Anti-proliferative effects of novel glyco-lipid-arsenicals (III) on MCF-7 human breast cancer cells.
Arsenic trioxide appears to be effective in the treatment of pro-myelocytic leukaemia. The substituted phenylarsen(III)oxides are highly polar, they have a high tendency to undergo oxidation to As (V) and to form oligomers, to prevent this we protected the As-(OH)(2) group as cyclic dithiaarsanes. To increase the compound's biological stability and passive diffusion we conjugated the compound of interest with lipoamino acids (Laas). Alternatively, we further conjugated the dithiaarsane derivative with a carbohydrate to utilize active transport systems and to target compound. We investigated two novel glyco-lipid arsenicals (III) (compounds 9 and 11) for their ability to initiate MCF-7 breast cancer cell death and characterized the mechanism by which death was initiated. A significant decrease in MCF-7 cell proliferation was observed using 1 microM and 10 microM compound (11) and 10 microM of compound (9). Treatment with compound (11) triggered apoptosis of MFC-7 cells while compound (9) induced inhibition of cellular proliferation was not via rapid induction of apoptosis and more likely reflected necrosis and/or alterations in the cell cycle. Differences in the anti-proliferative potency of the two compounds indicate that structural modifications influence effectiveness.
Wimmer
Norbert
N
School of Molecular and Microbial Sciences, School of Pharmacy, The University of Queensland, Brisbane, Qld 4072, Australia.
Robinson
Jodie A
JA
Gopisetty-Venkata
Nagaraj
N
Roberts-Thomson
Sarah J
SJ
Monteith
Gregory R
GR
Toth
Istvan
I
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001152:Arsenicals / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000473:pathology; D002412:Cations; D016923:Cell Death / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D006017:Glycolipids / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D001152:Arsenicals; D002412:Cations; D006017:Glycolipids