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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

The Curcumin Analog CH-5 Exerts Anticancer Effects in Human Osteosarcoma Cells via Modulation of Transcription Factors p53/Sp1

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Lima, Felipe Teixeira [1] ; Seba, Viviane [1] ; Silva, Gabriel [1] ; Torrezan, Guilherme Silva [2] ; Polaquini, Carlos Roberto [2] ; Pinhanelli, Vitor Caressato [1] ; Baek, Seung J. [3, 4] ; Fachin, Ana Lucia [5, 1] ; Regasini, Luis Octavio [2] ; Marins, Mozart [5, 1]
Total Authors: 10
[1] Univ Ribeirao Preto, Biotechnol Unit, Av Costabile Romano 2201, BR-14096900 Ribeirao Preto, SP - Brazil
[2] Sao Paulo State Univ UNESP, Inst Biosci Human & Exact Sci, Dept Chem & Environm Sci, Lab Green & Med Chem, BR-15054000 Sao Jose Do Rio Preto, SP - Brazil
[3] Seoul Natl Univ, Coll Vet Med, Lab Signal Transduct, Seoul 08826 - South Korea
[4] Seoul Natl Univ, Res Inst Vet Sci, Seoul 08826 - South Korea
[5] Univ Ribeirao Preto, Med Sch, Av Costabile Romano 2201, BR-14096900 Ribeirao Preto, SP - Brazil
Total Affiliations: 5
Document type: Journal article
Web of Science Citations: 1

Curcumin is a potential anticancer drug with poor bioavailability, which limits its clinical use as a therapeutic agent. The aim of this study was a preliminary evaluation of the curcumin analogue CH-5 as a cytotoxic agent in human osteosarcoma cell lines U2OS, MG-63, and Saos-2. CH-5 inhibited cell viability at lower concentrations than curcumin, leading to the induction of apoptosis. The cellular levels of the transcription factors p53 and Sp1 affect the expression of cellular pathways that lead to apoptosis. CH-5 increased p53 protein levels in U2OS cells and reduced Sp1 levels, with a consequent effect on the expression of their target genes DNA methyltransferase 1 (DNMT1) and growth arrest and DNA damage-inducible 45 alpha gene (Gadd45a). CH-5 repressed DNMT1 and increased Gadd45a mRNA expression, which was dependent on p53, as this effect was only observed in the colorectal cancer cell line HCT116 with active p53, but not in the isogenic p53-deficient HCT116 cells. CH-5 also reduced the protein levels of DNMT1, which led to the upregulation of Gadd45a. These results suggest that CH-5 has potentially higher anticancer activity than curcumin, which is associated with the expression of apoptosis-associated genes regulated by the transcription factors Sp1 and p53. Future work on CH-5 will define the therapeutic potential of this compound in vivo. (AU)

FAPESP's process: 14/15307-7 - Molecular analysis of the response of human and canine tumor strain lines to the flavonoid trans-chalcone
Grantee:Mozart de Azevedo Marins
Support type: Regular Research Grants
FAPESP's process: 14/18330-0 - Synthesis and biological evaluation of curcumin-cinnamaldehyde hybrids as bacterial cell division inhibitors
Grantee:Luis Octávio Regasini
Support type: Regular Research Grants
FAPESP's process: 17/03237-2 - Bioscreening of polyphenols with anticancer activity and investigation of the molecular mechanisms involving the p53 transcription factor
Grantee:Mozart de Azevedo Marins
Support type: Regular Research Grants