title: 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.
authors.affiliation: Department of Signal Transduction and Biogenic Amines, Chittaranjan National Cancer Institute, 37 - S.P Mukherjee Road, Kolkata, 700026, India.
authors.forename: Sanchita
authors.initials: S
authors.lastname: Rauth
authors.affiliation: Department of Signal Transduction and Biogenic Amines, Chittaranjan National Cancer Institute, 37 - S.P Mukherjee Road, Kolkata, 700026, India.
authors.forename: Sudipta
authors.initials: S
authors.lastname: Ray
authors.affiliation: Department of Signal Transduction and Biogenic Amines, Chittaranjan National Cancer Institute, 37 - S.P Mukherjee Road, Kolkata, 700026, India.
authors.forename: Sayantan
authors.initials: S
authors.lastname: Bhattacharyya
authors.affiliation: Department of Molecular Pathology, Mitra Biotech, Narayana Nethralaya, Narayana Health City, Hosur Main Road, Bangalore, 560099, India.
authors.forename: Debapriya Ghosh
authors.initials: DG
authors.lastname: Mehrotra
authors.affiliation: Department of Surgical Oncology, Chittaranjan National Cancer Institute, 37 - S.P Mukherjee Road, Kolkata, 700026, India.
authors.forename: Neyaz
authors.initials: N
authors.lastname: Alam
authors.affiliation: Department of Pathology, Chittaranjan National Cancer Institute, 37 - S.P Mukherjee Road, Kolkata, 700026, India.
authors.forename: Goutam
authors.initials: G
authors.lastname: Mondal
authors.affiliation: Department of Medical Oncology, Chittaranjan National Cancer Institute, 37 - S.P Mukherjee Road, Kolkata, 700026, India.
authors.forename: Partha
authors.initials: P
authors.lastname: Nath
authors.affiliation: Department of Pathology & Cancer Screening, Chittaranjan National Cancer Institute, 37 - S.P Mukherjee Road, Kolkata, 700026, India.
authors.forename: Asoke
authors.initials: A
authors.lastname: Roy
authors.affiliation: Department of Translation Research, Chittaranjan National Cancer Institute, 37 - S.P Mukherjee Road, Kolkata, 700026, India.
authors.forename: Jaydip
authors.initials: J
authors.lastname: Biswas
authors.affiliation: Department of Signal Transduction and Biogenic Amines, Chittaranjan National Cancer Institute, 37 - S.P Mukherjee Road, Kolkata, 700026, India. nabendu.murmu@cnci.org.in.
authors.forename: Nabendu
authors.initials: N
authors.lastname: Murmu
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D066246:ErbB Receptors / Q000378:metabolism*; D006801:Humans; D009062:Mouth Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009363:Neoplasm Proteins / Q000378:metabolism*; D053978:Pentacyclic Triterpenes / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D000094042:Lupanes
chemical_list: D066246:ErbB Receptors; D009363:Neoplasm Proteins; D053978:Pentacyclic Triterpenes; C512478:EGFR protein, human; C010480:lupeol; D000094042:Lupanes
keywords: COX-2; EGFR; Lupeol; Oral squamous cell carcinoma