Transformation of the naturally occurring frog skin peptide, alyteserin-2a into a potent, non-toxic anti-cancer agent

Amino Acids ◽  
2012 ◽  
Vol 44 (2) ◽  
pp. 715-723 ◽  
Author(s):  
J. Michael Conlon ◽  
Milena Mechkarska ◽  
Manju Prajeep ◽  
Kholoud Arafat ◽  
Milan Zaric ◽  
...  
Toxicon ◽  
2012 ◽  
Vol 60 (2) ◽  
pp. 107
Author(s):  
J. Michael Conlon ◽  
Milena Mechkarska ◽  
Kholoud Arafat ◽  
Samir Attoub

2013 ◽  
Vol 6 ◽  
pp. IJTR.S12094 ◽  
Author(s):  
Hollie E. Flick ◽  
Judith M. LaLonde ◽  
William P. Malachowski ◽  
Alexander J. Muller

β-lapachone is a naturally occurring 1,2-naphthoquinone-based compound that has been advanced into clinical trials based on its tumor-selective cytotoxic properties. Previously, we focused on the related 1,4-naphthoquinone pharmacophore as a basic core structure for developing a series of potent indoleamine 2,3-dioxygenase 1 (IDO1) enzyme inhibitors. In this study, we identified IDO1 inhibitory activity as a previously unrecognized attribute of the clinical candidate β-lapachone. Enzyme kinetics-based analysis of β-lapachone indicated an uncompetitive mode of inhibition, while computational modeling predicted binding within the IDO1 active site consistent with other naphthoquinone derivatives. Inhibition of IDO1 has previously been shown to breach the pathogenic tolerization that constrains the immune system from being able to mount an effective anti-tumor response. Thus, the finding that β-lapachone has IDO1 inhibitory activity adds a new dimension to its potential utility as an anti-cancer agent distinct from its cytotoxic properties, and suggests that a synergistic benefit can be achieved from its combined cytotoxic and immunologic effects.


2019 ◽  
Vol 18 (12) ◽  
pp. 1650-1655 ◽  
Author(s):  
Mohammad Saleem ◽  
Jawaria Asif ◽  
Muhammad Asif ◽  
Uzma Saleem

Background: Amygdalin is a cyanogenic glycoside which is described as a naturally occurring anticancer agent. Current review highlights apoptosis-inducing attributes of amygdalin towards different cancers and its potential application as an anti-cancer agent in cancer therapy. Method: Data about amygdalin was retrieved from all major scientific databases i.e., PubMed, ScienceDirect, Google Scholar, Scopus and Medline by using combination of keywords like amygdalin, apoptosis, laetrile, vitamin B- 17, pro-apoptotic proteins, anti-apoptotic proteins, hydrogen cyanide, mechanism of action of amygdalin and amygdalin therapy on humans. However, no specific time frame was followed for collection of data. Results: Data collected from already published articles revealed that apoptosis is a central process activated by amygdalin in cancer cells. It is suggested to stimulate apoptotic process by upregulating expression of Bax (proapoptotic protein) and caspase-3 and downregulating expression of Bcl-2 (anti-apoptotic protein). It also promotes arrest of cell cycle in G0/G1 phase and decrease number of cells entering S and G2/M phases. Thus, it is proposed to enhance deceleration of cell cycle by blocking cell proliferation and growth. Conclusion: The current review epitomizes published information and provides complete interpretations about all known anti-cancer mechanisms of amygdalin, possible role of naturally occurring amygdalin in fight against cancer and mistaken belief about cyanide toxicity causing potential of amygdalin. However, well-planned clinical trials are still needed to be conducted to prove effectiveness of this substance in vivo and to get approval for human use.


2019 ◽  
Author(s):  
B Bhattarai ◽  
SK Steffensen ◽  
PL Gregersen ◽  
JH Jensen ◽  
KD Sørensen ◽  
...  
Keyword(s):  

2020 ◽  
Vol 20 (8) ◽  
pp. 1017-1027
Author(s):  
Abdul M. Baig ◽  
Zohaib Rana ◽  
Mohammad M. Mannan ◽  
Areeba Khaleeq ◽  
Fizza Nazim ◽  
...  

Background: Targeting evolutionarily conserved proteins in malignant cells and the adapter proteins involved in signalling that generates from such proteins may play a cardinal role in the selection of anti-cancer drugs. Drugs targeting these proteins could be of importance in developing anti-cancer drugs. Objectives: We inferred that drugs like loperamide and promethazine that act as antagonists of proteins conserved in cancer cells like voltage-gated Calcium channels (Cav), Calmodulin (CaM) and drug efflux (ABCB1) pump may have the potential to be re-purposed as an anti-cancer agent in Prostate Cancer (PCa). Methods: Growth and cytotoxic assays were performed by selecting loperamide and promethazine to target Cav, CaM and drug efflux (ABCB1) pumps to elucidate their effects on androgen-independent PC3 and DU145 PCa cell lines. Results: We show that loperamide and promethazine in doses of 80-100μg/ml exert oncocidal effects when tested in DU145 and PC3 cell lines. Diphenhydramine, which shares its targets with promethazine, except the CaM, failed to exhibit oncocidal effects. Conclusion: Anti-cancer effects can be of significance if structural analogues of loperamide and promethazine that specifically target Cav, CaM and ABCB1 drug efflux pumps can be synthesized, or these two drugs could be re-purposed after human trials in PCa.


Author(s):  
Ana CarolinaSilveira Rabelo ◽  
Jéssica Borghesi ◽  
Ana Claudia O. Carreira ◽  
Rafael Gonçalves Hayashi ◽  
Fernanda Bessa ◽  
...  

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