Design, Synthesis, and Biological Activity of a Family of Novel Ceramide Analogues in Chemoresistant Breast Cancer Cells

被引：36

作者：

Antoon, James W. ^{[2
,3
]}

Liu, Jiawang ^{[1
]}

Gestaut, Matthew M. ^{[2
,3
]}

Burow, Matthew E. ^{[2
,3
]}

Beckman, Barbara S. ^{[2
,3
]}

Foroozesh, Maryam ^{[1
]}

机构：

[1] Xavier Univ, Dept Chem, New Orleans, LA 70125 USA

[2] Tulane Univ, Sch Med, Dept Pharmacol, New Orleans, LA 70112 USA

[3] Tulane Univ, Sch Med, Dept Med, New Orleans, LA 70112 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2009年 / 52卷 / 18期

关键词：

CARCINOMA CELLS; RESISTANCE; DEATH; GLUCOSYLCERAMIDE; ACTIVATION; EXPRESSION; PATHWAY;

D O I：

10.1021/jm9009668

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Resistance to chemotherapy and endocrine therapy is a major cause of breast cancer treatment failure. We have synthesized six novel analogues using C8-ceramide as the lead analogue and studied their effect on hormone therapy resistant (MDA-MB-231) and chemoresistant (MCF-7TN-R) breast cancer cells. Pharmacologic intervention using these ceramide analogues inhibited clonogenic survival and induced apoptosis, with one analogue being more effective than C8-ceramide. Our results show ceramide-based therapy has therapeutic potential in treating drug resistant breast cancer.

引用

页码：5748 / 5752

页数：5

共 13 条

[1] Analysis of human breast adenocarcinoma MCF7 resistance to tumor necrosis factor-induced cell death -: Lack of correlation between JNK activation and ceramide pathway [J].

Ameyar, M ;

Atfi, A ;

Cai, ZZ ;

Stancou, R ;

Shatrov, V ;

Bettaïeb, A ;

Chouaïb, S .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (44) :29002-29008

[2] Ceramide and glucosylceramide upregulate expression of the multidrug resistance gene MDR1 in cancer cells [J].

Gouaze-Andersson, Valerie ;

Yu, Jing Y. ;

Kreitenberg, Adam J. ;

Bielawska, Alicja ;

Giuliano, Armando E. ;

Cabot, Myles C. .

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS, 2007, 1771 (12) :1407-1417

[3] A role for ceramide in driving cancer cell resistance to doxorubicin [J].

Liu, Yong-Yu ;

Yu, Jing Yuan ;

Yin, Dongmei ;

Patwardhan, Gauri Anand ;

Gupta, Vineet ;

Hirabayashi, Yoshio ;

Holleran, Walter M. ;

Giuliano, Armando E. ;

Jazwinski, S. Michal ;

Gouaze-Andersson, Valerie ;

Consoli, David P. ;

Cabot, Myles C. .

FASEB JOURNAL, 2008, 22 (07) :2541-2551

[4] Expression of glucosylceramide synthase, converting ceramide to glucosylceramide, confers adriamycin resistance in human breast cancer cells [J].

Liu, YY ;

Han, TY ;

Giuliano, AE ;

Cabot, MC .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (02) :1140-1146

[5]

Lucci A, 1999, INT J ONCOL, V15, P535

[6] RETRACTED: Interleukin-12 deficiency is permissive for angiogenesis in UV radiation-induced skin tumors (Retracted article. See vol. 78, pg. 6708, 2018) [J].

Meeran, Syed M. ;

Katiyar, Suchitra ;

Elmets, Craig A. ;

Katiyar, Santosh K. .

CANCER RESEARCH, 2007, 67 (08) :3785-3793

[7]

Qiu LH, 2006, ONCOL REP, V16, P907

[8] Ceramide synthases and ceramide levels are increased in breast cancer tissue [J].

Schiffmann, Susanne ;

Sandner, Jessica ;

Birod, Kerstin ;

Wobst, Ivonne ;

Angioni, Carlo ;

Ruckhaeberle, Eugen ;

Kaufmann, Manfred ;

Ackermann, Hanns ;

Loetsch, Joern ;

Schmidt, Helmut ;

Geisslinger, Gerd ;

Groesch, Sabine .

CARCINOGENESIS, 2009, 30 (05) :745-752

[9]

Shabbits JA, 2002, MOL CANCER THER, V1, P205

[10] Apoptosis, chemoresistance, and breast cancer: Insights from the MCF-7 cell model system [J].

Simstein, R ;

Burow, M ;

Parker, A ;

Weldon, C ;

Beckman, B .

EXPERIMENTAL BIOLOGY AND MEDICINE, 2003, 228 (09) :995-1003

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