Modulating effect of DL-kavain on the mutagenicity and carcinogenicity induced by doxorubicin in <i>Drosophila melanogaster</i>

Silva, Thaís Teixeira da; Martins, Júlia Braga; Lopes, Maria Do Socorro de Brito; Almeida, Pedro Marcos de; Sá, José Luiz Silva; Martins, Francielle Alline

doi:10.1080/15287394.2021.1942354

Cited by 13 publications

(4 citation statements)

References 77 publications

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“…Ruxolitinib is the inhibitor of Janus kinase 2 (JAK2), which can synergistically induce cell apoptosis with cisplatin, and is promising to provide a method to treat CC patients [ 54 ]. In the epithelial tumor test (ETT) on black fruit flies, kavain bound to the chemotherapeutic doxorubicin (DXR) to synergistically induce the enhanced carcinogenic effect of DXR on tumor [ 55 ]. These predicted drugs have high reliability and are related to cancer treatment.…”

Section: Discussionmentioning

confidence: 99%

CircRNA-Based Cervical Cancer Prognosis Model, Immunological Validation and Drug Prediction

et al. 2022

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Background: Cervical cancer (CC) is a common cancer in female, which is associated with problems like poor prognosis. Circular RNA (circRNA) is a kind of competing endogenous RNA (ceRNA) that has an important role in regulating microRNA (miRNA) in many cancers. The regulatory mechanisms of CC immune microenvironment and the transcriptome level remain to be fully explored. Methods: In this study, we constructed the ceRNA network through the interaction data and expression matrix of circRNA, miRNA and mRNA. Meanwhile, based on the gene expression matrix, CIBERSORT algorithm was used to reveal contents of tumor-infiltrating immune cells (TIICs). Then, we screened prognostic markers based on ceRNA network and immune infiltration and constructed two nomograms. In order to find immunological differences between the high- and low-risk CC samples, we examined multiple immune checkpoints and predicted the effect of PD-L1 ICI immunotherapy. In addition, the sensitive therapeutics for high-risk patients were screened, and the potential agents with anti-CC activity were predicted by Connective Map (CMap). Results: We mapped a ceRNA network including 5 circRNAs, 17 miRNAs and 129 mRNAs. From the mRNA nodes of the network six genes and two kind of cells were identified as prognostic makers for CC. Among them, there was a significant positive correlation between CD8+ T cells and SNX10 gene. The results of TIDE and single sample GSEA (ssGSEA) showed that T cells CD8 do play a key role in inhibiting tumor progression. Further, our study screened 24 drugs that were more sensitive to high-risk CC patients and several potential therapeutic agents for reference. Conclusions: Our study identified several circRNA-miRNA-mRNA regulatory axes and six prognostic genes based on the ceRNA network. In addition, through TIIC, survival analysis and a series of immunological analyses, T cells were proved to be good prognostic markers, besides play an important role in the immune process. Finally, we screened 24 potentially more effective drugs and multiple potential drug compounds for high- and low-risk patients.

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Section: Discussionmentioning

confidence: 99%

CircRNA-Based Cervical Cancer Prognosis Model, Immunological Validation and Drug Prediction

et al. 2022

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“…Chromosomal mutations or aberrations affect oncogenes and tumor suppressor genes leading to the malignant transformation [48,97]. Thus, genomic instability is associated with serious pathological disorders such as cancer [44,48,[98][99][100][101]. In addition, CEAC induces apoptosis of damaged cells during the embryonic development of the larvae, with consequent reduction of tumors in adults.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, we also suggest that, in the post-treatment, the anticarcinogenic effect of CEAC is due to the increased activity of proteins involved in repair pathways related to the tumor suppressor gene Warts, which promoted the control of cell proliferation and reduction of the formation of epithelial tumors. Importantly, we use the ETT test that assesses the toxicity, mutagenicity and carcinogenicity of different compounds [98,[102][103][104][105], based on phenotypic effects. However, it has been shown that aqueous and ethanolic extracts of A. chica inhibit inflammatory and angiogenic processes [89,106,107] and that its ethanolic extract also reduces the lipid oxidative stress marker malondialdehyde [67,108].…”

