Targeting argininosuccinate synthetase negative melanomas using combination of arginine degrading enzyme and cisplatin

Oncotarget
Niramol SavarajLynn Feun

Abstract

Loss of argininosuccinate synthetase (ASS) expression in melanoma makes these tumor cells vulnerable to arginine deprivation. Pegylated arginine deiminase (ADI-PEG20) which degrades arginine to citrulline and ammonia has been used clinically and partial responses and stable disease have been noted with minimal toxicity. In order to improve the therapeutic efficacy of ADI-PEG20, we have combined ADI-PEG20 with a DNA damaging agent, cisplatin. We have shown that the combination of the two drugs together significantly improved the therapeutic efficacy when compared to ADI-PEG20 alone or cisplatin alone in 4 melanoma cell lines, regardless of their BRAF mutation. In-vivo study also exhibited the same effect as in-vitro with no added toxicity to either agent alone. The underlying mechanism is complex, but increased DNA damage upon arginine deprivation due to decreased DNA repair proteins, FANCD2, ATM, and CHK1/2 most likely leads to increased apoptosis. This action is further intensified by increased proapoptotic protein, NOXA, and decreased antiapoptotic proteins, SURVIVIN, BCL2 and XIAP. The autophagic process which protects cells from apoptosis upon ADI-PEG20 treatment also dampens upon cisplatin administration. Thus, the combina...Continue Reading

References

Sep 1, 1995·Japanese Journal of Cancer Research : Gann·H TakakuK Miyazaki
Oct 25, 2003·The Journal of Biological Chemistry·Chi-Hui Tang, Elizabeth A Grimm
Aug 18, 2004·Genes & Development·Paul R AndreassenToshiyasu Taniguchi
Jun 28, 2005·International Journal of Cancer. Journal International Du Cancer·Larisa L BelyanskayaUwe Zangemeister-Wittke
Jul 22, 2005·Molecular Cancer·Chunjing WuNiramol Savaraj
Oct 20, 2005·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Paolo A AsciertoTheodore F Logan
May 2, 2006·Molecular Cancer Therapeutics·Deborah ChirnomasAlan D D'Andrea
Jun 22, 2006·Expert Opinion on Investigational Drugs·Lynn Feun, Niramol Savaraj
Jan 5, 2007·Journal of Gastroenterology and Hepatology·Francesco IzzoBrent E Korba
Dec 6, 2007·BMC Biochemistry·Céline Jacquemont, Toshiyasu Taniguchi
Dec 18, 2007·Molecular Cell·J Wade Harper, Stephen J Elledge
Feb 8, 2008·Nature Reviews. Cancer·Thomas HelledayRicky A Sharma
May 14, 2008·Current Pharmaceutical Design·L FeunN Savaraj
Jul 22, 2008·Nitric Oxide : Biology and Chemistry·David A WinkCurtis C Harris
Jan 9, 2009·Nucleic Acids Research·Qiang FanPaul R Andreassen
Mar 11, 2010·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Andrew G SikoraWillem W Overwijk
Mar 17, 2010·Biochemical and Biophysical Research Communications·Min YouLynn Feun
May 13, 2010·Current Molecular Medicine·N SavarajL G Feun
Jul 4, 2012·Nucleic Acids Research·Archana SareenAlexandra Sobeck
Nov 29, 2012·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Zhen-Yu DingXiao-Feng Sun
Dec 20, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jenny WuJohn A Hartley
Jan 8, 2013·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Ryan J Sullivan, Keith T Flaherty
Jan 24, 2013·Cancer Letters·Mariusz L Hartman, Malgorzata Czyz
Jul 23, 2013·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Alexander M Menzies, Georgina V Long
Oct 12, 2014·Melanoma Research·Vaidehi AgrawalArthur E Frankel

❮ Previous
Next ❯

Citations

Apr 8, 2017·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Emma BeddowesPeter W Szlosarek
Dec 21, 2018·Recent Patents on Biotechnology·Mahboubeh ZareiYounes Ghasemi
Oct 22, 2020·Cell Death Discovery·Lynsey BurkeAlessandro Rufini
Feb 24, 2019·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Peter E HallPeter W Szlosarek
Jan 19, 2020·Translational Research : the Journal of Laboratory and Clinical Medicine·Giulia AgnelloScott W Rowlinson
Apr 25, 2021·Nature Communications·Chia-Lin ChenHsing-Jien Kung
Jul 25, 2021·Cancers·Chia-Lin ChenHsing-Jien Kung
Jul 25, 2021·International Journal of Molecular Sciences·Chunjing WuNiramol Savaraj
Jul 27, 2021·Cancer Chemotherapy and Pharmacology·Neha Kumari, Saurabh Bansal

❮ Previous
Next ❯

Methods Mentioned

BETA
xenograft
immunoprecipitation
Assay
Protein Assay

Clinical Trials Mentioned

NCT01665183

Software Mentioned

ImageJ
CFlow Plus
Illumina Bead Studio

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

BCL-2 Family Proteins

BLC-2 family proteins are a group that share the same homologous BH domain. They play many different roles including pro-survival signals, mitochondria-mediated apoptosis and removal or damaged cells. They are often regulated by phosphorylation, affecting their catalytic activity. Here is the latest research on BCL-2 family proteins.

Ataxia telangiectasia (MDS)

Ataxia telangiectasia is a rare neurodegenerative diseases caused by defects in the ATM gene, which is involved in DNA damage recognition and repair pathways. Here is the latest research on this autosomal recessive disease.