Resveratrol-Induced Apoptosis and Increased Radiosensitivity in CD133-Positive Cells Derived From Atypical Teratoid/Rhabdoid Tumor

Kao, Chung Lan; Huang, Pin I.; Tsai, Ping-Hsing; Tsai, Ming Long; Lo, Jeng‐Fan; Lee, Yi Yen; Chen, Yann Jang; Chen, Yi Wei; Chiou, Shih Hwa

doi:10.1016/j.ijrobp.2008.12.035

Cited by 63 publications

(58 citation statements)

References 36 publications

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“…26 Western Blot Assay The extraction of proteins from cells and Western blot analyses were performed as described previously. 27 Fifteen microliters of sample were boiled at 95 C for 5 minutes and separated by 10% sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The proteins were transferred to Hybond-enhanced chemiluminescence (ECL) nitrocellulose paper (Amersham, Arlington Heights, Ill) by using a wet-transfer system.…”

Section: Microarray Analysis and Bioinformaticsmentioning

confidence: 99%

“…The protocol for immunofluorescence staining has been described previously. 27 Briefly, an avidin-biotin complex method was used for immunofluorescence staining in the spheroid cells. Each slide was treated with antibodies for p-STAT3 and antihuman survivin (Cell Signaling Technology).…”

Section: Microarray Analysis and Bioinformaticsmentioning

confidence: 99%

“…The integrated optical density of green fluorescence intensity was captured and subsequently analyzed using Image Proþ software (Media Cybernetics, Silver Spring, Md). 27 …”

Section: In Vivo Analysis Of Tumor Growth and Metastasismentioning

confidence: 99%

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Cucurbitacin I inhibits tumorigenic ability and enhances radiochemosensitivity in nonsmall cell lung cancer‐derived CD133‐positive cells

Hsu¹,

Huang

Chang

et al. 2011

Cancer

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BACKGROUND: Signal transducer and activator of transcription 3 (STAT3) signaling reportedly promotes tumor malignancy and recurrence in nonsmall cell lung cancer (NSCLC). It was demonstrated previously that the STAT3 pathway maintains the tumorigenicity and therapeutic resistance of malignant tumors as well as cancer stem cells (CSCs). The objective of the current study was to investigate the effect of the strong STAT3 inhibitor, cucurbitacin I, in prominin-1 (CD133)-positive lung cancer cells. METHODS: CD133-positive and CD133-negative NSCLC-derived cells were isolated from 7 patients with NSCLC. CD133-positive NSCLC cells that were treated with or without cucurbitacin I were evaluated for their expression of phosphorylated STAT3 (p-STAT3), tumorigenicity, stemness properties, and resistance to chemotherapeutic drugs and ionizing radiation. RESULTS: Compared with parental or CD133-negative NSCLC cells, CD133-positive NSCLC cells had greater tumorigenicity, greater radioresistance, and higher expression of octamer-binding transcription factor 4 (Oct-4), Nanog homeobox, and sex-determining region Y, box 2 (Sox2) at high p-STAT3 levels. Cucurbitacin I treatment at 100 nM effectively abrogated STAT3 activation, tumorigenic capacity, sphere formation ability, radioresistance, and chemoresistance in CD133-positive NSCLC cells. Microarray data suggested that cucurbitacin I inhibited the stemness gene signature of CD133-positive NSCLC cells and facilitated the differentiation of CD133-positive NSCLC cells into CD133-negative NSCLC cells. It is noteworthy that 150 nM cucurbitacin I effectively blocked STAT3 signaling and downstream survival targets, such as B-cell chronic lymphocytic leukemia/lymphoma 2 (Bcl-2) and Bcl-2-like 1 (Bcl-xL) expression and induced apoptosis in CD133-positive NSCLC cells. Finally, xenotransplantation experiments revealed that cucurbitacin I plus radiotherapy or chemotherapeutic drugs significantly suppressed tumorigenesis and improved survival in NSCLC-CD133-positive-transplanted, immunocompromised mice. CONCLUSIONS: Targeting STAT3 signaling in CD133-positive NSCLC cells with cucurbitacin I suppressed CSC-like properties and enhanced chemoradiotherapy response. The potential of cucurbitacin I should be verified further in future anti-CSC therapy.

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Section: Microarray Analysis and Bioinformaticsmentioning

confidence: 99%

Section: Microarray Analysis and Bioinformaticsmentioning

confidence: 99%

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Cucurbitacin I inhibits tumorigenic ability and enhances radiochemosensitivity in nonsmall cell lung cancer‐derived CD133‐positive cells

Hsu¹,

Huang

Chang

et al. 2011

Cancer

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“…Nevertheless, the potential interactions of MET and bioactive dietary components with known antitumor activities for CRC prevention and treatment, and specifically in the context of targeting CSC, have not been delineated. The importance of the latter is underscored by recent reports that dietary factors including the soy isoflavone genistein (Gen) (Montales et al 2012;Rahal et al 2013), polyphenolic compounds present in blueberries (Montales et al 2012), curcumin (Kakarala et al 2010), and resveratrol (Kao et al 2009), all of which have been reported to possess anti-metabolic/anti-diabetic properties (Gilbert and Liu 2013;Valsecchi 2013;Yeh et al 2014;Rouse et al 2014), can inhibit expansion of basal stem-like mammary cells with tumorigenic potential.…”

