The anti-cancer efficacy of curcumin scrutinized through core signaling pathways in glioblastoma

Abstract

Abstract. Curcumin has been verified as an anti-cancer compound via multiple molecular targets. Its effective mechanisms include cell cycle arrest, inducing apoptosis, suppressing oncogenes, and enhancing tumor suppressor genes. The resistance of cells to chemotherapy, however, derives from the variable genetic aberration of cancer cells. Consequently, the core signaling pathways of glioblastoma have been explored to evaluate the efficacy of curcumin in proceeding through mutated genes in those pathways. In this study, the efficacy of curcumin was investigated in DBTRG cells. The cytotoxic ability was detected with MTT assay, and the influence of the cell cycle was checked with flow cytometry. The influence of the core signaling pathways was evaluated by Western blotting through the predominantly mutated proteins which included p53, p21, and cdc2 in the p53 pathway, CDKN2A/p16 and RB in the RB pathway, and EGFR, mTOR, Ras, PTEN, and Akt in the RTK-Ras-PI3K pathway. In addition, the apoptotic effect was determined by apoptosis-associated proteins Bcl-2, Bax, and caspase 3. Curcumin exhibits superior cytotoxicity on glioblastoma in a dose-and time-dependent manner in the MTT assay. In the core signaling pathways of glioblastoma, curcumin either significantly influences the p53 pathway by enhancing p53 and p21 and suppressing cdc2 or significantly inhibits the RB pathway by enhancing CDKN2A/p16 and suppressing phosphorylated RB. In the apoptotic pathway, the Bax and caspase 3 are significantly suppressed by curcumin and the Giemsa stain elucidates apoptotic features of DBTRG cells as well. In conclusion, curcumin appears to be an effective antiglioblastoma drug through inhibition of the two core signaling pathways and promotion of the apoptotic pathway.

Peer Review #1 of "Functional drug–target–disease network analysis of gene–phenotype connectivity for curcumin in hepatocellular carcinoma (v0.1)"

“…Debata et al reported that the sunitinib-curcumin combination was effective in restoring the tumor suppressor activity of the RB gene in renal cancer cells (Debata et al 2013). Furthermore, Su et al reported that curcumin significantly enhanced p53 or markedly inhibited the RB pathway by suppressing RB phosphorylation in the signaling pathways of glioblastoma (Su et al 2010). These studies demonstrated the anti-tumor activity of curcumin and prompted further investigation of curcumin in HCC.…”

Functional drug–target–disease network analysis of gene–phenotype connectivity for curcumin in hepatocellular carcinoma

“… Debata et al (2013) reported that the sunitinib-curcumin combination was effective in restoring the tumor suppressor activity of the RB gene in renal cancer cells. Furthermore, Su, Wang & Chiu (2010) reported that curcumin significantly enhanced p53 or markedly inhibited the RB pathway by suppressing RB phosphorylation in the signaling pathways of glioblastoma ( Su, Wang & Chiu, 2010 ). These studies demonstrated the anti-tumor activity of curcumin and prompted further investigation of curcumin in HCC.…”

ortho-Quinone tanshinones directly inhibit telomerase through an oxidative mechanism mediated by hydrogen peroxide

“…The results also add to the growing evidence that induction of ROS is a primary mechanism of Tan II-A biological activity. 3, 22 Given that the ROS induction we observed is directly related to the concentration of reducing equivalent DTT, we predict that the ability to generate ROS in cells may be similarly controlled by cellular redox environment, which may help to explain the pleiotropic effects of Tan II-A and other tanshinones. The cell-based assays reported here suggest that Tan II-A is cytotoxic to both telomerase-positive and telomerase-negative cells, but that telomerase-positive cell lines were more sensitive to Tan II-A than telomerase-negative cells.…”