Cephaeline Disrupts Cancer Stem Cell Pathways to Enhance Chemotherapy Response in Oral Squamous Cell Carcinoma Cells

Background/Aim: This study aimed to investigate the effects of cephaeline on oral squamous cell carcinoma (OSCC) cell lines, with a focus on cancer stem cell (CSC) regulation and its interaction with cisplatin. Materials and Methods: The SCC4, SCC9, and SCC25 cell lines were utilized. Cell viability was assessed using the MTT assay, while CSC content was evaluated using the tumorsphere formation assay and the aldehyde dehydrogenase enzymatic activity assay. Tumorsphere formation was monitored daily, and aldehyde dehydrogenase activity was measured by flow cytometry. Immunofluorescence staining was conducted to assess histone acetylation status (H3K9ac) and NFκB signaling. Additionally, the combined impact of cephaeline and cisplatin on OSCC cells was assessed through the MTT assay. Results: Cisplatin treatment did not significantly affect tumorsphere formation, whereas a single dose of cephaeline disrupted tumorsphere formation in SCC4 and SCC9 and reduced the population of aldehyde dehydrogenase-positive cells. Cephaeline also inhibited the NFκB pathway and increased H3 histone acetylation levels. Notably, cephaeline sensitized OSCC cells to cisplatin. Conclusion: Cephaeline is a promising therapeutic agent for OSCC by disrupting CSC populations through NFκB inhibition and histone H3 acetylation. This study is the first to demonstrate that combining cephaeline with cisplatin could serve as a potential treatment strategy for oral cancer.