Evaluation of the Antitumor Potential of the Resorcinolic Lipid 3-Heptyl-3,4,6-trimethoxy-3H-isobenzofuran-1-one in Breast Cancer Cells

Rabacow, Ana Paula Maluf; Meza, Alisson; Oliveira, Edwin José Torres de; David, Natan de; Vitor, Neimar; Antoniolli-Silva, Andréia Conceição Milan Brochado; Matos, Maria de Fátima Cepa; Perdomo, Renata Trentim; Gomes, Roberto da Silva; Lima, Dênis Pires de; Beatriz, Adilson; Oliveira, Rodrigo Juliano

doi:10.21873/anticanres.12761

Cited by 8 publications

(6 citation statements)

References 18 publications

(35 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The literature indicates that cell death induced by resorcinol lipids may be mediated by the Nur77 nuclear orphan receptor [ 19 , 20 ] or DNA damage [ 2 , 4 ].…”

Section: Discussionmentioning

confidence: 99%

“…Resorcinolic lipids, such as cytosporones and their precursors, can interact with the phospholipid bilayers [ 1 ], help in the formation of liposomes [ 2 ], promote protection against oxidative stress [ 3 ], and inhibit bacterial growth [ 1 , 2 ] and tumor cells [ 4 ]. In addition, the resorcinol lipid cytosporone B induced apoptosis in tumor cells by interacting with the nuclear orphan receptor Nur77 [ 2 , 4 ]. This fact led different research groups to dedicate themselves to describing the possible chemotherapeutic effects of precursors and cytosporones.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

3-Heptylidene-4,6-Dimethoxy-3H-Isobenzofuran-1-One Is Genotoxic, Increases the Frequency of Cell Death, and Potentiates the Effects of Cyclophosphamide and Cisplatin

et al. 2023

Self Cite

View full text Add to dashboard Cite

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 < 0.05) the frequency of chromosomal damage, liver and kidney cell death, and splenic phagocytosis. The association of 1 with cyclophosphamide and cisplatin demonstrated a chemopreventive effect and, therefore, a reduction (p < 0.05) in the frequency of chromosomal damage. However, cell death and splenic phagocytosis did not suffer significant variations. As a result of the above, 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.

show abstract

“…The literature indicates that cell death induced by resorcinol lipids may be mediated by the Nur77 nuclear orphan receptor [ 19 , 20 ] or DNA damage [ 2 , 4 ].…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

3-Heptylidene-4,6-Dimethoxy-3H-Isobenzofuran-1-One Is Genotoxic, Increases the Frequency of Cell Death, and Potentiates the Effects of Cyclophosphamide and Cisplatin

et al. 2023

Self Cite

View full text Add to dashboard Cite

show abstract

“…All differences were considered significant when p≤0.05 (GraphPad InStat 5 software). The qPCR was analyzed through the REST program (Pfaffl et al, 2002), was considered significant difference, when the level of relative expression was p≤ 0.5 or higher than 2 (Biazi et al, 2017;Navarro et al, 2018;Rabacow et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

The treatment with all-trans retinoic acid causes apoptosis without chromosomal instability in adipose-derived stem cells and might act starting the browning process

Schweich-Adami

Antoniolli-Silva

Oliveira

2022

RSD

Self Cite

View full text Add to dashboard Cite

Introduction: The knowledge about the biology of obesity and apoptosis induction of adipose-derived stem cells (ADSCs) may support in the development of new therapies. Objective: The present research aimed to investigate the toxicogenic effect of all-trans retinoic acid (ATRA) as well as its influence in the adipogenic differentiation and expression of genes related to DNA damage, cell cycle and thermogenesis. Methodology: Cell cultures of human adipose-derived stem cells were treated for 12 hours with ATRA (20.75 μM) and were performed the adipogenic differentiation, comet assay, micronucleous, cell death, cell cycle and qPCR. Results: The ATRA treatment decreased the capacity of adipogenic differentiation of ADSCs. The comet assay demonstrated increase in nucleoid frequency with genomic damage and scoring. However, these damages were not fixed at the chromosome level, since the tail moment was not significant. The treatment with ATRA increased cytotoxicity and increased cell death by apoptosis. The relative expression of CHEK-1, CHEK-2, CDC25A, CDC25C, ATM and ATR decreased and only UCP1 increased significantly. Conclusion: The results of the present study demonstrate that the use of ATRA induces genomic damage in ADSCs, although it was eliminated in the apoptosis process. Therefore, administration of ATRA in ADSCs did not cause chromosomal instability, which suggests toxicogenic safety. Also it was considered that ATRA might active the browning effect. Thus, this compound is considered a promising candidate for the development of novel therapies for the treatment of obesity and / or localized fat by the use of mesotherapy.

show abstract

“…Isobenzofuran, isobenzofuran-1(3H)-one and 3-hydroxyisobenzofuran-1(3H)-one heterocycle rings are structural motifs building up important pharmaceuticals and naturally occurring substances evidenced to have plausible radical scavenging potential [11]. These have been shown to possess bunch of therapeutic properties, such as anti-tumour [12,13], anti-diabetic [14,15], antimycotic [16], antibacterial [17][18][19][20], cytotoxic [17,19,21] and antioxidative [15,16,18,20,[22][23][24][25][26]. Fungi provide virtually endless natural source of that class of compounds [16,[27][28][29][30], with many of them already being successfully used, as for example griseofulvin.…”

Section: Introductionmentioning

confidence: 99%

Natural dihydroisobenzofuran derivatives as a template for promising radical scavengers: theoretical insights into structure–activity relationships, thermochemistry and kinetics

Spiegel

Sroka

2022

Theor Chem Acc

View full text Add to dashboard Cite

Dihydroisobenzofuran heterocycle is a structural motif found in a number of medications with anti-tumour, anti-diabetic, and antibacterial activities. It is also found in a slew of natural substances, most notably fungus metabolites, which have been shown to possess credible radical scavenging activity. Density functional theory studies on three different derivatives were conducted to investigate their electronic structures as well as thermochemical and kinetic behaviour against ·OOH, ·OH, and ·OCH3 in biologically relevant solvents, with the goal of elucidating structure–activity relationships and discussing the potential role of the scaffolds as a template for new semisynthetic antioxidants. The importance of resonance and inductive effects, and also hydrogen bonding, has been underlined, but most importantly, it has been demonstrated that all structures have considerable scavenging potential against all studied radicals, with reactions rates close to the diffusion limit.

show abstract

Evaluation of the Antitumor Potential of the Resorcinolic Lipid 3-Heptyl-3,4,6-trimethoxy-3H-isobenzofuran-1-one in Breast Cancer Cells

Abstract: AMS35AA has potential for breast cancer treatment since it is capable of exerting cytotoxic and cytostatic effects in a breast cell line and also could be an adjuvant in cancer therapy when combined with 5-FU.

Cited by 8 publications

References 18 publications

3-Heptylidene-4,6-Dimethoxy-3H-Isobenzofuran-1-One Is Genotoxic, Increases the Frequency of Cell Death, and Potentiates the Effects of Cyclophosphamide and Cisplatin

3-Heptylidene-4,6-Dimethoxy-3H-Isobenzofuran-1-One Is Genotoxic, Increases the Frequency of Cell Death, and Potentiates the Effects of Cyclophosphamide and Cisplatin

The treatment with all-trans retinoic acid causes apoptosis without chromosomal instability in adipose-derived stem cells and might act starting the browning process

Natural dihydroisobenzofuran derivatives as a template for promising radical scavengers: theoretical insights into structure–activity relationships, thermochemistry and kinetics

Contact Info

Product

Resources

About