Curcumin suppresses growth and chemoresistance of human glioblastoma cells via AP‐1 and NFκB transcription factors

Abstract

Malignant gliomas are a debilitating class of brain tumors that are resistant to radiation and chemotherapeutic drugs, contributing to the poor prognosis associated with these tumors. Over-expression of transcription factors such as NFjB and AP-1 contribute to the enhanced glioma survival, radioresistance, and chemoresistance. Curcumin, which may inhibit these pathways, was therefore investigated for a potential therapeutic role in glioma. The effect of curcumin on glioma survival was investigated in human (T98G, U87MG, and T67) and rat (C6) glioma cell lines. The ability of curcumin to overcome glioma cell radioresistance and chemoresistance was also explored. Curcumin reduced cell survival in a p53-and caspaseindependent manner, an effect correlated with the inhibition of AP-1 and NFjB signaling pathways via prevention of constitutive JNK and Akt activation. Curcumin-sensitized glioma cells to several clinically utilized chemotherapeutic agents (cisplatin, etoposide, camptothecin, and doxorubicin) and radiation, effects correlated with reduced expression of bcl-2 and IAP family members as well as DNA repair enzymes (MGMT, DNA-PK, Ku70, Ku80, and ERCC-1). These findings support a role for curcumin as an adjunct to traditional chemotherapy and radiation in the treatment of brain cancer.

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

“…Arrest of the cell cycle at the G2/M phase is one of the effects of curcumin found in this study, which is in agreement with our previous finding in breast cancer MDA-MB-231 cells, findings in human glioma U87 cells by Pratibha et al, and Liu et al in human glioma U251 cells (4,7,16). This event was considered to be derived from up-regulation of p53, which has been identified as a common target of curcumin in different cancers.…”

“…In malignant brain tumors, curcumin also exhibits its pleiotropic activity, which includes inducing cell cycle arrest at the G2/M stage through up-regulation of ING4, suppressing tumor growth by inhibition of AP-1 and NF-κB, and inhibiting anti-apoptotic signaling by increasing the Bax to Bcl-2 ratio (7)(8)(9). Nevertheless, most failure of cancer therapy in clinical practice is attributed to the polymorphism of cancer cells.…”

Curcumin Modulates Molecular Chaperones and Autophagy-Lysosomal Pathways In Vitro after Exposure to Aβ42

“…However, Cur at 10 μM concentration decreased the HSP90 level but the 1 μM concentration did not affect the HSP90 levels. The HSP90 level may have been reduced at 10 μM (Figure 2), because this concentration can induce neuronal death [46,47]. In our experiment, we observed that higher concentration (≤ 10 μM) induced neuronal apoptosis, whereas lower concentration especially nanomolar to 1 μM of Cur is neuroprotective.…”

“…In our experiment, we observed that higher concentration (≤ 10 μM) induced neuronal apoptosis, whereas lower concentration especially nanomolar to 1 μM of Cur is neuroprotective. It has been reported that higher concentration of Cur can induce neuronal apoptosis and act as an anti-cancer agent [46][47][48]. Although the mechanistic details of how Cur restored HSPs after Aβ42 exposure, or how they induce HSPs in SH-SY5Y cells, is still unclear to us, one possible explanation may be that Cur treatments confer neuroprotection by secreting several growth factors, including BDNF, NGF and IGF [49][50][51].…”

Apigenin enhances the cisplatin cytotoxic effect through p53-modulated apoptosis

“…Many tumors demonstrate good responsiveness to this drug, but drug resistance eventually develops, particularly in patients with lung, colorectal, prostate and ovarian cancer (22). Several approaches have been proposed to maintain cisplatin efficacy, including increased accumulation or stabilization of p53, upregulating reactive oxygen species production and inhibiting NF-κB and antiapoptotic proteins (23)(24)(25)(26). The current study investigated the effects of apigenin on p53 accumulation, and its effect on cisplatin Apigenin enhances the cisplatin cytotoxic effect through p53-modulated apoptosis or cisplatin (in PBS).…”