Abstract
We have previously described the synthesis of a cytotoxic polymeric conjugate of spermine (Poly-SPM) which is able to inhibit the transport of polyamines (spermine, spermidine, and putrescine) into normal and malignant cells. Recent studies examining the toxicity of Poly-SPM in parental and multidrug resistant (MDR) cancer cells have revealed a cross-resistance in the MDR variant Dx5 to the toxic effects of the conjugate in the MDR-positive cells. There were also differences in spermine and putrescine uptake rates between parental and MDR-positive with the MDR-positive cells having a lower Vmax and a higher Km. The ability of this Poly-SPM to reverse MDR was examined in MDR variants (Dx5 cells) of the human sarcoma cell line MES-SA. The cells express high levels of the mdr1 gene product, P-glycoprotein, and are 25-to 60-fold resistant to doxorubicin (DOX), etoposide (VP-16), vinblastine (VBL), and taxol (TAX). Cytotoxicity was measured by the MTT [3-(4,5-dimethyldiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. Poly-SPM (50 microM) lowered the drug concentration IC50 values in the Dx5 cells by 37-fold with VBL, 42-fold with DOX, 29-fold with VP-16, and 25-fold with TAX when compared to the control IC50 values without Poly-SP...Continue Reading
Citations
Jun 27, 2000·Journal of Cellular Physiology·E WangK W Dunn
Aug 11, 1998·Biochemical Pharmacology·S M AzizP A Crooks
Sep 14, 2000·Biomaterials·M TijerinaJ Kopecek
Jun 25, 1998·Journal of Pharmaceutical and Biomedical Analysis·S M AzizP A Crooks
Mar 25, 2004·Breast Cancer Research and Treatment·Baoqing GuoAmadeo M Parissenti
May 30, 2012·Cancer Cell International·Johan KjellströmJohan Wennerberg
Feb 8, 2016·Breast Cancer Research : BCR·Marsela BraunsteinMelanie Spears
Sep 21, 2007·Cancer Treatment Reviews·Britta StordalRoss Davey
Oct 6, 2005·Cancer Cell International·Cheol-Hee Choi
Jan 17, 2015·Cancer Letters·Ching-Ting HuangWen-Fang Cheng
Oct 13, 2011·Journal of Experimental & Clinical Cancer Research : CR·Kuniyasu Soda
Jan 26, 2013·PloS One·Martin P BarrKenneth J O'Byrne
May 3, 2008·Seminars in Oncology·A Jo Chien, Mark M Moasser
Dec 17, 2008·Toxicology·Po-Ni HsiaoWei-Zen Sun
Jan 16, 2008·Cancer Letters·Yaohua Wang, Edgar A Arriaga
Feb 7, 2006·Cancer Letters·Yuko UenoYuji Murata
Sep 11, 1999·Thyroid : Official Journal of the American Thyroid Association·M YatinK B Ain
Dec 21, 2006·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Toshiaki SaekiTakashi Tsuruo
Apr 15, 1997·Cancer·X WuM R Spitz
Sep 15, 2020·Drug Development and Industrial Pharmacy·Zhongjuan WangZhongkun Li
Oct 26, 1999·European Journal of Haematology·J M NørgaardP Hokland
Jan 24, 2018·Bioscience Reports·Huan-Huan ShaJi-Feng Feng
Nov 11, 2005·Journal of Medicinal Chemistry·Brittany LeeR Luise Krauth-Siegel
Jan 5, 2001·Cancer Treatment Reviews·J BartE G de Vries