Chemopreventive activity of celastrol in drug-resistant human colon carcinoma cell cultures

Oncotarget
Helena MoreiraKazimierz Gąsiorowski

Abstract

Celastrol (tripterine) a pentacyclic triterpenoid extracted from the roots of Tripterygium wilfordii Hook f., exhibits potent antioxidant and anti-inflammatory activity and also exerts important anti-cancer effects, as induction of apoptosis and lowering the level of drug resistance of several cancers. Increased level of cellular resistance to cytostatic drugs is typical for colorectal cancers, and largely determines the failure of chemotherapy for this tumor. The purpose of our research was to evaluate the chemopreventive effect of celastrol on cultures of colon cancer cells resistant to doxorubicin (LOVO/DX). With the use of flow cytometry we have shown that celastrol reduces the cell size of the SP (side population; subpopulation of cancer cells enriched with cancer stem cells), increases frequency of apoptosis and binds to Pgp protein in cell membranes inhibiting its transport function. The inhibition of the Pgp transport function has been shown to increase the accumulation of rhodamine-123 and standard cytostatic- doxorubicin in LOVO/DX cells. Our results prove that celastrol exhibits significant chemopreventive and chemosensitizing activities on drug resistant colon cancer cells. Celastrol appears to be a good candidate f...Continue Reading

References

Jan 4, 1989·Journal of the National Cancer Institute·C K Luk, I F Tannock
May 1, 1993·British Journal of Cancer·R KramerI C Summerhayes
Apr 1, 1996·The Journal of Experimental Medicine·M A GoodellR C Mulligan
Jul 1, 1997·Leukemia·J Pétriz, J García-López
Dec 16, 1997·Proceedings of the National Academy of Sciences of the United States of America·E B MechetnerI B Roninson
Aug 16, 2001·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·James C. CusackAlbert S. Baldwin
Aug 22, 2001·Progress in Neuro-psychopharmacology & Biological Psychiatry·A C AllisonC Vigo
Mar 21, 2002·Nature Reviews. Cancer·Michael M GottesmanSusan E Bates
May 27, 2003·Cytometry. Part a : the Journal of the International Society for Analytical Cytology·Suk W ParkEugene Mechetner
Nov 25, 2003·Gut·C G DietrichR P J Oude Elferink
Sep 1, 2004·Biochemical and Biophysical Research Communications·Guillaume F PinnaChristian D Muller
Jan 11, 2005·The Journal of Pathology·D B Longley, P G Johnston
Apr 2, 2005·Nature Reviews. Cancer·Chikashi Nakanishi, Masakazu Toi
Apr 29, 2006·Human Cell·Naotsugu HaraguchiMasaki Mori
Jun 27, 2006·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Tetsuhiro ChibaHideki Taniguchi
Aug 15, 2006·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Naoko YoshidaJunichi Kawakami
Dec 13, 2006·Methods in Enzymology·K K Lin, Margaret A Goodell
Jul 31, 2007·Molecular and Cellular Biochemistry·Matthias ChristgenUlrich Lehmann
Oct 6, 2007·Cancer Biomarkers : Section a of Disease Markers·Toru Kondo
Mar 13, 2008·Gut·L Ricci-VitianiR De Maria
Sep 12, 2008·Nature Reviews. Cancer·Jane E Visvader, Geoffrey J Lindeman
Oct 11, 2008·Cell Death and Differentiation·G KroemerUNKNOWN Nomenclature Committee on Cell Death 2009
Nov 26, 2009·Molecular Cancer Research : MCR·Ming ChenSeth J Orlow
Feb 4, 2010·International Journal of Molecular Medicine·Andrew DavenportQ Ping Dou
May 7, 2010·Blood Cells, Molecules & Diseases·Roberta RiccioniUgo Testa
Mar 10, 2011·Nature Medicine·Hans Clevers
Mar 16, 2011·The Journal of Biological Chemistry·Shivaprasad H VenkateshaKamal D Moudgil
Apr 7, 2011·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Haibo MouNong Xu
Jun 28, 2011·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Zi LiuGuang-Biao Zhou
Feb 4, 2012·The Lancet Oncology·Louis VermeulenJan Paul Medema
Oct 20, 2012·Cytometry. Part a : the Journal of the International Society for Analytical Cytology·Albert D DonnenbergVera S Donnenberg
Feb 2, 2013·Clinical and Translational Medicine·Lissa Nurrul Abdullah, Edward Kai-Hua Chow

❮ Previous
Next ❯

Citations

Feb 23, 2019·International Journal of Immunopathology and Pharmacology·Xuefu LiShuzhen Lv
May 2, 2019·Therapeutic Advances in Medical Oncology·Shuren WangNingzhi Xu
Jun 3, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Janusz PiasnyTomasz Gębarowski
Dec 2, 2020·Materials Science & Engineering. C, Materials for Biological Applications·Mona A AbdelmoneemAhmed O Elzoghby
Apr 4, 2021·International Journal of Molecular Sciences·Rita Martín-RamírezJulio Ávila

❮ Previous
Next ❯

Methods Mentioned

BETA
flow cytometry
Fluorescence
pharmacotherapy
FCS

Software Mentioned

GraphPad Prism
GraphPad
FCS express

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

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.