Chemopreventive Effect of Oridonin on Oral Squamous Cell Carcinoma

Objectives: To evaluate the effect of oridonin on proliferation of oral squamous cell carcinoma (OSCC) cells, epidermal growth factor receptor (EGFR) protein levels and caspase-3 gene expression.

Methods: A molecular docking protocol was implemented using the CDOCKER protocol under the receptor ligand interaction protocol of Accelrys Discovery Studio 4.5. MTT assay was employed to determine the potentially cytotoxic IC50 value after a 48-hour treatment on SCC-15 (human tongue squamous cell carcinoma) cell line. The results were compared amongst the oridonin-treated, cetuximab-treated (a synthetic chemotherapeutic drug), combination therapy and untreated cells. Cell apoptosis was quantified using the polymerase chain reaction to evaluate caspase-3 gene expression. EGFR protein levels was measured using enzyme linked immunosorbent assay.
Results: Oridonin was docked inside the binding site of caspase-3 with protein data bank (PDB) code 6CKZ and EGFR with PDB code 1M17 with a binding energy score of -31.02 and -29.15, respectively. All treated groups showed proliferation inhibition, however the combination of oridonin and cetuximab exhibited the highest level of inhibition on cancer cell proliferation at an IC50 of 3.38μg/ml. The combination of oridonin and cetuximab induced significant apoptosis in the cancer cell line showing the highest median caspase-3 fold change of 20.75 compared to the other groups, which showed a relatively moderate apoptotic effect. SCC-15 cell line showed that the cells treated with oridonin yielded a lower expression of caspase-3 gene than cetuximab treated cells. All treated groups showed suppression of EGFR levels, the group treated with the dual therapy yielded better results.

Conclusions: Mixture of oridonin and cetuximab inhibited OSCC proliferation with the effect comparable to, or exceeding, that of cetuximab and oridonin alone. A combined oridonin-cetuximab mixture may be a potential additive mean in the treatment of OSCC.