Gefitinib has been used for
cancer patients and
curcumin (CUR),
demethoxycurcumin (DMC), or
bisdemethoxycurcumin (BDMC) also shown to induce
cancer cell apoptosis. However, no report shows the combination of
gefitinib with, CUR, DMC, or BDMC induce cell apoptosis and autophagy in human
oral cancer cells. In this study, we investigated the effects of
gefitinib with or without CUR, DMC, or BDMC co-treatment on the cell viability, apoptotic cell death, autophagy, mitochondria membrane potential (
MMP), and
caspase-3 activities by flow cytometry assay and autophagy by
acridine orange (AO) staining in human
oral cancer SAS cells. Results indicated that
gefitinib co-treated with CUR, DMC, or BDMC decreased total viable cell number through the induction of cell apoptosis and autophagy and decreased the levels of
MMP and increased
caspase-3 activities in SAS cells. Western blotting indicated that
gefitinib combined with CUR, DMC, or BDMC led to decrease Bcl-2
protein expression which is an antiapoptotic
protein and to increase ATG5,
Beclin 1, p62/SQSTM1, and LC3 expression that associated with cell autophagy in SAS cells.
Gefitinib combined with CUR and DMC led to significantly reduce the
tumor weights and volumes in SAS cell xenograft nude mice but did not affect the total
body weights. Based on those observations, we suggest that the combination of
gefitinib with CUR, DMC, and BDMC can be a potential
anticancer agent for human
oral cancer in future.