AEE788 potentiates celecoxib-induced growth inhibition and apoptosis in human colon cancer cells

Venkatesan, G. K. D. Prasanna; Bhutia, Sujit K.; Singh, Abhay K.; Das, Swadesh K.; Dash, Rupesh; Chaudhury, Koel; Sarkar, Devanand; Fisher, Paul B.; Mandal, Mahitosh

doi:10.1016/j.lfs.2012.08.024

Cited by 13 publications

(9 citation statements)

References 46 publications

(84 reference statements)

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“…The scratch was made to create a wound across the monolayer cultured cells on 6‐well plates. After treatment, images of the scratches were taken at 0 and 24 h using a digital camera mounted on an inverted microscope (Olympus IX51) (Venkatesan et al, ). The wound healing was measured using the image analysis software program ProgRes® CapturePro 2.6.…”

Section: Methodsmentioning

confidence: 99%

Thymoquinone Restores Radiation‐Induced TGF‐β Expression and Abrogates EMT in Chemoradiotherapy of Breast Cancer Cells

Rajput

Kumar

Banik

et al. 2014

Journal Cellular Physiology

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Radiotherapy remains a prime approach to adjuvant therapies in patients with early and advanced breast cancer. In spite of therapeutic success, metastatic progression in patients undergoing therapy, limits its application. However, effective therapeutic strategies to understand the cellular and molecular machinery in inhibiting radiation-induced metastatic progression, which is poorly understood so far, need to be strengthened. Ionizing radiation was known to prompt cancer cell's metastatic ability by eliciting Transforming Growth Factor-beta (TGF-β), a key regulator in epithelial-mesenchymal transdifferentiation and radio-resistance. In this viewpoint, we employed thymoquinone as a radiosensitizer to investigate its migration and invasion reversal abilities in irradiated breast cancer cell lines by assessing their respective attributes. The role of metastasis regulatory molecules like TGF-β, E-cadherin, and integrin αV and its downstream molecules were determined using RT-PCR, western blotting, immunofluorescence, and extracellular TGF-β levels affirmed through ELISA assays. These studies affirmed the TGF-β restoring ability of thymoquinone in radiation-driven migration and invasion. Also, results demonstrated that the epithelial markers E-cadherin and cytokeratin 19 were downregulated whereas mesenchymal markers like integrin αV, MMP9, and MMP2 were upregulated by irradiation treatment; however thymoquinone pre-sensitization has reverted the expression of these proteins back to control proteins expression. Here, paclitaxel was chosen as an apoptosis inducer in TGF-β restored cells and confirmed its cytotoxic effects in radiation alone and thymoquinone sensitized irradiated cells. We conclude that this therapeutic modality is effective in preventing radiation-induced epithelial-mesenchymal transdifferentiation and concomitant induction of apoptosis in breast cancer.

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Section: Methodsmentioning

confidence: 99%

Thymoquinone Restores Radiation‐Induced TGF‐β Expression and Abrogates EMT in Chemoradiotherapy of Breast Cancer Cells

Rajput

Kumar

Banik

et al. 2014

Journal Cellular Physiology

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“…Electrophoresis was carried out at 4°C. The gel was washed with renaturation buffer (50 mM Tris–HCl, pH 7.5, 100 mM NaCl, and 2.5% Triton X-100), which was followed by incubation with a developing buffer (50 mM Tris–HCl, pH 7.5, 150 mM NaCl, 10 mM CaCl 2 , 0.02% NaN 3 , and 1 μM ZnCl 2 ) at 37°C for 16 h and staining with Coomassie Blue R-250, as described previously [27]. The stained bands are observed through a gel doc system (Bio-Rad).…”

