scholarly journals Quantification of Ultrasonic Scattering Properties of In Vivo Tumor Cell Death in Mouse Models of Breast Cancer

2015 ◽  
Vol 8 (6) ◽  
pp. 463-473 ◽  
Author(s):  
Hadi Tadayyon ◽  
Lakshmanan Sannachi ◽  
Ali Sadeghi-Naini ◽  
Azza Al-Mahrouki ◽  
William T. Tran ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Death ◽  
Tumor Cell ◽  
Mouse Models ◽  
Tumor Cell Death ◽  
Ultrasonic Scattering

scholarly journals Dominant-negative ATF5 rapidly depletes survivin in tumor cells

2019 ◽  
Vol 10 (10) ◽  
Author(s):  
Xiaotian Sun ◽  
James M. Angelastro ◽  
David Merino ◽  
Qing Zhou ◽  
Markus D. Siegelin ◽  
...  
Keyword(s):  
Cell Death ◽  
Tumor Cell ◽  
Cancer Cells ◽  
Dominant Negative ◽  
Tumor Cell Death ◽  
Cell Penetrating ◽  
Selective Death ◽  
Tumor Types

Abstract Survivin (BIRC5, product of the BIRC5 gene) is highly expressed in many tumor types and has been widely identified as a potential target for cancer therapy. However, effective anti-survivin drugs remain to be developed. Here we report that both vector-delivered and cell-penetrating dominant-negative (dn) forms of the transcription factor ATF5 that promote selective death of cancer cells in vitro and in vivo cause survivin depletion in tumor cell lines of varying origins. dn-ATF5 decreases levels of both survivin mRNA and protein. The depletion of survivin protein appears to be driven at least in part by enhanced proteasomal turnover and depletion of the deubiquitinase USP9X. Survivin loss is rapid and precedes the onset of cell death triggered by dn-ATF5. Although survivin downregulation is sufficient to drive tumor cell death, survivin over-expression does not rescue cancer cells from dn-ATF5-promoted apoptosis. This indicates that dn-ATF5 kills malignant cells by multiple mechanisms that include, but are not limited to, survivin depletion. Cell-penetrating forms of dn-ATF5 are currently being developed for potential therapeutic use and the present findings suggest that they may pose an advantage over treatments that target only survivin.

Green tea polyphenols block the anticancer effects of bortezomib and other boronic acid–based proteasome inhibitors

Blood ◽  
2009 ◽  
Vol 113 (23) ◽  
pp. 5927-5937 ◽  
Author(s):  
Encouse B. Golden ◽  
Philip Y. Lam ◽  
Adel Kardosh ◽  
Kevin J. Gaffney ◽  
Enrique Cadenas ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Cell Death ◽  
Tumor Cell ◽  
Green Tea ◽  
Boronic Acid ◽  
Proteasome Inhibitors ◽  
Green Tea Polyphenols ◽  
Tumor Cell Death

Abstract The anticancer potency of green tea and its individual components is being intensely investigated, and some cancer patients already self-medicate with this “miracle herb” in hopes of augmenting the anticancer outcome of their chemotherapy. Bortezomib (BZM) is a proteasome inhibitor in clinical use for multiple myeloma. Here, we investigated whether the combination of these compounds would yield increased antitumor efficacy in multiple myeloma and glioblastoma cell lines in vitro and in vivo. Unexpectedly, we discovered that various green tea constituents, in particular (-)-epigallocatechin gallate (EGCG) and other polyphenols with 1,2-benzenediol moieties, effectively prevented tumor cell death induced by BZM in vitro and in vivo. This pronounced antagonistic function of EGCG was evident only with boronic acid–based proteasome inhibitors (BZM, MG-262, PS-IX), but not with several non–boronic acid proteasome inhibitors (MG-132, PS-I, nelfinavir). EGCG directly reacted with BZM and blocked its proteasome inhibitory function; as a consequence, BZM could not trigger endoplasmic reticulum stress or caspase-7 activation, and did not induce tumor cell death. Taken together, our results indicate that green tea polyphenols may have the potential to negate the therapeutic efficacy of BZM and suggest that consumption of green tea products may be contraindicated during cancer therapy with BZM.

