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1.
Toxicol In Vitro ; 93: 105669, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37634662

RESUMO

Thyroid cancer is one of the most common endocrine malignancies. Differentiated thyroid cancer (DTC) treatment is based on the ability of thyroid follicular cells to accumulate radioactive iodide (RAI). DTC generally has a good prognosis. However, tumor dedifferentiation or defect in certain cell death mechanism occurs in a subset of DTC patients, leading to RAI resistance. Therefore, developing novel therapeutic approaches that enhance RAI sensitivity are still warranted. We found that curcumin, an active ingredient in turmeric with anti-cancer properties, rapidly accumulated in the mitochondria of thyroid cancer cells but not normal epithelial cells. Curcumin treatment triggered mitochondrial membrane depolarization, engulfment of mitochondria within autophagosomes and a robust decrease in mitochondrial mass and proteins, indicating that curcumin selectively induced mitophagy in thyroid cancer cells. In addition, curcumin-induced mitophagic cell death and its synergistic cytotoxic effect with radioiodine could be attenuated by autophagy inhibitor, 3-methyladenine (3-MA). Interestingly, the mechanism of mitophagy-inducing potential of curcumin was its unique mitochondria-targeting property, which induced a burst of SDH activity and excessive ROS production. Our data suggest that curcumin induces mitochondrial dysfunction and triggers lethal mitophagy, which synergizes with radioiodine to kill thyroid cancer cells.


Assuntos
Curcumina , Neoplasias da Glândula Tireoide , Humanos , Câncer Papilífero da Tireoide/tratamento farmacológico , Curcumina/farmacologia , Radioisótopos do Iodo , Succinato Desidrogenase/metabolismo , Mitofagia , Linhagem Celular Tumoral , Neoplasias da Glândula Tireoide/radioterapia , Neoplasias da Glândula Tireoide/tratamento farmacológico , Mitocôndrias/metabolismo
2.
Plant Dis ; 107(10): 3264-3268, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36935384

RESUMO

Elsinoë annonae is a fungal pathogen that causes fruit scab disease in the edible-oil (tea oil) plant (Camellia oleifera Abel). The absence of genome resources for this fungus hampers functional genetic studies of the pathogenesis mechanism of E. annonae. This study reports the genome assembly of E. annonae strain SM-YC-2 collected from tea oil tree fruit with scab disease in Fujian Province, China. Combining 16.44 Gb of PacBio Sequel II long reads and 5.13 Gb of Illumina NovaSeq reads, we generated a 25.93-Mb (99.19% of expected genome size) high-quality genome assembly with 52.66% GC content, 5.05% repeats, and over 98% Benchmarking Universal Single-Copy Orthologs completeness for E. annonae strain SM-YC-2. These high-quality genome assembly resources will facilitate functional genomic characterization studies, enhance insights into the pathogenicity mechanism of E. annonae, and support the development of molecular-based control strategies.


Assuntos
Camellia , Camellia/genética , Frutas , Genômica , Chá
3.
Phytother Res ; 36(2): 938-950, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35076979

RESUMO

Capsaicin (CAP) is a well-known anti-cancer agent. Recently, we reported capsaicin-induced apoptosis in anaplastic thyroid cancer (ATC) cells. It is well accepted that the generation of cancer stem cells (CSCs) is responsible for the dedifferentiation of ATC, the most lethal subtype of thyroid cancer with highly dedifferentiation status. Whether CAP inhibited the ATC growth through targeting CSCs needed further investigation. In the present study, CAP was found to induce autophagy in ATC cells through TRPV1 activation and subsequent calcium influx. Meanwhile, CAP dose-dependently decreased the sphere formation capacity of ATC cells. The stemness-inhibitory effect of CAP was further by extreme limiting dilution analysis (ELDA). CAP significantly decreased the protein level of OCT4A in both 8505C and FRO cells. Furthermore, CAP-induced OCT4A degradation was reversed by autophagy inhibitors 3-MA and chloroquine, BAPTA-AM and capsazepine, but not proteasome inhibitor MG132. Collectively, our study firstly showed CAP suppressed the stemness of ATC cells partially via calcium-dependent autophagic degradation of OCT4A. Our study lent credence to the feasible application of capsaicin in limiting ATC stemness.


