Effects of a combretastatin A4 analogous chalcone and its Pt-complex on cancer cells: A comparative study of uptake, cell cycle and damage to cellular compartments

Abstract

Effects of a combretastatin A4 analogous chalcone and its Pt-complex on cancer cells: a comparative study of uptake, cell cycle and damage to cellular compartments. Biochemical Pharmacology, Elsevier, 2010, 80 (10) Please cite this article as: Zoldakova M, Kornyei Z, Brown A, Biersack B, Madarász E, Schobert R, Effects of a combretastatin A4 analogous chalcone and its Pt-complex on cancer cells: a comparative study of uptake, cell cycle and damage to cellular compartments, Biochemical Pharmacology (2008Pharmacology ( ), doi:10.1016Pharmacology ( /j.bcp.2010 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Page 1 of 48A c c e p t e d M a n u s c r i p t 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 Effects of a combretastatin A4 analogous chalcone and its Pt ((classification: antibiotics and chemotherapeutics))Page 2 of 48 A c c e p t e d M a n u s c r i p t 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 2 ((Abstract))The combretastatin A4 analogous chalcone (2E)-3-(3-hydroxy-4-methoxyphenyl)-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one 1 and its dichloridoplatinum(II) (6-aminomethylnicotinate) complex 2 were previously found to be highly active against a variety of cancer cell lines while differing in their apoptosis induction and long-term regrowth retardation (Schobert R et al. J Med Chem 2009;52:241-6) [1]. Further differences were identified now.The cellular uptake of complex 2, like that of oxaliplatin, occurred mainly via organic cation transporters (OCT-1/2; ~32%) and copper transporter related proteins (Ctr1; ~24%), whereas that of chalcone 1 was dependent on endocytosis (~80%). Complex 2 was more tumourspecific than 1 concerning neural cells. This was apparent from the ratios of IC 50 (48 h) values against primary astrocytes versus human astroglioma cells U87 ( > 7000 for complex 2; 55 for compound 1). In tubulin-rich neurons and 518A2 melanoma cells complex 2 disrupted microtubules and actin filaments. Cancer cells treated with 2 could repair the cytoskeletal damage but ceased to proliferate and perished. Complex 2 was particularly cytotoxic against P-gp-rich cells. It acted as a substrate for ABC-transporters of types BCRP, MRP3, and MRP1 and so was less active against the corresponding can...

Novel synthetic chalcones induces apoptosis in human glioblastoma cells

“…Also, several studies revealed that some chalcones and flavonoids can trigger apoptosis by modulating signaling pathways such as phosphatidylinositol-3-kinase/Akt and MAPK (mitogen-activated protein kinase), affecting many cellular functions such as gene regulation (Zoldakova et al 2010). Other studies report that chalcones actively interfere in ROS levels in T98G and U87MG glioma cell lines, causing changes in mitochondrial potential and MAPKs phosphorylation (Wiseman & Halliwell 1996).…”

(Carboxydiamine)Pt(ii) complexes of a combretastatin A-4 analogous chalcone: the influence of the diamine ligand on DNA binding and anticancer effects

“…10,11 Now we could show them by light microscopy to also cause inter-nucleosomal DNA cleavage in 518A2 melanoma cells (Fig. 10,11 Now we could show them by light microscopy to also cause inter-nucleosomal DNA cleavage in 518A2 melanoma cells (Fig.…”

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Molecular Targeted Approaches to Cancer Therapy and Prevention Using Chalcones

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