Curcuminoids combined with gefitinib mediated apoptosis and autophagy of human oral cancer SAS cells in vitro and reduced tumor of SAS cell xenograft mice in vivo

Abstract

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.

Demethoxycurcumin Inhibits In Vivo Growth of Xenograft Tumors of Human Cervical Cancer Cells

“…In the present study, we found that DMC at 30 and 50 mg/kg significantly reduced tumor volume ( Figure 3) and tumor weight ( Figure 4C) without adverse effects on body weight of mice. This supports findings of Ni et al for the effects of another derivative of curcumin on subcutaneous xenograft tumors in human cervical HeLa cell-bearing mice in vivo (28,29). These findings are also in agreement with previous study on SAS human oral cancer cell xenografts in nude mice (29).…”

“…This supports findings of Ni et al for the effects of another derivative of curcumin on subcutaneous xenograft tumors in human cervical HeLa cell-bearing mice in vivo (28,29). These findings are also in agreement with previous study on SAS human oral cancer cell xenografts in nude mice (29). A decrease of body weight is an important marker in evaluating whether or not agents induce cytotoxic effects in vivo.…”

“…Previous study by our groups has indicated that DMC had potent anti-metastasis effects on HeLa cells in vitro (4). Recently, we also demonstrated that gefitinib combined with DMC treatment in nude mice bearing SAS human oral cancer cell xenografts significantly reduced the tumor weight and volume, and did not affect the total body weight (29). Co-treatment with DMC and temozolomide was shown to have synergistic activity in the induction of cell apoptosis and the inhibition of cell proliferation in glioblastoma multiforme cells (32).…”

Polyphenol-Mediated Autophagy in Cancer: Evidence of In Vitro and In Vivo Studies

“…In addition, the in vivo administration of gefitinib with curcumin, DMC or BDMC (30 mg/kg each, i.p., every two days) in SAS xenograft nude mice demonstrated that gefitinib co-administered with curcumin and DMC, but not with BDMC, induced a significant reduction in tumor growth in mice, compared to single treatments. Tumor tissue analysis showed the increased expression of caspase-6 and -7, associated with apoptosis, and of Beclin 1 and LC3, associated with autophagy, by the combination of gefitinib with curcuminoids [230]. The autophagic activation induced by the combined treatment of curcumin and gefitinib was also evaluated in gefitinib-resistant NSCLC cells H157 and H1299.…”

Tanshinone I induces cell apoptosis by reactive oxygen species-mediated endoplasmic reticulum stress and by suppressing p53/DRAM-mediated autophagy in human hepatocellular carcinoma

“…Accumulated evidence suggests that autophagy plays an important role in cell apoptosis mediated by anti-cancer drugs [9,10]. Furthermore, the p53/damage-regulated autophagy modulator (DRAM) signaling pathway has been reported to be involved in regulating autophagy [11,12].…”