The anti-cancer efficacy of curcumin scrutinized through core signaling pathways in glioblastoma.
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 anti-glioblastoma drug through inhibition of the two core signaling pathways and promotion of the apoptotic pathway.
Su
Chin-Cheng
CC
Division of General Surgery, Buddhist Tzu Chi General Hospital, Hualien 97004, Taiwan, R.O.C.
Wang
Mei-Jen
MJ
Chiu
Tsung-Lang
TL
D000704:Analysis of Variance; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001399:Azure Stains; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects*; D003474:Curcumin / Q000494:pharmacology*; D005434:Flow Cytometry; D005909:Glioblastoma; D006801:Humans; D008853:Microscopy; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D000970:Antineoplastic Agents; D001399:Azure Stains; D016160:Retinoblastoma Protein; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D003474:Curcumin