Boldine, a natural aporphine alkaloid, inhibits telomerase at non-toxic concentrations

Chemico-biological Interactions
Sakineh Kazemi Noureini, Fatemeh Tanavar

Abstract

In a preliminary screening study of natural alkaloids, boldine, an aporphine alkaloid, showed an interesting dose and time dependent anti-proliferative effect in several cancer cell lines. Cytotoxicity of boldine in human fibroblasts was considerably lower than the telomerase positive embryonic kidney HEK293 and breast cancer MCF-7 and MDA-MB-231 cells. Whether boldine can inhibit telomerase was investigated here using a modified quantitative real-time telomere repeat amplification protocol (q-TRAP). This test showed that boldine inhibits telomerase in cells treated with sub-cytotoxic concentrations. Telomerase inhibition occurs via down-regulation of hTERT, the catalytic subunit of the enzyme. Boldine changed the splicing variants of hTERT towards shorter non-functional transcripts as well. A direct interaction of boldine with the enzyme may also be involved, though thermal FRET method did not detect any substantial interaction between boldine and synthetic telomere sequences. This study advocates boldine as a valuable candidate for telomerase-targeted cancer care. This study suggests that derivatives of boldine could be potent anti-cancer drugs.

References

Nov 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·R C AllsoppC B Harley
Apr 25, 1991·Nature·A M ZahlerD M Prescott
Jan 1, 1994·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·H Speisky, B K Cassels
Apr 1, 1997·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·J W Shay, S Bacchetti
Oct 3, 1999·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·L A CareyS Sukumar
Jan 27, 2000·Cell·D Hanahan, R A Weinberg
Sep 16, 2000·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Y Y JangC S Lee
Mar 27, 2001·International Journal of Cancer. Journal International Du Cancer·G A UlanerA R Hoffman
Mar 7, 2002·Parasitology International·N SriwilaijareonP Wilairat
Nov 27, 2002·Planta medica·C StévignyJ Quetin-Leclercq
Oct 2, 2003·International Journal of Cancer. Journal International Du Cancer·Norio IizukaKiwamu Okita
Mar 22, 2005·Current Medicinal Chemistry. Anti-cancer Agents·C StévignyJ Quetin-Leclercq
Oct 14, 2005·Chemico-biological Interactions·Peter O'BrienHernán Speisky
Dec 2, 2005·Breast Cancer Research and Treatment·Ginelle C GellertJerry W Shay
Feb 8, 2008·Nature Reviews. Cancer·Calvin B Harley
Dec 4, 2008·Investigational New Drugs·Daniéli GerhardtChristianne Salbego
Dec 10, 2009·Methods in Molecular Biology·Aurore GuédinJean-Louis Mergny
Aug 21, 2012·Asian Pacific Journal of Cancer Prevention : APJCP·Sakineh Kazemi Noureini, Michael Wink
Jun 20, 2014·Drug Design, Development and Therapy·Mohammadjavad PaydarMohd Rais Mustafa

❮ Previous
Next ❯

Citations

Apr 28, 2016·Pharmacology & Therapeutics·Yinnan Chen, Yanmin Zhang
Sep 11, 2016·Materials Science & Engineering. C, Materials for Biological Applications·Małgorzata Geszke-Moritz, Michał Moritz
Dec 22, 2017·International Journal of Molecular Sciences·Kumar Ganesan, Baojun Xu
Apr 20, 2018·International Journal of Molecular Sciences·Sakineh Kazemi NoureiniBruce Kennedy Cassels
Jul 31, 2019·Medicinal Research Reviews·Xing ChenXin-Hua Liu
May 12, 2020·Medicinal Research Reviews·Shalini BajajY C Mayur
Jan 2, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Esteban Rodríguez-ArceMarianela Saldías
Jan 17, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Muhammad Azizan SamadJamilah Syafawati Yaacob
May 10, 2017·Biochimica Et Biophysica Acta. General Subjects·Sakineh Kazemi NoureiniShozeb Haider

❮ Previous
Next ❯

Related Concepts

Related Feeds

Alternative splicing

Alternative splicing a regulated gene expression process that allows a single genetic sequence to code for multiple proteins. Here is that latest research.

Related Papers

Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry
Sakineh Kazemi Noureini, Michael Wink
Asian Pacific Journal of Cancer Prevention : APJCP
Sakineh Kazemi Noureini, Michael Wink
© 2022 Meta ULC. All rights reserved