Section: Methodsmentioning

confidence: 99%

Celecoxib alleviates tamoxifen-instigated angiogenic effects by ROS-dependent VEGF/VEGFR2 autocrine signaling

et al. 2013

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BackgroundTamoxifen (TAM) is widely used in the chemotherapy of breast cancer and as a preventive agent against recurrence after surgery. However, extended TAM administration for breast cancer induces increased VEGF levels in patients, promoting new blood vessel formation and thereby limiting its efficacy. Celecoxib (CXB), a selective COX-2 inhibitor, suppresses VEGF gene expression by targeting the VEGF promoter responsible for its inhibitory effect. For this study, we had selected CXB as non-steroidal anti-inflammatory drug in combination with TAM for suppressing VEGF expression and simultaneously reducing doses of both the drugs.MethodsThe effects of CXB combined with TAM were examined in two human breast cancer cell lines in culture, MCF7 and MDA-MB-231. Assays of proliferation, apoptosis, angiogenesis, metastasis, cell cycle distribution, and receptor signaling were performed.ResultsHere, we elucidated how the combination of TAM and CXB at nontoxic doses exerts anti-angiogenic effects by specifically targeting VEGF/VEGFR2 autocrine signaling through ROS generation. At the molecular level, TAM-CXB suppresses VHL-mediated HIF-1α activation, responsible for expression of COX-2, MMP-2 and VEGF. Besides low VEGF levels, TAM-CXB also suppresses VEGFR2 expression, confirmed through quantifying secreted VEGF levels, luciferase and RT-PCR studies. Interestingly, we observed that TAM-CXB was effective in blocking VEGFR2 promoter induced expression and further 2 fold decrease in VEGF levels was observed in combination than TAM alone in both cell lines. Secondly, TAM-CXB regulated VEGFR2 inhibits Src expression, responsible for tumor progression and metastasis. FACS and in vivo enzymatic studies showed significant increase in the reactive oxygen species upon TAM-CXB treatment.ConclusionsTaken together, our experimental results indicate that this additive combination shows promising outcome in anti-metastatic and apoptotic studies. In a line, our preclinical studies evidenced that this additive combination of TAM and CXB is a potential drug candidate for treatment of breast tumors expressing high levels of VEGF and VEGFR2. This ingenious combination might be a better tailored clinical regimen than TAM alone for breast cancer treatment.

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“…Apoptosis is a process of programmed cell death that is regulated by multiple intercellular and intracellular signals (18,19). Apoptosis is characterized by cell shrinkage, membrane blebbing, intracellular endonuclease activation, chromosomal DNA degradation, DNA fragmentation, nuclear/chromatin condensation, and formation of apoptotic bodies in cells (20,21). BAX is a pro-apoptotic protein on the outer mitochondrial membrane.…”

Section: Discussionmentioning

confidence: 99%

Treatment mechanism of matrine in combination with irinotecan for colon cancer

Duan

Deng

Da-bin³

et al. 2017

Oncology Letters

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The inhibitory effect of matrine (MA) was studied in combination with irinotecan (CPT-11) on proliferation of human colon carcinoma cell line HT29. We also explored the mechanism of cell apoptosis induction in HT29. HT29 cells were treated with different concentrations of MA and CPT-11 alone and in combination. The growth inhibition in HT29 cells was evaluated using MTT assay. Apoptosis was detected using AV-PI double staining flow cytometry. Transmission electron microscopy was used to detect structural changes in cells. Topoisomerase (TOPO) I, Bax and Caspase-3 expression levels were evaluated using western blot analysis. MA and CPT-11 alone and in combination, inhibited the proliferation of HT29 cells, whereas the combination treatment exhibited higher inhibitory effect (P<0.01). This suggests the existence of synergistic cytotoxicity. Compared with each treatment alone, the combination treatment caused more significant damage to cell structure, and caused a significantly higher apoptosis rate (P<0.01). Additionally, the combination treatment increased TOPO I, Bax and Caspase-3 expression levels (P<0.01). In conclusion, MA in combination with CPT-11 synergistically inhibited HT29 cell proliferation and induced apoptosis in these cells. The mechanism may be related to upregulation of the TOPO I, Bax and Caspase-3 protein expression.

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AEE788 potentiates celecoxib-induced growth inhibition and apoptosis in human colon cancer cells

Cited by 13 publications

References 46 publications

Thymoquinone Restores Radiation‐Induced TGF‐β Expression and Abrogates EMT in Chemoradiotherapy of Breast Cancer Cells

Thymoquinone Restores Radiation‐Induced TGF‐β Expression and Abrogates EMT in Chemoradiotherapy of Breast Cancer Cells

Celecoxib alleviates tamoxifen-instigated angiogenic effects by ROS-dependent VEGF/VEGFR2 autocrine signaling

Treatment mechanism of matrine in combination with irinotecan for colon cancer

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