I kappa B (IκB), and nuclear factor kappa B (NF-κB) was also found to be, in part, suppressed. Interestingly, Lupeol suppressed expression of COX-2 at mRNA and protein level in a time-dependent manner. Primary explants from oral squamous cell carcinoma tissues further confirmed significant inhibition of proliferation (Ki67) in Lupeol-treated explants as compared to untreated control at 48 h. Together these data suggest that Lupeol may act as a potent inhibitor of the EGFR signaling in OSCC and therefore imply its role in triggering antitumor efficacy.

Suppression of EGFR/STAT3 activity by lupeol contributes to the induction of the apoptosis of human non‑small cell lung cancer cells

“…The novelty of this study is as follows: First, to the best of our knowledge, this is the first study to demonstrate a contribution of the EGFR/STAT3 axis to the lupeol-induced apoptosis of NSCLC cells. Although previous studies have reported that lupeol suppresses EGFR activity in several cancer cells, they usually identified AKT as a downstream target of EGFR (36,37). In our case, the phosphorylation levels of AKT, as well as the MAPK proteins, the main signaling mediators activated by EGFR, were even slightly increased by lupeol treatment (Fig.…”

“…The suppression of tumorigenesis, the induction of apoptosis, cell cycle regulation, chemosensitization and the enhancement of the cytotoxic function of natural killer cells have been reported as the mechanisms of the anticancer effects of lupeol (7,(29)(30)(31)(32)(33)(34)(35)(36)(37). Notably, lupeol has been shown to suppress EGFR activity in oral squamous cell carcinoma and gallbladder carcinoma (36,37). It has also been shown to inhibit the STAT3 signaling cascade in hepatocellular carcinoma cells (7).…”

Lupeol, a Pentacyclic Triterpene, Promotes Migration, Wound Closure, and Contractile Effect In Vitro: Possible Involvement of PI3K/Akt and p38/ERK/MAPK Pathways

“…A stock solution of lupeol (10 mg/mL) was prepared by dilution in dimethyl sulfoxide (DMSO) and alcohol. We defined as standard protocol for all treatments the final concentration of DMSO and alcohol 0.25 and 0.075%, respectively, which did not show cytotoxicity in previous reports [ 61 ].…”

Microarray gene expression profiling in colorectal (HCT116) and hepatocellular (HepG2) carcinoma cell lines treated withMelicope ptelefolialeaf extract reveals transcriptome profiles exhibiting anticancer activity

“…The present study shows that MP-HX exert anticancer activity by inducing gene expression changes in HCT116 and HepG2 cells that can promote antiproliferative or anticancer effect. Phytochemical compounds with anticancer properties which have been identified in MP include β-sitosterol, lupeol, oleanolic acid, kokusaginine and genistein ( Baskar et al, 2010 ; Rauth et al, 2016 ; Shaari et al, 2011 ; Tiwari, Brunton & CS, 2013 ; Li et al, 2016b ; Molnar et al, 2013 ). Further studies are warranted to identify the exact constituent(s) that is/are responsible for MP anticancer activity.…”