scholarly journals Folate metabolism: a re-emerging therapeutic target in haematological cancers

Leukemia ◽  
2021 ◽  
Author(s):  
Martha M. Zarou ◽  
Alexei Vazquez ◽  
G. Vignir Helgason
Keyword(s):  
Side Effects ◽  
De Novo ◽  
Therapeutic Strategies ◽  
Chemotherapeutic Agents ◽  
Cellular Level ◽  
Folate Metabolism ◽  
Methionine Cycle ◽  
Paediatric Leukaemia ◽  
Thymidylate Synthesis ◽  
New Chemotherapeutic Agents

AbstractFolate-mediated one carbon (1C) metabolism supports a series of processes that are essential for the cell. Through a number of interlinked reactions happening in the cytosol and mitochondria of the cell, folate metabolism contributes to de novo purine and thymidylate synthesis, to the methionine cycle and redox defence. Targeting the folate metabolism gave rise to modern chemotherapy, through the introduction of antifolates to treat paediatric leukaemia. Since then, antifolates, such as methotrexate and pralatrexate have been used to treat a series of blood cancers in clinic. However, traditional antifolates have many deleterious side effects in normal proliferating tissue, highlighting the urgent need for novel strategies to more selectively target 1C metabolism. Notably, mitochondrial 1C enzymes have been shown to be significantly upregulated in various cancers, making them attractive targets for the development of new chemotherapeutic agents. In this article, we present a detailed overview of folate-mediated 1C metabolism, its importance on cellular level and discuss how targeting folate metabolism has been exploited in blood cancers. Additionally, we explore possible therapeutic strategies that could overcome the limitations of traditional antifolates.

Side Effects and Good Effects from New Chemotherapeutic Agents

2005 ◽  
Vol 23 (10) ◽  
pp. 2425-2426 ◽  
Author(s):  
Masahiro Onozawa ◽  
Satoshi Hashino ◽  
Susumu Sogabe ◽  
Masahira Haneda ◽  
Hiromasa Horimoto ◽  
...  
Keyword(s):  
Side Effects ◽  
Chemotherapeutic Agents ◽  
New Chemotherapeutic Agents

Side Effects and Good Effects from New Chemotherapeutic Agents

2005 ◽  
Vol 23 (10) ◽  
pp. 2423-2424 ◽  
Author(s):  
Neil C. Nagaria ◽  
Janet Cogswell ◽  
Jin K. Choe ◽  
Basil Kasimis
Keyword(s):  
Side Effects ◽  
Chemotherapeutic Agents ◽  
New Chemotherapeutic Agents

scholarly journals The Effects ofN-Butyl-1-(4-dimethylamino)phenyl-1,2,3,4-tetrahydro-β-carboline-3-carboxamide againstLeishmania amazonensisAre Mediated by Mitochondrial Dysfunction

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Hélito Volpato ◽  
Vânia Cristina Desoti ◽  
Juliana Cogo ◽  
Manuela Ribeiro Panice ◽  
Maria Helena Sarragiotto ◽  
...  
Keyword(s):  
Side Effects ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Membrane ◽  
Membrane Integrity ◽  
Chemotherapeutic Agents ◽  
Superoxide Anions ◽  
High Toxicity ◽  
Cell Membrane Integrity ◽  
Mitochondrial Superoxide ◽  
New Chemotherapeutic Agents

Leishmaniasis is a disease that affects millions of people worldwide. The drugs that are available for the treatment of this infection exhibit high toxicity and various side effects. Several studies have focused on the development of new chemotherapeutic agents that are less toxic and more effective against trypanosomatids. We investigated the effects ofN-butyl-1-(4-dimethylamino)phenyl-1,2,3,4-tetrahydro-β-carboline-3-carboxamide (C4) and its possible targets againstL. amazonensis. The results showed morphological and ultrastructural alterations, depolarization of the mitochondrial membrane, the loss of cell membrane integrity, and an increase in the formation of mitochondrial superoxide anions inL. amazonensistreated withC4. Our results indicate thatC4is a selective antileishmanial agent, and its effects appear to be mediated by mitochondrial dysfunction.

