Molecular analysis of the response of human and canine tumor strain lines to the flavonoid trans-chalcone

• Grant number: 14/15307-7
• Support Opportunities: Regular Research Grants
• Start date: February 01, 2015
• End date: March 31, 2017
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Mozart de Azevedo Marins
• Grantee: Mozart de Azevedo Marins
• Host Institution: Universidade de Ribeirão Preto (UNAERP). Campus Ribeirão Preto. Ribeirão Preto , SP, Brazil
• Associated researchers: Ana Lucia Fachin Saltoratto ; Houtan Noushmehr

Abstract

Flavonoids are polyphenolic compounds of plant origin that are present in abundance in fruits, vegetables, teas and medicinal herbs. The different molecules in this class of compounds are explored for the development of chemotherapeutic agents with new targets or to sensitization of tumor cells to lower doses of conventional chemotherapeutic agents. Experiments conducted by our research group in strains of human and canine tumor cells demonstrated that the trans-chalcone, an open chain flavonoid, inhibits the gene expression of the enzyme topoisomerase IIa and induces apoptosis, both targets of antitumor drugs. Using "western blot" experiments with the human osteosarcoma cell line U2OS we found that these effects probably occur by increasing the stability of the transcript factor p53 and inhibiting the transcription factor Sp1. These transcription factors interact at promoter regions throughout the genome and define the induction or repression of genes involved in various cellular processes, including apoptosis. In this project, the overall goal is to identify the set of genes modulated by the activity of trans-chalcone over the human osteosarcoma U2OS and canine histiocytic sarcoma DH82 cell lines. This analysis should help identify the mechanisms involved in the citotoxicity of trans-chalcone and identification of genes which may serve as targets for the development of antitumor drugs for the treatment of canine and human cancer. (AU)

Scientific publications

(8)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

SEBA, VIVIANE; SILVA, GABRIEL; DOS SANTOS, MARIANA BASTOS; BAEK, SEUNG JOON; FRANCA, SUZELEI DE CASTRO; FACHIN, ANA LUCIA; REGASINI, LUIS OCTAVIO; MARINS, MOZART. Chalcone Derivatives 4 `-Amino-1-Naphthyl-Chalcone (D14) and 4 `-Amino-4-Methyl-1-Naphthyl-Chalcone (D15) Suppress Migration and Invasion of Osteosarcoma Cells Mediated by p53 Regulating EMT-Related Genes. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 19, n. 9, SEP 2018. (17/03237-2, 14/15307-7)

LIMA, FELIPE TEIXEIRA; SEBA, VIVIANE; SILVA, GABRIEL; TORREZAN, GUILHERME SILVA; POLAQUINI, CARLOS ROBERTO; PINHANELLI, VITOR CARESSATO; BAEK, SEUNG J.; FACHIN, ANA LUCIA; REGASINI, LUIS OCTAVIO; MARINS, MOZART. The Curcumin Analog CH-5 Exerts Anticancer Effects in Human Osteosarcoma Cells via Modulation of Transcription Factors p53/Sp1. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 19, n. 7, JUL 2018. (17/03237-2, 14/15307-7, 14/18330-0)

SEBA, VIVIANE; SILVA, GABRIEL; DOS SANTOS, MARIANA BASTOS; BAEK, SEUNG JOON; FRANCA, SUZELEI DE CASTRO; FACHIN, ANA LUCIA; REGASINI, LUIS OCTAVIO; MARINS, MOZART. Chalcone Derivatives 4 '-Amino-1-Naphthyl-Chalcone (D14) and 4 '-Amino-4-Methyl-1-Naphthyl-Chalcone (D15) Suppress Migration and Invasion of Osteosarcoma Cells Mediated by p53 Regulating EMT-Related Genes. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 19, n. 9, p. 13-pg., 2018-09-01. (14/15307-7, 17/03237-2)

SANTOS, MARIANA B.; PINHANELLI, VITOR C.; GARCIA, MAYARA A. R.; SILVA, GABRIEL; BAEK, SEUNG J.; FRANCA, SUZELEI C.; FACHIN, ANA L.; MARINS, MOZART; REGASINI, LUIS O.. Antiproliferative and pro-apoptotic activities of 2 '- and 4 '-aminochalcones against tumor canine cells. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, v. 138, p. 6-pg., 2017-09-29. (14/15307-7, 14/18330-0)

LIMA, FELIPE TEIXEIRA; SEBA, VIVIANE; SILVA, GABRIEL; TORREZAN, GUILHERME SILVA; POLAQUINI, CARLOS ROBERTO; PINHANELLI, VITOR CARESSATO; BAEK, SEUNG J.; FACHIN, ANA LUCIA; REGASINI, LUIS OCTAVIO; MARINS, MOZART. The Curcumin Analog CH-5 Exerts Anticancer Effects in Human Osteosarcoma Cells via Modulation of Transcription Factors p53/Sp1. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 19, n. 7, p. 14-pg., 2018-07-01. (14/15307-7, 17/03237-2, 14/18330-0)

SILVA, GABRIEL; MARINS, MOZART; CHAICHANASAK, NADDA; YOON, YONGDAE; FACHIN, ANA LUCIA; PINHANELLI, VITOR CARESSATO; REGASINI, LUIS OCTAVIO; DOS SANTOS, MARIANA BASTOS; AYUSSO, GABRIELA MIRANDA; MARQUES, BEATRIZ DE CARVALHO; et al. Trans-chalcone increases p53 activity via DNAJB1/HSP40 induction and CRM1 inhibition. PLoS One, v. 13, n. 8, AUG 17 2018. (14/15307-7)

SANTOS, MARIANA B.; PINHANELLI, VITOR C.; GARCIA, MAYARA A. R.; SILVA, GABRIEL; BAEK, SEUNG J.; FRANCA, SUZELEI C.; FACHIN, ANA L.; MARINS, MOZART; REGASINI, LUIS O.. Antiproliferative and pro-apoptotic activities of 2 `- and 4 `-aminochalcones against tumor canine cells. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, v. 138, p. 884-889, SEP 29 2017. (14/15307-7, 14/18330-0)

SILVA, GABRIEL; LIMA, FELIPE TEIXEIRA; SEBA, VIVIANE; MENDES LOURENCO, ANA LAURA; LUCAS, THAISE GRAMINHA; DE ANDRADE, BIANCA VIEIRA; TORREZAN, GUILHERME SILVA; POLAQUINI, CARLOS ROBERTO; GARCIA, MARCELO ENGRACIA; COUTO, LUCELIO BERNARDES; et al. Curcumin Analog CH-5 Suppresses the Proliferation, Migration, and Invasion of the Human Gastric Cancer Cell Line HGC-27. Molecules, v. 23, n. 2, FEB 2018. (17/03237-2, 14/18330-0, 14/15307-7)