Curcumin enhances the response of non-Hodgkin’s lymphoma cells to ionizing radiation through further induction of cell cycle arrest at the G2/M phase and inhibition of mTOR phosphorylation

Qiao, Qiao; Jiang, Yufei; Li, Guang

doi:10.3892/or.2012.2091

Cited by 31 publications

(28 citation statements)

References 40 publications

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“…Whether curcumin affected the post-translational modifications, such as phosphorylation, acetylation and ubiquitination, of either p53 or FOXO3a, thereby regulating their subcellular localization and transcriptional activities require further study. Consistent with this, other studies also found the link of curcumin and p53 or FOXO3a expression, and demonstrated the role of these transcription factors in mediating the effect of curcumin on controlling cell proliferation and other functions in other cell systems (27,28). We reasoned that more studies are required to explore the precise mechanism of p53 and FOXO3a expression, regulation and downstream pathways in mediating the overall response of curcumin.…”

Section: Discussionsupporting

confidence: 74%

“…The p53 and FOXO3a formed part of regulation transcriptional network to control cancer cell growth and apoptosis (33,34). In addition, curcumin induced expression of p53 or/and FOXO3a in inhibition of cancer cell growth and other functions have been shown in other cell systems (27,28,35,36). However, whether curcumin affects the interaction of these proteins to facilitate the inhibitory effect of NPC growth remain to be determined.…”

Section: Discussionmentioning

confidence: 86%

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Extracellular signal-regulated kinase signaling-mediated induction and interaction of FOXO3a and p53 contribute to the inhibition of nasopharyngeal carcinoma cell growth by curcumin

Tang

Zhao

et al. 2014

International Journal of Oncology

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Curcumin, one of the main bioactive components extracted from a traditional Chinese medicinal herb, exhibits potent anticancer activity against many types of cancer cells including nasopharyngeal carcinoma (NPC). However, the detailed molecular mechanism underlying this is not clearly understood. In this study, we showed that curcumin significantly inhibited the growth of NPC cells in a dose-and time-dependent manner as determined by MTT assays, while increasing apoptosis was also observed as measured by flow cytometry for the FITC-Annexin V and propidium iodide (PI) label and Hoechst 33258 staining. To further explore the potential mechanism, we showed that curcumin increased the phosphorylation of ERK1/2 but not p38 MAPK in a time-dependent manner, and induced protein expression of the tumor suppressors FOXO3a and p53 in a dose-dependent manner, which were not observed in the presence of PD98059, an inhibitor of ERK1/2. Furthermore, silencing of FOXO3a and p53 genes by siRNAs overcame the inhibitory effect of curcumin on cell proliferation. Silencing or blockade of p53 using siRNA or chemical inhibitor abrogated the effect of curcumin on expression of FOXO3a protein; silencing or overexpression of FOXO3a had no further effect on curcumin-induced p53 protein expression. Furthermore, blockade of ERK1/2 and exogenous expression of FOXO3a restored the effect of curcumin on growth of cells. Together, our studies show that curcumin inhibits growth and induces apoptosis of NPC cells through ERK1/2-mediated increase in the protein expression and interaction of p53 and FOXO3a. p53 is upstream of FOXO3a, which form a regulatory loop that mediates the effect of curcumin. This study unveils a new mechanism by which curcumin inhibits the proliferation and induces apoptosis of human NPC cells.

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Section: Discussionsupporting

confidence: 74%

Section: Discussionmentioning

confidence: 86%

Extracellular signal-regulated kinase signaling-mediated induction and interaction of FOXO3a and p53 contribute to the inhibition of nasopharyngeal carcinoma cell growth by curcumin

Tang

Zhao

et al. 2014

International Journal of Oncology

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“…Reverse transcription was performed using the M‐MLV reverse transcription reagent kit (Invitrogen, Carlsbad, CA, USA). Quantitative analyses of the mRNA expression levels of PERK and eIF2α were performed using the TaqMan analysis system (Applied Biosystems, Carlsbad, CA, USA) …”