Side Effects and Good Effects from New Chemotherapeutic Agents

2005 ◽  
Vol 23 (10) ◽  
pp. 2426-2428 ◽  
Author(s):  
C.S. Chim ◽  
G.C. Ooi ◽  
F. Loong ◽  
A.W.M. Au ◽  
A.K.W. Lie
Keyword(s):  
Side Effects ◽  
Chemotherapeutic Agents ◽  
New Chemotherapeutic Agents

Prostatic Acid Phosphatase (PAP) Differentiated Ultracytochemically from Lysosomal Acid Phosphate in the Rat with a PAP/Specific Substrate, Phosphorylcholine

1975 ◽  
Vol 33 ◽  
pp. 450-451
Author(s):  
W. Allen Shannon ◽  
José A. Serrano ◽  
Hannah L. Wasserkrug ◽  
Anna A. Serrano ◽  
Arnold M. Seligman
Keyword(s):  
Acid Phosphatase ◽  
Phosphate Buffer ◽  
Prostatic Carcinoma ◽  
Prostatic Acid Phosphatase ◽  
Chemotherapeutic Agents ◽  
Specific Substrate ◽  
Acid Phosphate ◽  
Lysosomal Acid ◽  
Design And Synthesis ◽  
New Chemotherapeutic Agents

During the design and synthesis of new chemotherapeutic agents for prostatic carcinoma based on phosphorylated agents which might be enzyme-activated to cytotoxicity, phosphorylcholine, [(CH3)3+NCH2CH2OPO3Ca]Cl-, has been indicated to be a very specific substrate for prostatic acid phosphatase (PAP). This phenomenon has led to the development of specific histochemical and ultracytochemical methods for PAP using modifications of the Gomori lead method for acid phosphatase. Comparative histochemical results in prostate and kidney of the rat have been published earlier with phosphorylcholine (PC) and β-glycerophosphate (βGP). We now report the ultracytochemical results.Minced tissues were fixed in 3% glutaraldehyde-0.1 M phosphate buffered (pH 7.4) for 1.5 hr and rinsed overnight in several changes of 0.05 M phosphate buffer (pH 7.0) containing 7.5% sucrose. Tissues were incubated 30 min to 2 hr in Gomori acid phosphatase medium (2) containing 0.1 M substrate, either PC or βGP.

Hybrid Compounds & Oxidative Stress Induced Apoptosis in Cancer Therapy

2020 ◽  
Vol 27 (13) ◽  
pp. 2118-2132 ◽  
Author(s):  
Aysegul Hanikoglu ◽  
Hakan Ozben ◽  
Ferhat Hanikoglu ◽  
Tomris Ozben
Keyword(s):  
Oxidative Stress ◽  
Drug Resistance ◽  
Side Effects ◽  
Cancer Therapy ◽  
Tumor Cells ◽  
Anticancer Drugs ◽  
Chemotherapeutic Agents ◽  
Oxidation Reactions ◽  
Hybrid Compounds ◽  
Induced Apoptosis

: Elevated Reactive Oxygen Species (ROS) generated by the conventional cancer therapies and the endogenous production of ROS have been observed in various types of cancers. In contrast to the harmful effects of oxidative stress in different pathologies other than cancer, ROS can speed anti-tumorigenic signaling and cause apoptosis of tumor cells via oxidative stress as demonstrated in several studies. The primary actions of antioxidants in cells are to provide a redox balance between reduction-oxidation reactions. Antioxidants in tumor cells can scavenge excess ROS, causing resistance to ROS induced apoptosis. Various chemotherapeutic drugs, in their clinical use, have evoked drug resistance and serious side effects. Consequently, drugs having single-targets are not able to provide an effective cancer therapy. Recently, developed hybrid anticancer drugs promise great therapeutic advantages due to their capacity to overcome the limitations encountered with conventional chemotherapeutic agents. Hybrid compounds have advantages in comparison to the single cancer drugs which have usually low solubility, adverse side effects, and drug resistance. This review addresses two important treatments strategies in cancer therapy: oxidative stress induced apoptosis and hybrid anticancer drugs.

