Arginine deiminase expressed <i>in vivo</i>, driven by human telomerase reverse transcriptase promoter, displays high hepatoma targeting and oncolytic efficiency

Jiang, Huiling; Guo, Song; Xiao, Dan; Bian, Xuzhao; Wang, Jie; Wang, Ying; Zhou, Huiting; Cai, Jin; Zheng, Zhaohui

doi:10.18632/oncotarget.17032

Cited by 15 publications

(15 citation statements)

References 38 publications

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“…In colon cancer cells, administration of arginine deiminase causes a p53-dependent cell cycle arrest by induction of microRNA-16 [ 309 ]. Finally, expression of arginine deiminase by a human telomerase reverse transcriptase promoter presented higher hepatoma targeting and oncolytic efficiency than expression of p53 by the same promoter in vivo [ 310 ].…”

Section: Therapy Targeting Metabolismmentioning

confidence: 99%

p53 and metabolism: from mechanism to therapeutics

et al. 2018

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The tumor cell changes itself and its microenvironment to adapt to different situations, including action of drugs and other agents targeting tumor control. Therefore, metabolism plays an important role in the activation of survival mechanisms to keep the cell proliferative potential. The Warburg effect directs the cellular metabolism towards an aerobic glycolytic pathway, despite the fact that it generates less adenosine triphosphate than oxidative phosphorylation; because it creates the building blocks necessary for cell proliferation. The transcription factor p53 is the master tumor suppressor; it binds to more than 4,000 sites in the genome and regulates the expression of more than 500 genes. Among these genes are important regulators of metabolism, affecting glucose, lipids and amino acids metabolism, oxidative phosphorylation, reactive oxygen species (ROS) generation and growth factors signaling. Wild-type and mutant p53 may have opposing effects in the expression of these metabolic genes. Therefore, depending on the p53 status of the cell, drugs that target metabolism may have different outcomes and metabolism may modulate drug resistance. Conversely, induction of p53 expression may regulate differently the tumor cell metabolism, inducing senescence, autophagy and apoptosis, which are dependent on the regulation of the PI3K/AKT/mTOR pathway and/or ROS induction. The interplay between p53 and metabolism is essential in the decision of cell fate and for cancer therapeutics.

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Section: Therapy Targeting Metabolismmentioning

confidence: 99%

p53 and metabolism: from mechanism to therapeutics

et al. 2018

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“…There are primarily two ways to induce arginine depletion. One is ADI, an enzyme obtained from mycoplasma that catabolizes arginine to citrulline and ammonia and has been reported to have a powerful antitumor effect in ASS1‐deficient cancers including HCC, prostate cancer, melanoma, and leukemia . Another is rhArg, an enzyme that can degrade arginine to ornithine and urea and has shown anticancer activity in certain tumors .…”

Section: Introductionmentioning

confidence: 99%

“…One is ADI, an enzyme obtained from mycoplasma that catabolizes arginine to citrulline and ammonia and has been reported to have a powerful antitumor effect in ASS1-deficient cancers including HCC, prostate cancer, melanoma, and leukemia. [9][10][11][12] Another is rhArg, an enzyme that can degrade arginine to ornithine and urea and has shown anticancer activity in certain tumors. 13,14 Both of these agents are modified by PEG, which can reduce their immunogenicity and enhance bioavailability.…”

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confidence: 99%

Recombinant human arginase induces apoptosis through oxidative stress and cell cycle arrest in small cell lung cancer

Lam

Cheng³

et al. 2018

Cancer Science

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Small cell lung cancer (SCLC) accounts for approximately 13% of all lung cancer cases. Small cell lung cancer is characterized by frequent relapse, and current treatments lack tumor specificity. Arginine is a non‐essential amino acid for human normal cells but critical to some tumor cells that cannot synthesize arginine. Therefore, arginine deprivation has become a potential therapeutic option for selected tumors. BCT‐100 is a pegylated arginase that has documented anticancer activity in arginine auxotrophic tumors, such as melanoma, hepatocellular carcinoma, and acute myeloid leukemia. One of the resistance mechanisms to arginase treatment is overexpression of argininosuccinate synthetase (ASS1) and ornithine transcarbamylase (OTC), two important enzymes in the urea cycle. We selected 9 SCLC and 1 non‐small cell lung carcinoma cell lines to determine the growth inhibition effects of BCT‐100 and established that cell lines with low expression of ASS1 and OTC are relatively sensitive to BCT‐100 treatment. Knocking down OTC in a H841 cell line could potentiate its sensitivity to BCT‐100 treatment. Arginine concentration was sharply decreased, accompanied by apoptosis through oxidative stress as well as G1 cell cycle arrest. In addition, BCT‐100 showed an anticancer effect on H446 and H510A xenograft models by lowering arginine levels and inducing apoptosis.

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“…For this reason, sTRAIL has been extensively used in OAds [66,[87][88][89][90][91]. Different transgenes that induce late apoptosis have been reported [66,[92][93][94][95].…”

Section: Virocentric Transgenesmentioning

confidence: 99%

Effect of Transgene Location, Transcriptional Control Elements and Transgene Features in Armed Oncolytic Adenoviruses

Farrera-Sal

Fillat

Alemany

2020

Cancers

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Clinical results with oncolytic adenoviruses (OAds) used as antitumor monotherapies show limited efficacy. To increase OAd potency, transgenes have been inserted into their genome, a strategy known as "arming OAds". Here, we review different parameters that affect the outcome of armed OAds. Recombinant adenovirus used in gene therapy and vaccination have been the basis for the design of armed OAds. Hence, early region 1 (E1) and early region 3 (E3) have been the most commonly used transgene insertion sites, along with partially or complete E3 deletions. Besides transgene location and orientation, transcriptional control elements, transgene function, either virocentric or immunocentric, and even the codons encoding it, greatly impact on transgene levels and virus fitness.

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Arginine deiminase expressed in vivo, driven by human telomerase reverse transcriptase promoter, displays high hepatoma targeting and oncolytic efficiency

Cited by 15 publications

References 38 publications

p53 and metabolism: from mechanism to therapeutics

p53 and metabolism: from mechanism to therapeutics

Recombinant human arginase induces apoptosis through oxidative stress and cell cycle arrest in small cell lung cancer

Effect of Transgene Location, Transcriptional Control Elements and Transgene Features in Armed Oncolytic Adenoviruses

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