The Combined Use of Phenothiazines and Statins Strongly Affects Doxorubicin-Resistance, Apoptosis, and Cox-2 Activity in Colon Cancer Cells

International Journal of Molecular Sciences
Kamila Środa-PomianekOlga Wesołowska

Abstract

Since none of the multidrug resistance (MDR) modulators tested so far found their way into clinic, a novel approach to overcome the MDR of cancer cells has been proposed. The combined use of two MDR modulators of dissimilar mechanisms of action was suggested to benefit from the synergy between them. The effect of three phenothiazine derivatives that were used as single agents and in combination with simvastatin on cell growth, apoptosis induction, activity, and expression of cyclooxygenase-2 (COX-2) in doxorubicin-resistant colon cancer cells (LoVo/Dx) was investigated. Treatment of LoVo/Dx cells by phenothiazine derivatives combined with simvastatin resulted in an increase of doxorubicin cytotoxicity and its intracellular accumulation as compared to the treatment with phenothiazine derivatives that were used as single agents. Similarly, LoVo/Dx cells treated with two-component mixture of modulators showed the reduced expression of ABCB1 (P-glycoprotein) transporter and COX-2 enzyme, both on mRNA and protein level. Reduced expression of anti-apoptotic Bcl-2 protein and increased expression of pro-apoptotic Bax were also detected. Additionally, COX-2 activity was diminished, and caspase-3 activity was increased to a higher exten...Continue Reading

References

Jul 4, 1990·Journal of the National Cancer Institute·P SkehanM R Boyd
May 1, 1988·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·R L MillerR Ganapathi
Jan 1, 1999·Bioorganic & Medicinal Chemistry Letters·K D StewartK I Hulkower
Jun 6, 2006·Biochemical and Biophysical Research Communications·Attila KónyaIstván Kurucz
Feb 24, 2007·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Aïda HabibKamal F Badr
Jan 4, 2008·International Journal of Cancer. Journal International Du Cancer·Hang XiaoChung S Yang
Jan 18, 2008·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Ashraful HoqueXiao-Chun Xu
Feb 6, 2008·Expert Opinion on Drug Metabolism & Toxicology·Suneet ShuklaSuresh V Ambudkar
Jun 4, 2008·International Journal of Cancer. Journal International Du Cancer·Soo-Jeong ChoIn Sung Song
Jun 27, 2008·Cellular and Molecular Life Sciences : CMLS·H Lage
Jun 16, 2009·Medicinal Research Reviews·Marek Jakobisiak, Jakub Golab
Sep 10, 2009·International Journal of Cancer. Journal International Du Cancer·Evelyn SieczkowskiMartin Hohenegger
Jul 17, 2010·European Journal of Pharmacology·Olga WesołowskaKrystyna Michalak
Feb 26, 2011·International Journal of Cancer. Journal International Du Cancer·Carolyn A GoardLinda Z Penn
Nov 23, 2011·Pharmacological Reviews·Patrizia GazzerroMaurizio Bifulco
Mar 7, 2012·Antimicrobial Agents and Chemotherapy·Jérôme DormoiBruno Pradines
Apr 30, 2015·Asian Pacific Journal of Cancer Prevention : APJCP·Zhen-Qin Qiu, Zhen-Rong Qiu
Aug 31, 2016·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Alice C RodriguesAi-Ming Yu
Oct 30, 2016·Anticancer Research·Gabriella SpenglerLeonard Amaral
Jan 23, 2017·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Anna Palko-LabuzKrystyna Michalak
Oct 25, 2017·Anticancer Research·Borisz VargaGabriella Spengler
Jul 1, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Mahendra SeerviT R Santhosh Kumar
Dec 16, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Anna Palko-ŁabuzKrystyna Michalak

❮ Previous
Next ❯

Citations

Aug 28, 2020·Journal of Applied Toxicology : JAT·Michał Otręba, Leon Kośmider
Aug 20, 2020·Seminars in Cancer Biology·Amir R AfshariAmirhossein Sahebkar
Oct 1, 2021·Drug Discovery Today·Diana Duarte, Nuno Vale

❮ Previous
Next ❯

Methods Mentioned

BETA
Assay

Software Mentioned

CompuSyn
Gel Documented System KODAK MI
Image J

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.