SARS-CoV-2 Biology Insights, Part I. Genome-wide structure and druggability: literature review (Preprint)

2020 ◽  
Author(s):  
Laura Lafon-Hughes
Keyword(s):  
Side Effects ◽  
Literature Review ◽  
Host Cell ◽  
Nucleoside Analogs ◽  
Viral Proteins ◽  
Therapeutic Strategies ◽  
Adverse Side Effects ◽  
Viral Proteases ◽  
Genome Wide ◽  
Therapeutic Alternatives

BACKGROUND COVID-19 pandemic prompts the study of coronavirus biology and search of putative therapeutic strategies. OBJECTIVE To compare SARS-CoV-2 genome-wide structure and proteins with other coronaviruses, focusing on putative coronavirus-specific or SARS-CoV-2 specific therapeutic designs. METHODS The genome-wide structure of SARS-CoV-2 was compared to that of SARS and other coronaviruses in order to gain insights, doing a literature review through Google searches. RESULTS There are promising therapeutic alternatives. Host cell targets could be modulated to hamper viral replication, but targeting viral proteins directly would be a better therapeutic design, since fewer adverse side effects would be expected. CONCLUSIONS Therapeutic strategies (Figure 1) could include the modulation of host targets (PARPs, kinases) , competition with G-quadruplexes or nucleoside analogs to hamper RDRP. The nicest anti-CoV options include inhibitors of the conserved essential viral proteases and drugs that interfere ribosome slippage at the -1 PRF site.

Probiotics for the Chemoprotective Role Against the Toxic Effect of Cancer Chemotherapy

2021 ◽  
Vol 21 ◽  
Author(s):  
Aafrin Waziri ◽  
Charu Bharti ◽  
Mohammed Aslam ◽  
Parween Jamil ◽  
Aamir Mirza ◽  
...  
Keyword(s):  
Side Effects ◽  
Clinical Management ◽  
Clinical Evidence ◽  
Unmet Need ◽  
Chemotherapeutic Agents ◽  
Antitumor Effects ◽  
Anti Cancer ◽  
Different Types ◽  
Growth Promoting ◽  
High Degree

Background: The processes of chemo- and radiation therapy-based clinical management of different types of cancers are associated with toxicity and side effects of chemotherapeutic agents. So, there is always an unmet need to explore agents to reduce such risk factors. Among these, natural products have generated much attention because of their potent antioxidant and antitumor effects. In the past, some breakthrough outcomes established that various bacteria in the human intestinal gut are bearing growth-promoting attributes and suppressing the conversion of pro-carcinogens into carcinogens. Hence, probiotics integrated approaches are nowadays being explored as rationalized therapeutics in the clinical management of cancer. Methods: Here, published literature was explored to review chemoprotective roles of probiotics against toxic and side effects of chemotherapeutics. Results: Apart from excellent anti-cancer abilities, probiotics are bearing and alleviate toxicity and side effects of chemotherapeutics, with a high degree of safety and efficiency. Conclusion: Preclinical and clinical evidence suggested that due to the chemoprotective roles of probiotics against side effects and toxicity of chemotherapeutics, their integration in chemotherapy would be a judicious approach.

Bacterial origin of thymidylate and folate metabolism in Asgard Archaea

2021 ◽  
Author(s):  
Jonathan Filee ◽  
Hubert J. Becker ◽  
Lucille Mellottee ◽  
Zhihui LI ◽  
Jean-Christophe Lambry ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Lateral Gene Transfer ◽  
Phylogenetic Trees ◽  
De Novo ◽  
Horizontal Transmission ◽  
Folate Metabolism ◽  
Ecological Niches ◽  
Sequence Information ◽  
Amino Acid Utilization ◽  
Genome Wide

Little is known about the evolution and biosynthetic function of DNA precursor and the folate metabolism in the Asgard group of archaea. As Asgard occupy a key position in the archaeal and eukaryotic phylogenetic trees, we have exploited very recently emerged genome and metagenome sequence information to investigate these central metabolic pathways. Our genome-wide analyses revealed that the recently cultured Asgard archaeon Candidatus Prometheoarchaeum syntrophicum strain MK-D1 (Psyn) contains a complete folate-dependent network for the biosynthesis of DNA/RNA precursors, amino acids and syntrophic amino acid utilization. Altogether our experimental and computational data suggest that phylogenetic incongruences of functional folate-dependent enzymes from Asgard archaea reflect their persistent horizontal transmission from various bacterial groups, which has rewired the key metabolic reactions in an important and recently identified archaeal phylogenetic group. We also experimentally validated the functionality of the lateral gene transfer of Psyn thymidylate synthase ThyX. This enzyme uses bacterial-like folates efficiently and is inhibited by mycobacterial ThyX inhibitors. Our data raise the possibility that the thymidylate metabolism, required for de novo DNA synthesis, originated in bacteria and has been independently transferred to archaea and eukaryotes. In conclusion, our study has revealed that recent prevalent lateral gene transfer has markedly shaped the evolution of Asgard archaea by allowing them to adapt to specific ecological niches.

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