Mucoadhesive film containing α-mangostin shows potential role in oral cancer treatment

Background Oral cancer is often preceded by a mucosal lesion called an oral potentially malignant disorder (OPMD). Many plant-derived compounds are of value in medicine. The objectives of this study were to develop a soluble mucoadhesive film containing α-mangostin (α-MG), a compound extracted from the peel of mangosteen fruit, and determine its activities against oral cancer cells, against human papillomavirus type 16 (HPV-16) pseudovirus, and its anti-inflammatory properties. Methods A soluble mucoadhesive film containing α-MG was prepared. Oral squamous carcinoma cell line (SCC25), murine macrophage cells (RAW264.7), and human gingival fibroblast cell line were cultured. Anticancer activity and viability of SCC25 cells in response to α-MG film solution were determined by MTT assay. HPV-16 pseudovirus was constructed and effects of the film solution on attachment and post-attachment steps of the infection were investigated. Anti-inflammatory activity was assessed by nitric oxide (NO) inhibition. Fibroblast cell migration was determined by in vitro scratch assay. Results The soluble α-MG film showed cytotoxic effects on SCC25 cells in concentration > 125 µg/ml with IC50 of 152.5 µg/ml. Antiviral activity against HPV-16 pseudovirus was observed at attachment step, but not at post-attachment step. The film also possessed a strong anti-inflammatory effect and promoted wound healing without cytotoxicity. Conclusions Mucoadhesive film containing α-MG has a cytotoxic effect on oral squamous carcinoma cell line and an inhibitory effect on HPV-16 pseudovirus at attachment step. The α-MG film also shows a potent anti-inflammatory activity and enhances wound healing. Thus, the soluble α-MG film may have a potential role in treating oral cancer.

Novel Hybrids of Podophyllotoxin and Coumarin Inhibit the Growth and Migration of Human Oral Squamous Carcinoma Cells

Oral squamous cell carcinoma is the most common malignancy of oral tumor. In this study, two novel hybrids of podophyllotoxin and coumarin were designed using molecular hybridization strategy and synthesized. Pharmacological evaluation showed that the potent compound 12b inhibited the proliferation of three human oral squamous carcinoma cell lines with nanomolar IC50 values, as well as displayed less toxicity on normal cells. Mechanistic studies indicated that 12b triggered HSC-2 cell apoptosis, induced cell cycle arrest, and inhibited cell migration. Moreover, 12b could disturb the microtubule network via binding into the tubulin. It was noteworthy that induction of autophagy by 12b was associated with the upregulation of Beclin1, as well as LC3-II. Furthermore, 12b significantly stimulated the AMPK pathway and restrained the AKT/mTOR pathway in HSC-2 cells. These results indicated that compound 12b was a promising candidate for further investigation.