Characterization of in vivo Mammary and Prostate Tumor Xenograft Models for Growth and Response to Clinical Anticancer Agents

1999 ◽  
pp. 305-315 ◽  
Author(s):  
W. R. Waud ◽  
D. J. Dykes ◽  
M. G. Hollingshead ◽  
R. F. Camalier ◽  
P. S. Steeg ◽  
...  
Keyword(s):  
Anticancer Agents ◽  
Prostate Tumor ◽  
Tumor Xenograft ◽  
Xenograft Models

scholarly journals Novel Marine Compounds: Anticancer or Genotoxic?

2004 ◽  
Vol 2004 (2) ◽  
pp. 93-98 ◽  
Author(s):  
Jamal M. Arif ◽  
Amal A. Al-Hazzani ◽  
Muhammed Kunhi ◽  
Fahad Al-Khodairy
Keyword(s):  
Clinical Trials ◽  
Anticancer Agents ◽  
Screening Tests ◽  
Tumor Xenograft ◽  
Anticancer Compounds ◽  
Early Exit ◽  
Marine Compounds ◽  
Xenograft Models ◽  
Pharmaceutical Industries ◽  
Carcinogenesis Models

In the past several decades, marine organisms have generously gifted to the pharmaceutical industries numerous naturally bioactive compounds with antiviral, antibacterial, antimalarial, anti-inflammatory, antioxidant, and anticancer potentials. But till date only few anticancer drugs (cytarabine, vidarabine) have been commercially developed from marine compounds while several others are currently in different clinical trials. Majority of these compounds were tested in the tumor xenograft models, however, lack of anticancer potential data in the chemical- and/or oncogene-induced pre-initiation animal carcinogenesis models might have cost some of the marine anticancer compounds an early exit from the clinical trials. This review critically discusses importance of preclinical evaluation, failure of human clinical trials with certain potential anticancer agents, the screening tests used, and choice of biomarkers.

scholarly journals PGRMC1-dependent lipophagy promotes ferroptosis in paclitaxel-tolerant persister cancer cells

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Ji Hyeon You ◽  
Jaewang Lee ◽  
Jong-Lyel Roh
Keyword(s):  
Cancer Cells ◽  
Lipid Droplets ◽  
Tumor Xenograft ◽  
Acid Oxidation ◽  
Mouse Tumor ◽  
Autophagy Induction ◽  
Highly Sensitive ◽  
Xenograft Models

Abstract Background Progesterone receptor membrane component 1 (PGRMC1) is a heme-binding protein inducing dimerization with cytochrome P450, which mediates chemoresistance. Increased PGRMC1 expression is found in multiple types of resistant cancers, but the role of PGRMC1 in the ferroptosis of cancer cells remains unrevealed. Therefore, we examined the role of PGRMC1 in promoting ferroptosis in paclitaxel-tolerant persister cancer cells (PCC). Methods The effects of ferroptosis inducers and PGRMC1 gene silencing/overexpression were tested on head and neck cancer (HNC) cell lines and mouse tumor xenograft models. The results were analyzed about cell viability, death, lipid ROS and iron production, mRNA/protein expression and interaction, and lipid assays. Results PCC had more free fatty acids, lipid droplets, and fatty acid oxidation (FAO) than their parental cells. PCC was highly sensitive to inhibitors of system xc− cystine/glutamate antiporter (xCT), such as erastin, sulfasalazine, and cyst(e)ine deprivation, but less sensitive to (1S,3R)-RSL3. PGRMC1 silencing in PCC reduced ferroptosis sensitivity by xCT inhibitors, and PGRMC1 overexpression in parental cells increased ferroptosis by xCT inhibitors. Lipid droplets were degraded along with autophagy induction and autophagosome formation by erastin treatment in PCC. Lipophagy was accompanied by increased tubulin detyrosination, which was increased by SIRT1 activation but decreased by SIRT1 inhibition. FAO and lipophagy were also promoted by the interaction between lipid droplets and mitochondria. Conclusion PGRMC1 expression increased FAO and ferroptosis sensitivity from in vivo mice experiments. Our data suggest that PGRMC1 promotes ferroptosis by xCT inhibition in PCC.

scholarly journals Development of Novel Silyl Cyanocinnamic Acid Derivatives as Metabolic Plasticity Inhibitors for Cancer Treatment

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Grady L. Nelson ◽  
Conor T. Ronayne ◽  
Lucas N. Solano ◽  
Sravan K. Jonnalagadda ◽  
Shirisha Jonnalagadda ◽  
...  
Keyword(s):  
Cancer Cell ◽  
Anticancer Agents ◽  
Single Agent ◽  
Monocarboxylate Transporter ◽  
Tumor Xenograft ◽  
Anticancer Efficacy ◽  
Cell Proliferation Inhibition ◽  
Cyanocinnamic Acid

AbstractNovel silyl cyanocinnamic acid derivatives have been synthesized and evaluated as potential anticancer agents. In vitro studies reveal that lead derivatives 2a and 2b have enhanced cancer cell proliferation inhibition properties when compared to the parent monocarboxylate transporter (MCT) inhibitor cyano-hydroxycinnamic acid (CHC). Further, candidate compounds exhibit several-fold more potent MCT1 inhibition properties as determined by lactate-uptake studies, and these studies are supported by MCT homology modeling and computational inhibitor-docking studies. In vitro effects on glycolysis and mitochondrial metabolism also illustrate that the lead derivatives 2a and 2b lead to significant effects on both metabolic pathways. In vivo systemic toxicity and efficacy studies in colorectal cancer cell WiDr tumor xenograft demonstrate that candidate compounds are well tolerated and exhibit good single agent anticancer efficacy properties.

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