Section: Methodsmentioning

confidence: 99%

Endoplasmic reticulum stress pathway PERK‐eIF2α confers radioresistance in oropharyngeal carcinoma by activating NF‐κB

et al. 2017

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Endoplasmic reticulum stress (ERS) plays an important role in the pathogenesis and development of malignant tumors, as well as in the regulation of radiochemoresistance and chemoresistance in many malignancies. ERS signaling pathway protein kinase RNA‐like endoplasmic reticulum kinase (PERK)‐eukaryotic initiation factor‐2 (eIF2α) may induce aberrant activation of nuclear factor‐κB (NF‐κB). Our previous study showed that NF‐κB conferred radioresistance in lymphoma cells. However, whether PERK‐eIF2α regulates radioresistance in oropharyngeal carcinoma through NF‐κB activation is unknown. Herein, we showed that PERK overexpression correlated with a poor prognosis for patients with oropharyngeal carcinoma (P < 0.01). Meanwhile, the percentage of the high expression level of PERK in oropharyngeal carcinoma patients resistant to radiation was higher than in patients sensitive to radiation (77.7 and 33.3%, respectively; P < 0.05). Silencing PERK and eIF2α increased the radiosensitivity in oropharyngeal carcinoma cells and increased radiation‐induced apoptosis and G2/M phase arrest. PERK‐eIF2α silencing also inhibited radiation‐induced NF‐κB phosphorylation and increased the DNA double strand break‐related proteins ATM phosphorylation. NF‐κB activator TNF‐α and the ATM inhibitor Ku55933 offset the regulatory effect of eIF2α on the expression of radiation‐induced cell apoptosis‐related proteins and the G2/M phase arrest‐related proteins. These data indicate that PERK regulates radioresistance in oropharyngeal carcinoma through NF‐kB activation‐mediated phosphorylation of eIF2α, enhancing X‐ray‐induced activation of DNA DSB repair, cell apoptosis inhibition and G2/M cell cycle arrest.

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“…63 It appears to do so by generating reactive oxygen species that upregulate repressors of Sp proteins ZBTB10 and ZBTB4 and downregulation of the microRNAs mir-20a, mir-27a, and mir-17-5p, which are regulators of these Sp repressors. Interestingly, curcumin is also showing promise as a sensitizing agent to ionizing radiation in Burkitt’s type lymphoma and non-Hodgkin lymphoma 64,65 and alone in its ability to reduce expression of multiple IAPs critical to chemoresistance in pancreatic cancer cell lines. 66 The natural agents resveratrol and quercetin in combination (RQ) have also shown a similar downregulation of Sp proteins and their targets, including surviving.…”

Section: Natural Agent Transcription Modulatorsmentioning

confidence: 99%

Yin Yang 1 (YY1): Regulation of Survivin and Its Role In Invasion and Metastasis

et al. 2017

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Despite significant clinical and basic science advancements, cancer remains a devastating disease that affects people of all ages, races, and backgrounds. The pathogenesis of cancer has recently been described to result from eight biological capabilities or hallmarks and two enabling characteristics. These eight hallmarks are: deregulation of cellular energetics, avoiding immune destruction, enabling replicative immortality, inducing angiogenesis, sustaining proliferative signaling, evading growth suppressors, resisting cell death, and activating invasion and metastasis. The enabling characteristics are: genome instability and mutation and tumor-promoting inflammation. Survivin, the fourth most common transcript found in cancer cells, is a protein that is thought to be involved in the enhanced proliferation, survival, and metastasis and possibly other key hallmarks of cancer cells. Understanding how this gene is turned on and off is vitally important for attempt improving cancer management and therapy. Our work has identified a novel transcriptional regulator of survivin called Yin Yang 1 (YY1), which has been observed to activate some gene promoters and repress others and is gaining increasing interest as a target of cancer therapy. Our work shows for the first time that YY1 represses survivin transcription by physically interacting with the survivin promoter. Furthermore, YY1 appears to contribute to basal survivin transcriptional activity, indicating that disruption of its binding may in part contribute to survivin overexpression after cellular stress events including chemotherapy and radiotherapy.

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Curcumin enhances the response of non-Hodgkin’s lymphoma cells to ionizing radiation through further induction of cell cycle arrest at the G2/M phase and inhibition of mTOR phosphorylation

Cited by 31 publications

References 40 publications

Extracellular signal-regulated kinase signaling-mediated induction and interaction of FOXO3a and p53 contribute to the inhibition of nasopharyngeal carcinoma cell growth by curcumin

Extracellular signal-regulated kinase signaling-mediated induction and interaction of FOXO3a and p53 contribute to the inhibition of nasopharyngeal carcinoma cell growth by curcumin

Endoplasmic reticulum stress pathway PERK‐eIF2α confers radioresistance in oropharyngeal carcinoma by activating NF‐κB

Yin Yang 1 (YY1): Regulation of Survivin and Its Role In Invasion and Metastasis

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