Assuntos
Carcinoma Anaplásico da Tireoide , Neoplasias da Glândula Tireoide , Apoptose , Autofagia , Capsaicina/farmacologia , Linhagem Celular Tumoral , Humanos , Lisossomos , Carcinoma Anaplásico da Tireoide/tratamento farmacológico , Carcinoma Anaplásico da Tireoide/patologia , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/patologia
4.
Plant Dis ; 105(11): 3723-3726, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33978433

RESUMO

Tea gray blight is one of the most serious foliar diseases of tea tree, caused by the plant-pathogenic fungus Pseudopestalotiopsis theae, which can affect production and quality of tea worldwide. We generated a highly contiguous, 50.41-Mbp genome assembly (N50 = 1.30 Mbp) of P. theae strain CYF27 by combining PacBio long-read and Illumina short-read sequencing technologies. We identified a total of 15,626 gene models, of which 1,038 genes encode putative secreted proteins. The high-quality genome assembly and annotation resource reported here will be useful for the study of fungal infection mechanisms and pathogen-host interaction.


Assuntos
Ascomicetos , Doenças das Plantas , Ascomicetos/genética , Análise de Sequência de DNA , Chá
5.
Phytother Res ; 35(6): 3428-3443, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33751676

RESUMO

It is widely accepted that anaplastic thyroid carcinoma (ATC), a rare, extremely aggressive malignant, is enriched by cancer stem cells (CSCs), which are closely related to the pathogenesis of ATC. In the present study, we demonstrated that diallyl trisulphide (DATS), a well-known hydrogen sulphide (H2 S) donor, suppressed sphere formation and restored the expression of iodide-metabolizing genes in human ATC cells, which were associated with H2 S generation. Two other H2 S donors, NaHS and GYY4137, could also suppress the self-renewal properties of ATC cells in vitro. Compared with normal thyroid tissues and papillary thyroid carcinomas (PTCs), the elevated expressions of SOX2 and MYC, two cancer stem cell markers, in ATCs were validated in the combined Gene Expression Omnibus (GEO) cohort. DATS decreased the expression of SOX2, which was mediated by H2 S generation. Furthermore, knockdown of AKT or inhibition of AKT by DATS led to a decrease of SOX2 expression in ATC cells. AKT knockdown phenocopied restoration of thyroid-specific gene expression in ATC cells. Our data suggest that H2 S donors treatment can compromise the stem cell phenotype and restore thyroid-specific gene expression of ATC cells by targeting AKT-SOX2 pathway, which may serve as a therapeutic strategy to intervene the CSC progression of ATC.


Assuntos
Compostos Alílicos/farmacologia , Sulfetos/farmacologia , Carcinoma Anaplásico da Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/tratamento farmacológico , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Humanos , Células-Tronco Neoplásicas/patologia , Fenótipo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fatores de Transcrição SOXB1/metabolismo , Câncer Papilífero da Tireoide/tratamento farmacológico , Carcinoma Anaplásico da Tireoide/genética , Carcinoma Anaplásico da Tireoide/patologia , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/patologia
6.
Mol Plant Microbe Interact ; 33(12): 1438-1440, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32924760

RESUMO

Ascochyta versabilis is the fungal pathogen that causes the severe leaf spot disease of Pseudostellaria heterophylla (Miq.) Pax, a vital Chinese herbal plant. Here, we deployed PacBio single-molecule real-time long-read sequencing technology to generate a near-complete genome assembly for the A. versabilis KC1 strain and obtained a total of 9.80 Gb raw reads. These reads were processed into a 41.05 Mb genome assembly containing 95 contigs with N50 of 1.70 Mb and a maximum length of 3.93 Mb. A total of 10,457 gene models, of which 1,004 encode putatively secreted proteins, were identified in the genome. This high-quality genome assembly and gene annotation resource will facilitate the institution of functional genetic studies aimed at providing a better insight into the infection mechanisms of A. versabilis to support the development of effective control strategies for leaf spot disease of P. heterophylla.


Assuntos
Ascomicetos , Genoma Fúngico , Ascomicetos/genética , Caryophyllaceae/microbiologia , Genoma Fúngico/genética , Doenças das Plantas/microbiologia
7.
Phytother Res ; 34(5): 1154-1165, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31984539

