3-Heptylidene-4,6-Dimethoxy-3<i>H</i>-Isobenzofuran-1-One Is Genotoxic, Increases the Frequency of Cell Death, and Potentiates the Effects of Cyclophosphamide and Cisplatin
Silvia Cordeiro das Neves,
Flavio Henrique de Araújo,
Willian Ayala Correa,
Allana Cristina Faustino Martins,
Henrique Rodrigues Scherer Coelho,
Marcelo Luiz Brandão Vilela,
Valter Aragão do Nascimento,
Candida Aparecida Leite Kassuya,
Dênis Pires de Lima,
Adilson Beatriz,
Rodrigo Juliano Oliveira,
Roberto da Silva Gomes
Affiliations
Silvia Cordeiro das Neves
Stem Cell, Cell Therapy and Toxicological Genetics Research Centre (CeTroGen), Medical School, Federal University of Mato Grosso do Sul, Campo Grande 79080-190, MS, Brazil
Flavio Henrique de Araújo
Stem Cell, Cell Therapy and Toxicological Genetics Research Centre (CeTroGen), Medical School, Federal University of Mato Grosso do Sul, Campo Grande 79080-190, MS, Brazil
Willian Ayala Correa
Institute of Chemistry, Federal University of Mato Grosso do Sul, Campo Grande 79070-900, MS, Brazil
Allana Cristina Faustino Martins
Department of Pharmaceutical Sciences, North Dakota State University, Fargo, ND 58102, USA
Henrique Rodrigues Scherer Coelho
Stem Cell, Cell Therapy and Toxicological Genetics Research Centre (CeTroGen), Medical School, Federal University of Mato Grosso do Sul, Campo Grande 79080-190, MS, Brazil
Marcelo Luiz Brandão Vilela
Medical School, Federal University of Mato Grosso do Sul, Campo Grande 79070-900, MS, Brazil
Valter Aragão do Nascimento
Graduate Programme in Health and Development in the Midwest Region, Medical School, Federal University of Mato Grosso do Sul, Campo Grande 79070-900, MS, Brazil
Candida Aparecida Leite Kassuya
School of Health Sciences, Federal University of Grande Dourados, Dourados 79070-900, MS, Brazil
Dênis Pires de Lima
Institute of Chemistry, Federal University of Mato Grosso do Sul, Campo Grande 79070-900, MS, Brazil
Adilson Beatriz
Institute of Chemistry, Federal University of Mato Grosso do Sul, Campo Grande 79070-900, MS, Brazil
Rodrigo Juliano Oliveira
Stem Cell, Cell Therapy and Toxicological Genetics Research Centre (CeTroGen), Medical School, Federal University of Mato Grosso do Sul, Campo Grande 79080-190, MS, Brazil
Roberto da Silva Gomes
Department of Pharmaceutical Sciences, North Dakota State University, Fargo, ND 58102, USA
3-heptylidene-4,6-dimethoxy-3H-isobenzofuran-1-one (Phthalide 1) is the precursor of three resorcinol lipids that have been described as potential chemotherapeutic agents and capable of potentiating the effects of cyclophosphamide. In this study, we evaluated the genotoxic potential, cell-killing potential, and interactions with cyclophosphamide and cisplatin of phthalide 1. Twelve groups were created from 120 mice: Negative Control, cyclophosphamide (100 mg/kg), cisplatin (6 mg/kg), Phthalide 1 (5, 10 and 20 mg/kg), and associations of 1 with cyclophosphamide and 1 with cisplatin. The results demonstrate that 1 increases (p 1 with cyclophosphamide and cisplatin demonstrated a chemopreventive effect and, therefore, a reduction (p 1 has potential chemotherapeutic application and may be a candidate for developing a new generation of chemotherapeutics. In addition, it has characteristics to be used as a chemotherapy adjuvant in association with cyclophosphamide and cisplatin since it increases the frequency of cell death induced by chemotherapy. We also reported that the chemopreventive effect of 1, in association with cyclophosphamide and cisplatin, can prevent adverse effects (induction of DNA damage in non-tumor cells) without interfering with the mode of action of chemotherapy drugs and, therefore, without reducing the induction of cell death.