Section: Discussionmentioning

confidence: 99%

Arrabidaea chica chloroform extract modulates estrogen and androgen receptors on luminal breast cancer cells

Brandão

Lima

Martins

et al. 2022

BMC Complement Med Ther

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Background Breast Cancer (BC) is the most common cancer in women worldwide and, although 70% of patients are responsive to selective Estrogen Receptor (ER) modulators such as Tamoxifen (Tam), patients’ survival is comprised by resistance to endocrine therapy. Brazilian flora, especially the Amazon biome, is one of the richest global sources of native species with potentially bioactive compounds. Arrabidaea chica is a plant native to the Amazon that has been used in the treatment of different diseases. However, its action on BC remains unclear. Methods Herein the biological effects of the chloroform extract of A. chica (CEAC) were evaluated on BC cells and in in vivo model. After confirmation of CEAC antioxidant capacity, cells were treated with CEAC and Tam, alone and with CEAC+Tam. The cell viability was evaluated by MTT and hormone receptor transcripts levels were assessed (ESR1, ESR2 and AR). Finally, anticarcinogenicity of CEAC was recorded in Drosophila melanogaster through Epithelial Tumor Test (ETT). Results The study confirmed the antioxidant activity of CEAC. CEAC was selective for MCF-7, downregulating ESR2 and AR transcripts and upregulating ESR2 expression. The modulatory effects of CEAC on ERs did not differ between cells treated with Tam and with CEAC+Tam. Interestingly, previous treatment with CEAC, followed by treatment with Tam promoted a significant decrease in cell viability. The extract also presented anticarcinogenic effect in in vivo assay. Conclusion The bioassays on breast tumor cells demonstrated the antiproliferative activity of the extract, which modulated the expression of hormone receptors and sensitized luminal tumor cells to Tam. These results suggest that CEAC could be a complementary treatment for BC.

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“…NTP also reported negative results in the in vivo micronucleus assay performed with B6C3F mice (male and female) treated with kava extracts for 3 months [ 5 ]. Recently, the mutagenic and carcinogenic potential of kavain and its combined effect with doxorubicin (Dox) was assessed in the Drosophila melanogaster model [ 78 ]. In the crosses with basal CYP450 metabolism, kavain was not mutagenic in the Somatic Mutation and Recombination Test (SMART).…”

Section: Kava-induced Toxicity and Safety Issuesmentioning

confidence: 99%

An Updated Review on the Psychoactive, Toxic and Anticancer Properties of Kava

Soares

Dinis-Oliveira

Oliveira

2022

JCM

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Kava (Piper methysticum) has been widely consumed for many years in the South Pacific Islands and displays psychoactive properties, especially soothing and calming effects. This plant has been used in Western countries as a natural anxiolytic in recent decades. Kava has also been used to treat symptoms associated with depression, menopause, insomnia, and convulsions, among others. Along with its putative beneficial health effects, kava has been associated with liver injury and other toxic effects, including skin toxicity in heavy consumers, possibly related to its metabolic profile or interference in the metabolism of other xenobiotics. Kava extracts and kavalactones generally displayed negative results in genetic toxicology assays although there is sufficient evidence for carcinogenicity in experimental animals, most likely through a non-genotoxic mode of action. Nevertheless, the chemotherapeutic/chemopreventive potential of kava against cancer has also been suggested. Both in vitro and in vivo studies have evaluated the effects of flavokavains, kavalactones and/or kava extracts in different cancer models, showing the induction of apoptosis, cell cycle arrest and other antiproliferative effects in several types of cancer, including breast, prostate, bladder, and lung. Overall, in this scoping review, several aspects of kava efficacy and safety are discussed and some pertinent issues related to kava consumption are identified.

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Modulating effect of DL-kavain on the mutagenicity and carcinogenicity induced by doxorubicin in Drosophila melanogaster

Cited by 13 publications

References 77 publications

CircRNA-Based Cervical Cancer Prognosis Model, Immunological Validation and Drug Prediction

CircRNA-Based Cervical Cancer Prognosis Model, Immunological Validation and Drug Prediction

Arrabidaea chica chloroform extract modulates estrogen and androgen receptors on luminal breast cancer cells

An Updated Review on the Psychoactive, Toxic and Anticancer Properties of Kava

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