miR-15a regulation of endothelial radiation sensitivity in colorectal cancer.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 709-709
Author(s):  
Shushan Rajesh Rana ◽  
Cristina Espinosa ◽  
Rebecca Ruhl ◽  
Latroy Robinson ◽  
Charles R. Thomas ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Death ◽  
Tumor Growth ◽  
Tumor Cell ◽  
Background Radiation ◽  
Acid Sphingomyelinase ◽  
High Dose ◽  
Tumor Cell Death ◽  
Caspase 1

709 Background: Radiation dose escalation causes significant changes within the tumor microenvironment (TME) to enhance tumor cell death including altered microRNA (miR) levels. Among endothelial miRs, we identified miR-15a exhibits dose dependent differential regulation. miR-15a targets a key determinant of endothelial cell (EC) radiosensitivity, acid sphingomyelinase (SMPD1), an enzyme that drives rapid EC apoptosis via enhanced ceramide production. In colorectal cancer (CRC) (n = 182 patients), high miR-15a is associated with worse 5-year progression free and overall survival. miR-15a also affects immune function by promoting a pro-inflammatory TME milieu. We hypothesized miR-15a inhibition will increase tumor cell death through preservation of EC SMPD1, enhancing endothelial apoptosis and inflammatory cytokine upregulation. Methods: Using TaqMan Human miR panels, miRs were profiled in human umbilical vein ECs (HUVECs) after single 2 vs 20 Gy treatment. miR-target prediction programs identified miRs targeting SMPD1. In vitro gain and loss of function studies were performed with miR transfections in HUVECs and CT26 CRC cells. CXCL10 expression was measured by qRT-PCR. Caspase 1 activation was measured by a luminescence based assay. A CT26 syngeneic CRC flank murine model was used for in vivo miR-15a inhibitor assessment administered via tail vein injection unencapsulated or encapsulated in vascular-targeted 7C1 nanoparticles. Results: Among miRs targeting SMPD1, miR-15a exhibited the greatest differential change in HUVECs 6h post-IR between low and high dose radiation. Lower dose was associated with higher miR-15a and vice versa. Further, miR-15a levels inversely correlated with SMPD1. Exogenous miR-15a significantly decreased SMPD1 mRNA and protein. miR-15a inhibition decreased proliferation in both HUVECs and CT26 cells and increased apoptosis when combined with radiation. miR-15a inhibition increased endothelial CXCL10 expression and caspase-1 activation. Both systemic and vascular-targeted miR-15a inhibitor significantly diminished tumor growth in vivo. Conclusions: Our data suggests inhibition of vascular miR-15a is sufficient to decrease tumor growth likely due to rescue of endothelial SMPD1.

Proteomic characterization of EL4 lymphoma-derived tumors upon chemotherapy treatment reveals potential roles for lysosomes and caspase-6 during tumor cell death in vivo

PROTEOMICS ◽  
2017 ◽  
Vol 17 (12) ◽  
pp. 1700060 ◽  
Author(s):  
David A. Kramer ◽  
Mohamed A. Eldeeb ◽  
Melinda Wuest ◽  
John Mercer ◽  
Richard P. Fahlman
Keyword(s):  
Cell Death ◽  
Tumor Cell ◽  
Chemotherapy Treatment ◽  
Tumor Cell Death ◽  
Caspase 6

scholarly journals Enhancement of Tumor Cell Death by Combining gef Gene Mediated Therapy and New 1,4-Benzoxazepin-2,6-Dichloropurine Derivatives in Breast Cancer Cells

2018 ◽  
Vol 9 ◽  
Author(s):  
Alberto Ramírez ◽  
Ana Conejo-García ◽  
Carmen Griñán-Lisón ◽  
Luisa C. López-Cara ◽  
Gema Jiménez ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Death ◽  
Tumor Cell ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Tumor Cell Death

Personalization of breast cancer chemotherapy using noninvasive imaging methods to detect tumor cell death responses

2014 ◽  
Vol 3 (1) ◽  
pp. 31-35 ◽  
Author(s):  
Lakshmanan Sannachi ◽  
Hadi Tadayyon ◽  
Ali Sadeghi-Naini ◽  
Michael C Kolios ◽  
Gregory Czarnota
Keyword(s):  
Breast Cancer ◽  
Cell Death ◽  
Tumor Cell ◽  
Cancer Chemotherapy ◽  
Noninvasive Imaging ◽  
Tumor Cell Death ◽  
Imaging Methods ◽  
Breast Cancer Chemotherapy
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