Section: Introductionmentioning

confidence: 99%

Metformin and soybean-derived bioactive molecules attenuate the expansion of stem cell-like epithelial subpopulation and confer apoptotic sensitivity in human colon cancer cells

et al. 2015

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Colorectal cancer (CRC) is a disease whose genesis may include metabolic dysregulation. Cancer stem cells are attractive targets for therapeutic interventions since their aberrant expansion may underlie tumor initiation, progression, and recurrence. To investigate the actions of metabolic regulators on cancer stem cell-like cells (CSC) in CRC, we determined the effects of soybeanderived bioactive molecules and the anti-diabetes drug metformin (MET), alone and together, on the growth, survival, and frequency of CSC in human HCT116 cells. Effects of MET (60 lM) and soybean components genistein (Gen, 2 lM), lunasin (Lun, 2 lM), b-conglycinin (bcon, 3 lM), and glycinin (Gly, 3 lM) on HCT116 cell proliferation, apoptosis, and mRNA/protein expression and on the frequency of the CSC CD133 ? CD44 ? subpopulation by colonosphere assay and fluorescence-activated cell sorting/flow cytometry were evaluated. MET, Gen, and Lun, individually and together, inhibited HCT116 viability and colonosphere formation and, conversely, enhanced HCT116 apoptosis. Reductions in frequency of the CSC CD133 ? CD44 ? subpopulation with MET, Gen, and Lun were found to be associated with increased PTEN and reduced FASN expression. In cells under a hyperinsulinemic state mimicking metabolic dysregulation and without and with added PTEN-specific inhibitor SF1670, colonosphere formation and frequency of the CD133 ? CD44 ? subpopulation were decreased by MET, Lun and Gen, alone and when combined. Moreover, MET ? Lun ? Gen co-treatment increased the pro-apoptotic and CD133 ?-CD44 ? -inhibitory efficacy of 5-fluorouracil under hyperinsulinemic conditions. Results identify molecular networks shared by MET and bioavailable soy food components, which potentially may be harnessed to increase drug efficacy in diabetic and non-diabetic patients with CRC.

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“…For example, RSV has been shown to enhance the radiosensitivity of cancer cell lines to IR, [10][11][12][13] suggesting a possible clinical benefit to patients receiving radiotherapy. 11,[14][15][16] Conversely, some reports show that RSV has protective effects against IR-mediated oxidative stress in non-cancerous ©2 0 1 1 L a n d e s B i o s c i e n c e .…”

Section: Introductionmentioning

confidence: 99%

The effects of resveratrol and selected metabolites on the radiation and antioxidant response

Fabre

Saito

DeGraff

et al. 2011

Cancer Biology & Therapy

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Excess reactive oxygen species (ROS) generated from ionizing radiation (IR) or endogenous sources like cellular respiration and inflammation produce cytotoxic effects that can lead to carcinogenesis. Resveratrol (RSV), a polyphenol with antioxidant and anticarcinogenic capabilities, has shown promise as a potential radiation modifier. The present study focuses on examining the effects of RSV or RSV metabolites as a radiation modifier in normal tissue. RSV or a RSV metabolite, piceatannol (PIC) did not protect human lung fibroblasts (1522) from the radiation-induced cell killing. Likewise, neither RSV nor PIC afforded protection against lethal total body IR in C3H mice. Additional research has shown protection in cells against hydrogen peroxide when treated with RSV. Therefore, clonogenic survival was measured in 1522 cells with RSV and RSV metabolites. Only the RSV derivative, piceatannol (PIC), showed protection against hydrogen peroxide mediated cytotoxicity; whereas, RSV enhanced hydrogen peroxide sensitivity at a 50 µM concentration; the remaining metabolites evaluated had little to no effect on survival. PIC also showed enhancement to peroxide exposure at a higher concentration (150 µM). A potential mechanism for RSV-induced sensitivity to peroxides could be its ability to block 1522 cells in the S-phase, which is most sensitive to hydrogen peroxide treatment. In addition, both RSV and PIC can be oxidized to phenoxyl radicals and quinones, which may exert cytotoxic effects. These cytotoxic effects were abolished when HBED, a metal chelator, was added. Taken together RSV and many of its metabolic derivatives are not effective as chemical radioprotectors and should not be considered for clinical use.

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Resveratrol-Induced Apoptosis and Increased Radiosensitivity in CD133-Positive Cells Derived From Atypical Teratoid/Rhabdoid Tumor

Cited by 63 publications

References 36 publications

Cucurbitacin I inhibits tumorigenic ability and enhances radiochemosensitivity in nonsmall cell lung cancer‐derived CD133‐positive cells

Cucurbitacin I inhibits tumorigenic ability and enhances radiochemosensitivity in nonsmall cell lung cancer‐derived CD133‐positive cells

Metformin and soybean-derived bioactive molecules attenuate the expansion of stem cell-like epithelial subpopulation and confer apoptotic sensitivity in human colon cancer cells

The effects of resveratrol and selected metabolites on the radiation and antioxidant response

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