Stilbenes as multidrug resistance modulators and apoptosis inducers in human adenocarcinoma cells.
BACKGROUND
The search for promising modulators of cancer multidrug resistance (MDR) that are able to reduce the activity of P-glycoprotein, thus restoring the cytotoxicity of anticancer drugs, is ongoing. The identification of compounds that overcome the apoptosis deficiency that frequently accompanies MDR is also of great therapeutic importance.


METHODS
Four stilbenes, resveratrol, piceatannol and its two derivatives, were tested for their MDR-modulating and apoptosis-inducing activity in drug-sensitive (LoVo) and doxorubicin-resistant human adenocarcinoma cell line (LoVo/Dx) by means of flow cytometry and fluorescence microscopy.


RESULTS
Trans-3,5,3',4'-tetramethoxystilbene (PicMet) was identified as a promising modulator that efficiently increased accumulation of both rhodamine 123 and doxorubicin inside resistant cells. It also increased sensitivity of LoVo/Dx cells to doxorubicin. Resveratrol and trans-3,5,3',4'-tetracetoxystilbene (PicAcet) were identified as apoptosis inducers in LoVo/Dx cells.


CONCLUSIONS
The stilbene structure may constitute a promising chemical scaffold for the synthesis of potential MDR modulators.
Department of Biophysics, Wrocław Medical University, 50-368 Wrocław, Poland. olawes@biofiz.am.wroc.pl
Olga
O
Wesolowska
Jerzy
J
Wisniewski
Aleksandra
A
Bielawska-Pohl
Maria
M
Paprocka
Noelia
N
Duarte
Maria-José U
MJ
Ferreira
Danuta
D
Dus
Krystyna
K
Michalak
D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005434:Flow Cytometry; D006801:Humans; D013267:Stilbenes / Q000494:pharmacology*
D013267:Stilbenes