Role of CYP1A1 in the biological activity of methylated resveratrol analogue, 3,4,5,4′-tetramethoxystilbene (DMU-212) in ovarian cancer A-2780 and non-cancerous HOSE cells

Piotrowska‐Kempisty, Hanna; Klupczyńska, Agnieszka; Trzybulska, Dorota; Kulcenty, Katarzyna; Sulej-Suchomska, Anna Maria; Kucińska, Małgorzata; Mikstacka, Renata; Wierzchowski, Marcin; Murias, Marek; Baer‐Dubowska, Wanda; Kokot, Zenon J.; Jodynis‐Liebert, Jadwiga

doi:10.1016/j.toxlet.2016.12.018

Cited by 26 publications

(21 citation statements)

References 22 publications

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“…It was found that DMU-212 induced AhR activation in HepG2 stably transfected line AZ-AhR [75]. In contrast, another study showed that DMU-214 at a concentration of 0.25 µM might decrease the level of the AhR nuclear fraction and thus, exert the inhibitory effect on CYP1A1 [86].…”

Section: Short Story About Dmu-212-when Synthetic Chemistry Achieved mentioning

confidence: 94%

“…In 2005, McErlane et al suggested that DMU-212 is inactive until it undergoes aromatic hydroxylation (by CYP1A1) and O-demethylation (by CYP1B1) to generate two active metabolites, DMU-214 (referred as a tyrosine kinase inhibitor) and DMU-291 (apoptosis inducer), respectively [85]. Further studies showed that the human cytochrome P450 1A1 (CYP1A1) is mainly involved in the DMU-212 metabolic pathway [75,86]. The dose-dependent induction of CYP1A1 and CYP1A2 mRNAs was noted after treatment of primary human hepatocytes cells with DMU-212 [75].…”

Section: Short Story About Dmu-212-when Synthetic Chemistry Achieved mentioning

confidence: 99%

“…The dose-dependent induction of CYP1A1 and CYP1A2 mRNAs was noted after treatment of primary human hepatocytes cells with DMU-212 [75]. This metabolic activation is probably involved in anticancer activity, while it was found that the lack of the expression of CYP1A1 is associated with lower activity of DMU-212 [86]. The important role in CYP1A1 activation may play the aryl hydrocarbon receptor (AhR).…”

Section: Short Story About Dmu-212-when Synthetic Chemistry Achieved mentioning

confidence: 99%

“…Therefore, the regulation of CYP1B1 expression can act as a therapeutic strategy, especially for cancer treatment. Taking into account the role of CYP1A1 in DMU-212 activation, it is suggested that its metabolite DMU-214 may act as both a CYP1A1 and CYP1B1 inhibitor [86].…”

Section: Short Story About Dmu-212-when Synthetic Chemistry Achieved mentioning

confidence: 99%

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More Than Resveratrol: New Insights into Stilbene-Based Compounds

et al. 2020

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The concept of a scaffold concerns many aspects at different steps on the drug development path. In medicinal chemistry, the choice of relevant “drug-likeness” scaffold is a starting point for the design of the structure dedicated to specific molecular targets. For many years, the chemical uniqueness of the stilbene structure has inspired scientists from different fields such as chemistry, biology, pharmacy, and medicine. In this review, we present the outstanding potential of the stilbene-based derivatives. Naturally occurring stilbenes, together with powerful synthetic chemistry possibilities, may offer an excellent approach for discovering new structures and identifying their therapeutic targets. With the development of scientific tools, sophisticated equipment, and a better understanding of the disease pathogenesis at the molecular level, the stilbene scaffold has moved innovation in science. This paper mainly focuses on the stilbene-based compounds beyond resveratrol, which are particularly attractive due to their biological activity. Given the “fresh outlook” about different stilbene-based compounds starting from stilbenoids with particular regard to isorhapontigenin and methoxy- and hydroxyl- analogues, the update about the combretastatins, and the very often overlooked and underestimated benzanilide analogues, we present a new story about this remarkable structure.

