Modulation of Sonic hedgehog signaling and WW domain containing oxidoreductase WOX1 expression enhances radiosensitivity of human glioblastoma cells

Chiang, Ming-Fu; Chen, Hsin-Hong; Chi, Chih‐Wen; Sze, Chun I.; Hsu, Ming-Ling; Shieh, Hui-Ru; Lin, Chin–Ping; Tsai, Jui Chen; Chen, Yu-Jen

doi:10.1177/1535370214565989

Cited by 19 publications

(10 citation statements)

References 33 publications

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“…The use of an antibody to neutralize SHH ligands or a GLI1 silencing approach reversed this protective capability. In GBM, Shh signaling was activated upon IR treatment [ 147 ]. Additionally, cyclopamine treatment increased DNA DSB as indicated by the induction of H2AX, a histone family member that becomes phosphorylated upon DNA breaks.…”

Section: Introductionmentioning

confidence: 99%

Hedgehog signaling: modulation of cancer properies and tumor mircroenvironment

2016

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Cancer poses a serious health problem in society and is increasingly surpassing cardiovascular disease as the leading cause of mortality in the United States. Current therapeutic strategies for cancer are extreme and harsh to patients and often have limited success; the danger of cancer is intensified as it metastasizes to secondary locations such as lung, bone, and liver, posing a dire threat to patient treatment and survival. Hedgehog signaling is an important pathway for normal development. Initially identified in Drosophila, the vertebrate and mammalian equivalent of the pathway has been studied extensively for its role in cancer development and progression. As this pathway regulates key target genes involved in development, its action also allows for the modulation of the microenvironment to prepare a tumor-suitable niche by manipulating tumor cell growth, differentiation, and immune regulation, thus creating an enabling environment for progression and metastasis. In this review, we will summarize recent scientific discoveries reporting the impact of the Hedgehog signaling pathway on the tumor initiation process and metastatic cascade, shedding light on the ability of the tumor to take over a mechanism crucially intended for development and normal function.

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Section: Introductionmentioning

confidence: 99%

Hedgehog signaling: modulation of cancer properies and tumor mircroenvironment

2016

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“…Inhibition of SMO represents a promising strategy to overcome therapy resistance in HGG; the Smoothened inhibitor cyclopamine has been shown to induce radiosensitization in glioblastoma cells and Erismodegib, another SMO inhibitor, was capable of inhibiting self-renewal and EMT in glioblastoma initiating cells [ 211 , 212 ]. Additionally, chemical inhibition of the hedgehog pathway could sensitize glioma stem cells to temozolomide [ 213 ].…”

Section: External Initiation Of the Epithelial-to-mesenchymal Transitmentioning

confidence: 99%

Signaling pathways and mesenchymal transition in pediatric high-grade glioma

Meel

Schaper

Kaspers

et al. 2017

Cell. Mol. Life Sci.

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Pediatric high-grade gliomas (pHGG), including diffuse intrinsic pontine gliomas (DIPG), are the most lethal types of cancer in children. In recent years, it has become evident that these tumors are driven by epigenetic events, mainly mutations involving genes encoding Histone 3, setting them apart from their adult counterparts. These tumors are exceptionally resistant to chemotherapy and respond only temporarily to radiotherapy. Moreover, their delicate location and diffuse growth pattern make complete surgical resection impossible. In many other forms of cancer, chemo- and radioresistance, in combination with a diffuse, invasive phenotype, are associated with a transcriptional program termed the epithelial-to-mesenchymal transition (EMT). Activation of this program allows cancer cells to survive individually, invade surrounding tissues and metastasize. It also enables them to survive exposure to cytotoxic therapy, including chemotherapeutic drugs and radiation. We here suggest that EMT plays an important, yet poorly understood role in the biology and therapy resistance of pHGG and DIPG. This review summarizes the current knowledge on the major signal transduction pathways and transcription factors involved in the epithelial-to-mesenchymal transition in cancer in general and in pediatric HGG and DIPG in particular. Despite the fact that the mesenchymal transition has not yet been specifically studied in pHGG and DIPG, activation of pathways and high levels of transcription factors involved in EMT have been described. We conclude that the mesenchymal transition is likely to be an important element of the biology of pHGG and DIPG and warrants further investigation for the development of novel therapeutics.

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“…The biological activities of zerumbone include anti-inflammation, 14 antitumor, 15 - 17 antiproliferation, 18 and antiplatelet aggregation. 18 , 19 In a previous study, zerumbone was also found to enhance the radiosensitivity of WOX1-overexpressed U373MG and U87MG cells 22 by downregulating the Gli-1/B-cell lymphoma 2 (Bcl-2) pathway. In addition, it has been reported to act as a radiosensitizer by promoting ROS-mediated DNA damage.…”

Section: Discussionmentioning

confidence: 94%

Zerumbone Regulates DNA Repair Responding to Ionizing Radiation and Enhances Radiosensitivity of Human Prostatic Cancer Cells

et al. 2017

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Introduction. Radiation therapy using ionizing radiation is widely used for the treatment of prostate cancer. The intrinsic radiation sensitivity of cancer cells could be enhanced by modulating multiple factors including the capacity to repair DNA damage, especially double-strand breaks (DSBs). We aimed to examine the effect of zerumbone on radiation sensitivity and its protective effects against ionizing radiation–induced DSB in human prostate cancer cells. Materials and Methods. The human prostate cancer PC3 and DU145 cell lines were used. A colony formation assay was performed to analyze the radiation survival of cells. DNA histogram and generation of reactive oxygen species (ROS) were examined using flow cytometry. Western blotting was used to examine the expression of regulatory molecules related to DNA damage repair. Results. Pretreatment with zerumbone enhanced the radiation effect on prostate cancer cells. Zerumbone delayed the abrogation of radiation-induced expression of γ-H2AX, an indicator of DNA DSB. Zerumbone pretreatment markedly reduced ionizing radiation–induced upregulated expression of phosphorylated ATM (ataxia telangiectasia-mutated), which was partially reversed by the ATM agonist methyl methanesulfonate. Ionizing radiation augmented and zerumbone pretreatment reduced the expression of Jak2 and Stat3, which are involved in DNA damage repair signaling. No significant effect on the generation of ROS and expression of ATR was noted after zerumbone treatment. Conclusion: Zerumbone sensitized DU145 and PC3 prostatic cancer cells to ionizing radiation by modulating radiation-induced ATM activation during repair of DNA DSBs.

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Modulation of Sonic hedgehog signaling and WW domain containing oxidoreductase WOX1 expression enhances radiosensitivity of human glioblastoma cells

Cited by 19 publications

References 33 publications

Hedgehog signaling: modulation of cancer properies and tumor mircroenvironment

Hedgehog signaling: modulation of cancer properies and tumor mircroenvironment

Signaling pathways and mesenchymal transition in pediatric high-grade glioma

Zerumbone Regulates DNA Repair Responding to Ionizing Radiation and Enhances Radiosensitivity of Human Prostatic Cancer Cells

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