RESUMO

Diallyl trisulfide (DATS), derived from garlic, is a well-known hydrogen sulfide (H2 S) donor. H2 S has recently emerged as a novel gasotransmitter involved in the regulation of cancer progression. The present study demonstrated that DATS along with other two H2 S donors, NaHS and GYY4137, significantly inhibited papillary thyroid carcinoma KTC-1 cells growth. DATS treatment triggered a rapid H2 S generation within 5 min in KTC-1 cells. Iodoacetamide, a potent thiol blocker reagent, partially rescued the cell membrane damage and ultimate cell death induced by DATS, indicating H2 S contributed to the apoptosis-inducing efficacy of DATS on thyroid cancer cells. Specifically, DATS treatment significantly upregulated the expression and enzymatic activity of cystathionine gamma-lyase (CTH), one of H2 S-producing enzymes, which was responsible for endogenous H2 S generation. After DATS treatment, H2 S quickly permeated cell membranes and activated NF-κΒ/p65 signaling pathway in KTC-1 cells. Nuclear translocated NF-κB bound to the promoter of CTH to enhance its transcription. These evidences proved that exogenous H2 S elevated CTH expression. CTH, in turn, catalytically generated a much higher level of endogenous H2 S. This positive feedback sustained excess H2 S production, which resulted in PTC cells growth inhibition. These findings may shed light on the development of novel H2 S-based antitumor agents.


Assuntos
Compostos Alílicos/uso terapêutico , Cistationina gama-Liase/efeitos dos fármacos , Inibidores da Agregação Plaquetária/uso terapêutico , Sulfetos/uso terapêutico , Câncer Papilífero da Tireoide/tratamento farmacológico , Compostos Alílicos/farmacologia , Linhagem Celular Tumoral , Humanos , Inibidores da Agregação Plaquetária/farmacologia , Sulfetos/farmacologia
8.
J Agric Food Chem ; 66(23): 5871-5878, 2018 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-29786427

RESUMO

This study aimed to elucidate the potential effects of diallyl trisulfide (DATS) on human papillary-thyroid-carcinoma BCPAP cells and its underlying mechanisms. DATS is an organosulfur compound derived from garlic. In this study, we demonstrated that compared with the solvent control, DATS treatment at concentrations of 5, 10, and 20 µΜ decreased cell survival rates of BCPAP cells to 84.51 ± 2.67, 57.16 ± 1.18, and 41.22 ± 1.19% respectively. DATS also caused cell-cycle arrest at G0/G1 phase, and the proportion of cells arrested in G0/G1 phase rose from 68.8 ± 8.38 to 80.4 ± 8.38%, which eventually resulted in cell apoptosis through a mitochondrial apoptotic pathway in BCPAP cells. Further evidence showed that DATS activated ERK, JNK, and p38, members of the MAPK family. Moreover, ERK and JNK inhibitors partially reversed apoptosis in BCPAP cells induced by DATS treatment. Taken together, our results demonstrated that DATS exerted an apoptosis-inducing effect on papillary-thyroid-cancer cells via activation of the MAPK signaling pathway, which shed light on a prospective therapeutic target for thyroid-cancer treatment.


Assuntos
Compostos Alílicos/farmacologia , Apoptose/efeitos dos fármacos , Carcinoma Papilar/patologia , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Transdução de Sinais/efeitos dos fármacos , Sulfetos/farmacologia , Neoplasias da Glândula Tireoide/patologia , Antineoplásicos Fitogênicos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Alho/química , Humanos , Mitocôndrias/efeitos dos fármacos , Câncer Papilífero da Tireoide
9.
Food Chem ; 132(1): 43-50, 2012 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-26434261

RESUMO

Recently, many studies on health benefits associated with curcumin have been reported. In this study, the effects of curcumin on apoptosis of papillary thyroid cancer cell line K1 and its potential mechanisms were investigated. Curcumin was found to significantly inhibit cell viability and promoted cell apoptosis in a dose-dependent manner. Moreover, curcumin-induced cell apoptosis was characterized with a rapid stimulation of reactive oxygen species (ROS) production. Furthermore, curcumin-induced ROS generation led to the loss of mitochondrial membrane potential (MMP) and the disturbance of intracellular Ca(2+) concentration. A decrease in expression of Bcl-2 and the cleavage of poly ADP-ribose polymerase (PARP) were observed after exposure to curcumin. Results of this study may elucidate the curcumin-induced apoptosis effects on K1 cells. Thus, our results indicate a role of curcumin as health-promoting food ingredient, as well as a potential chemotherapeutic agent which is able to fight against papillary thyroid cancer.


Assuntos
Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Carcinoma/tratamento farmacológico , Curcumina/uso terapêutico , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Neoplasias da Glândula Tireoide/tratamento farmacológico , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia , Carcinoma Papilar , Curcumina/administração & dosagem , Curcumina/farmacologia , Humanos , Câncer Papilífero da Tireoide
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