Antiproliferative activity of an angular furanocoumarin-oroselol in human oral cancer cells is mediated via autophagy induction, inhibition of cell migration, invasion, and downregulation of PI3K/AKT signalling pathway

Abstract

Oral carcinoma is a lethal type of cancer associated with huge morbidity and mortality. Oral cancer patients show a very low survival chances even if diagnosed at early stages. The need for novel naturally occurring chemotherapeutic drugs increases due to high cost and toxicity of currently used clinical drugs. Present study was designed to investigate anticancer property of oroselol, keeping in view the medicinal potential showed by coumarin subclass furanocoumarins. MTT assay and clonogenic assays were implemented for viability assessments. Transmission electron microscopy was used for autophagic studies. The transwell chambers assay was used to investigate the migration and invasion. Western blotting was performed to determine the expressions levels of autophagy and PI3K/AKT signalling related proteins. Results showed that oroselol could potentially inhibit viability of oral cancer SSC-4 cells in time- and dose-reliant fashion. The antiproliferative effects were mediated through autophagy induction as indicated by formation of autophagosomes and enhanced LC3-l expressions and reduced LC3-II and p62 expressions. Cancer cell migration and invasion was potentially supressed by oroselol cell treatment. The PI3K/AKT signalling pathway was blocked potentially by oroselol in SSC-4 cells which showed reduced phosphorylation of PI3K and AKT. In conclusion, oroselol holds a significant potential to induce autophagy-related antiproliferative effects along with inhibition of cell migration, cell invasion, and PI3K/AKT signalling pathway. Therefore, oroselol may prove to be a lead molecule in oral cancer chemotherapy provided further in vivo and toxicological studies are performed on it.