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Section: Short Story About Dmu-212-when Synthetic Chemistry Achieved mentioning

confidence: 94%

Section: Short Story About Dmu-212-when Synthetic Chemistry Achieved mentioning

confidence: 99%

Section: Short Story About Dmu-212-when Synthetic Chemistry Achieved mentioning

confidence: 99%

Section: Short Story About Dmu-212-when Synthetic Chemistry Achieved mentioning

confidence: 99%

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More Than Resveratrol: New Insights into Stilbene-Based Compounds

et al. 2020

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“…Thus, its analogs showing improved pharmacokinetic parameters and enhanced activity are searched. Comparing to resveratrol, its derivatives with ortho -methoxy substituents, such as 3,4,5,4′-tetramethoxy- trans -stilbene (DMU-212), have been found to be more potent anti-carcinogenic agents in some in vitro and in vivo studies [ 3 , 4 ]. Moreover, our earlier data showed that the new synthetic methoxy-stilbenes, 3,4,2′-trimethoxy- trans -stilbene (3MS), 3,4,2′,4′-tetramethoxy- trans -stilbene (4MS), and 3,4,2′,4′,6′-pentamethoxy- trans -stilbene (5MS), modulated the constitutive expression of enzymes and receptors involved in estrogen synthesis and catabolism in breast immortalized epithelial MCF10 cells.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of the effect of the new methoxy-stilbenes on expression of receptors and enzymes involved in estrogen synthesis in cancer breast cells

et al. 2017

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Our previous study showed that the new synthetic methoxy-stilbenes, 3,4,2′-trimethoxy-trans-stilbene (3MS), 3,4,2′,4′-tetramethoxy-trans-stilbene (4MS), and 3,4,2′,4′,6′-pentamethoxy-trans-stilbene (5MS), modulate the constitutive expression of enzymes and receptors involved in estrogen metabolism in breast immortalized epithelial MCF10 cells. In this study, we evaluated the effect of 3MS, 4MS, and 5MS in comparison to resveratrol activity in MCF7 estrogen-dependent and MDA-MB-231 estrogen-independent breast cancer cell lines. 3MS similarly to resveratrol reduced the expression of estrogen receptor α in MCF7 cells. However, in these cells, 5MS reduced the most CYP19, the gene encoding aromatase, at mRNA transcript level. In contrast, in the MDA-MB-231 cells, the most efficient inhibitor of CYP19 expression was 3MS, reducing the level of its protein by ~ 25%. This stilbene also inhibited the aromatase activity in a recombinant protein system with IC50 value ~ 85 µM. Treatment with the methoxy-stilbenes reduced the level of estradiol in culture medium. The most significant reduction was exerted by 3MS. None of the tested stilbenes including resveratrol changed significantly the expression of AhR, although CYP1A1 protein level was slightly reduced in MDA-MB-231 cells, while CYP1B1 expression was increased in these cells as a result of treatment with 3MS, but only at the transcript level. Overall, these results show weak or moderate effect of the new methoxy-stilbenes on the expression of key proteins involved in estrogens metabolism in cancer breast cells. However, the reduced CYP19 expression and activity upon 3MS treatment in metastatic MDA-MB-231 cells require the further studies.

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Synthesis of Hydroxylated Stilbenes in a Batch and Flow Reactor: An Overview

Ljubić,

Šalić,

Škorić

2023

ChemistrySelect

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With the increasing awareness of cardiovascular diseases and cancer prevention, the interest in resveratrol and its derivatives, i. e. hydroxylated stilbene compounds, as great antioxidants is growing day by day. The discovery of several other stilbene applications, especially in the treatment of numerous diseases, has further increased interest. Antidiabetic, anti‐inflammatory, antimicrobial, and anti‐neurodegenerative are just a few of the properties attributed to hydroxylated stilbene compounds. It is therefore not surprising that hydroxylated stilbenes are of great importance and frequently researched nowadays. In parallel, research in the field of flow chemistry has been increasing rapidly for years, as it offers many advantages in many different fields, including the synthesis of hydroxylated stilbenes. In this review article, a concise overview of stilbene compounds is given, as well as their properties and biological activity depending on the structure. In addition, various and common synthesis and production methods are described, with emphasis on application of flow chemistry in these processes.

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Role of CYP1A1 in the biological activity of methylated resveratrol analogue, 3,4,5,4′-tetramethoxystilbene (DMU-212) in ovarian cancer A-2780 and non-cancerous HOSE cells

Cited by 26 publications

References 22 publications

More Than Resveratrol: New Insights into Stilbene-Based Compounds

More Than Resveratrol: New Insights into Stilbene-Based Compounds

Evaluation of the effect of the new methoxy-stilbenes on expression of receptors and enzymes involved in estrogen synthesis in cancer breast cells

Synthesis of Hydroxylated Stilbenes in a Batch and Flow Reactor: An Overview

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