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Cytotoxic and proapototic activity of reveratrol analogues in breast cancer cell lines structure activity relationship (SAR)
Author(s) -
Murias Marek,
Piesik Joanna,
Handler Norbert,
Erker Thomas,
JodynisLiebert Jadwiga
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1141-c
Subject(s) - chemistry , cytotoxicity , antioxidant , polyphenol , stereochemistry , cancer cell , pinoresinol , cyp1b1 , cell culture , cytotoxic t cell , biochemistry , apoptosis , cancer , cancer research , in vitro , lignan , cytochrome p450 , enzyme , biology , medicine , genetics
The polyphenol resveratrol (3,4′,5‐trihydroxy‐stilbene, 3,4′,5‐THS, RES) is anticancer agent. Besides glucuronidation and sulfation, RES is hydroxylated by CYP1B1 to form 3,3′,4′,5‐HS and 3,4,4′,5‐HS a metabolites with higher anticancer and antioxidant properties. It was hypothesized that RES analogues (RA) possessing more then 3 phenolic groups may act stronger against cancer cells than RES. In order to investigate a possible SAR between pro/antioxidant properties and cytotoxicity, the following RA with at least 2 phenolic groups in neighborhood: 3,3′,4′,5‐HS, 3,4,4′,5‐HS, 4,4′,5,5′‐HS, 3,3′,4,5,5′‐HS, 3,3′,4,4′,5,5′‐HS and without such a structure: RES and 3,3′,5,5′‐HS, were synthesized. Previously we have shown that the cytotoxiciy of RA may correlate with the formation of antioxidant‐derived prooxidants when at least 2 hydroxyl groups are present in neighboring positions forming prooxidative semiquinones. Presently we have tested this hypothesis in cell culture using ZR‐75‐1 and MDA‐MB‐231 breast cancer cells. Conclusion semiquinone forming RA act stronger than RES against breast cancer cells mainly via necrotic way, while RES and 3,3′,5,5′‐HS worked as apoptose inducing agents. The high level of expression of sulfotransferases mRNA did not change anticancer potential of RA which form semiquinones, but protected cells against RES and 3,3′,5,5′‐HS. MM thanks EC for M. Curie Reintegration Grant