In Vitro Anticancer Activity and Mechanism of Action of an Aziridinyl Galactopyranoside

Burgos-Moron, EstefaniaUniv Seville, Fac Pharm, Dept Pharmacol, Seville 41012, Spain. (author)

We recently screened a series of new aziridines beta-D-galactopyranoside derivatives for selective anticancer activity and identified 2-methyl-2,3-[N-(4-methylbenzenesulfonyl)imino]propyl 2,3-di-O-benzyl-4,6-O-(S)-benzylidene-beta-D-galactopyranoside (AzGalp) as the most promising compound. In this article, we explore the possible mechanisms involved in the cytotoxicity of this aziridine and evaluate its selective anticancer activity using cancer cells and normal cells from a variety of tissues. Our data show that AzGalp induces DNA damage (comet assay). Cells deficient in the nucleotide excision repair (NER) pathway were hypersensitive to the cytotoxicity of this compound. These results suggest that AzGalp induces bulky DNA adducts, and that cancer cells lacking a functional NER pathway may be particularly vulnerable to the anticancer effects of this aziridine. Several experiments revealed that neither the generation of oxidative stress nor the inhibition of glycolysis played a significant role in the cytotoxicity of AzGalp. Combinations of AzGalp with oxaliplatin or 5-fluorouracil slightly improved the ability of both anticancer drugs to selectively kill cancer cells. AzGalp also showed selective cytotoxicity against a panel of malignant cells versus normal cells; the highest selectivity was observed for two acute promyelocytic leukemia cell lines. Additional preclinical studies are necessary to evaluate the anticancer potential of AzGalp.

MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Cancer och onkologi hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Cancer and Oncology hsv//eng
TEKNIK OCH TEKNOLOGIER Nanoteknik hsv//swe
ENGINEERING AND TECHNOLOGY Nano-technology hsv//eng
aziridine
cancer
cytotoxic
cytotoxicity
selectivity
nucleotide excision repair
Engineering Science with specialization in Nanotechnology and Functional Materials
Teknisk fysik med inriktning mot nanoteknologi och funktionella material

Pastor, NuriaUniv Seville, Fac Biol, Dept Cell Biol, Seville 41012, Spain. (author)
Orta, Manuel LuisUniv Seville, Fac Biol, Dept Cell Biol, Seville 41012, Spain. (author)
Jimenez-Alonso, Julio JoseUniv Seville, Fac Pharm, Dept Pharmacol, Seville 41012, Spain. (author)
Palo-Nieto, CarlosUppsala universitet,Nanoteknologi och funktionella material,Institutionen för läkemedelskemi,Univ Seville, Fac Pharm, Dept Organ & Med Chem, Seville 41012, Spain.(Swepub:uu)carpa373 (author)
Vega-Holm, MargaritaUniv Seville, Fac Pharm, Dept Organ & Med Chem, Seville 41012, Spain. (author)
Vega-Perez, Jose ManuelUniv Seville, Fac Pharm, Dept Organ & Med Chem, Seville 41012, Spain. (author)
Iglesias-Guerra, FernandoUniv Seville, Fac Pharm, Dept Organ & Med Chem, Seville 41012, Spain. (author)
Mateos, SantiagoUniv Seville, Fac Biol, Dept Cell Biol, Seville 41012, Spain. (author)
Lopez-Lazaro, MiguelUniv Seville, Fac Pharm, Dept Pharmacol, Seville 41012, Spain. (author)
Calderon-Montano, Jose ManuelUniv Seville, Fac Pharm, Dept Pharmacol, Seville 41012, Spain. (author)
Univ Seville, Fac Pharm, Dept Pharmacol, Seville 41012, Spain.Univ Seville, Fac Biol, Dept Cell Biol, Seville 41012, Spain. (creator_code:org_t)

By the author/editor: Burgos-Moron, Es ...; Pastor, Nuria; Orta, Manuel Lui ...; Jimenez-Alonso, ...; Palo-Nieto, Carl ...; Vega-Holm, Marga ...; show more...; Vega-Perez, Jose ...; Iglesias-Guerra, ...; Mateos, Santiago; Lopez-Lazaro, Mi ...; Calderon-Montano ...; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Cancer and Oncol ...

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