Upregulation of apoptotic protease activating factor-1 expression correlates with anti-tumor effect of taxane drug

Bakhshoudeh, Meysam; Mehdizadeh, Kayhan; Hosseinkhani, Saman; Ataei, Farangis

doi:10.1007/s12032-021-01532-8

Cited by 9 publications

(3 citation statements)

References 42 publications

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“…Interestingly, our findings are consistent with other studies. Previous research found that MCF7 cells transfected with APAF1 were more sensitive to Docetaxel due to increasing the mitochondrial permeability for cytochrome c release, which promoted apoptosome formation and intrinsic apoptosis [ 93 ]. Taken together, inducing the expression of BCL10 and APF1 in TNBC cells could be partly responsible for TQ’s apoptotic effects.…”

Section: Discussionmentioning

confidence: 99%

Thymoquinone Alterations of the Apoptotic Gene Expressions and Cell Cycle Arrest in Genetically Distinct Triple-Negative Breast Cancer Cells

et al. 2022

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Breast cancer (BC) is the most common cancer in women worldwide, and it is one of the leading causes of cancer death in women. triple-negative breast Cancer (TNBC), a subtype of BC, is typically associated with the highest pathogenic grade and incidence in premenopausal and young African American (AA) women. Chemotherapy, the most common treatment for TNBC today, can lead to acquired resistance and ineffective treatment. Therefore, novel therapeutic approaches are needed to combat medication resistance and ineffectiveness in TNBC patients. Thymoquinone (TQ) is shown to have a cytotoxic effect on human cancer cells in vitro. However, TQ’s mode of action and precise mechanism in TNBC disease in vitro have not been adequately investigated. Therefore, TQ’s effects on the genetically different MDA-MB-468 and MDA-MB-231 human breast cancer cell lines were assessed. The data obtained show that TQ displayed cytotoxic effects on MDA-MB-468 and MDA-MB-231 cells in a time- and concentration-dependent manner after 24 h, with IC50 values of 25.37 µM and 27.39 µM, respectively. Moreover, MDA-MB-231 and MDA-MB-468 cells in a scratched wound-healing assay displayed poor wound closure, inhibiting invasion and migration via cell cycle blocking after 24 h. TQ arrested the cell cycle phase in MDA-MB-231 and MDA-MB-468 cells. The three cell cycle stages in MDA-MB-468 cells were significantly affected at 15 and 20 µM for G0/G1 and S phases, as well as all TQ concentrations for G2/M phases. In MDA-MB-468 cells, there was a significant decrease in G0/G1 phases with a substantial increase in the S phase and G2/M phases. In contrast, MDA-MB-231 showed a significant effect only during the two cell cycle stages (S and G2/M), at concentrations of 15 and 20 µM for S phases and all TQ values for G2/M phases. The TQ effect on the apoptotic gene profiles indicated that TQ upregulated 15 apoptotic genes in MDA-MB-231 TNBC cells, including caspases, GADD45A, TP53, DFFA, DIABLO, BNIP3, TRAF2/3, and TNFRSF10A. In MDA-MB-468 cells, 16 apoptotic genes were upregulated, including TNFRSF10A, TNF, TNFRSF11B, FADD TNFRSF10B, CASP2, and TRAF2, all of which are important for the apoptotic pathway andsuppress the expression of one anti-apoptotic gene, BIRC5, in MDA-MB-231 cells. Compared to MDA-MB-231 cells, elevated levels of TNF and their receptor proteins may contribute to their increased sensitivity to TQ-induced apoptosis. It was concluded from this study that TQ targets the MDA-MB-231 and MDA-MB-468 cells differently. Additionally, due to the aggressive nature of TNBC and the lack of specific therapies in chemoresistant TNBC, our findings related to the identified apoptotic gene profile may point to TQ as a potential agent for TNBC therapy.

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Section: Discussionmentioning

confidence: 99%

Thymoquinone Alterations of the Apoptotic Gene Expressions and Cell Cycle Arrest in Genetically Distinct Triple-Negative Breast Cancer Cells

et al. 2022

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“…APAF1 plays an important role in apoptosis, since it is essential for apoptosome formation. The in vivo loss of APAF-1 expression is generally associated with tumor progression [43] and its up-regulation is associated with the antitumor activity of taxane [44]. S100 calcium binding protein A7A (S100A7), also known as psoriasin, has been found to be up-regulated in CM-treated cells.…”

Section: Mechanism Of Action Of Fraction C Of Ctoa and Cmmentioning

confidence: 99%

Jellyfish as an Alternative Source of Bioactive Antiproliferative Compounds

et al. 2022

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Jellyfish are commonly considered a nuisance for their negative effects on human activities (e.g., fisheries, power plants and tourism) and human health. However, jellyfish provide several benefits to humans and are commonly eaten in eastern countries. Additionally, recent studies have suggested that jellyfish may become a source of high-value molecules. In this study, we tested the effects of the methanolic extracts and enriched fractions, obtained by solid-phase extraction fractionation, from the scyphomedusae Pelagia noctiluca, Rhizostoma pulmo, Cotylorhiza tuberculata and the cubomedusa Caryddea marsupialis on different human cancer cell lines in order to evaluate a potential antiproliferative activity. Our results indicated that fraction C from Caryddea marsupialis-(CM) and C. tuberculata oral arms (CTOA) were the most active to reduce cell viability in a dose-dependent manner. LC/MS based dereplication analyses highlighted that both bioactive fractions contained mainly fatty acids and derivatives, with CM additionally containing small peptides (0.7–0.8 kDa), which might contribute to its higher biological activity. The mechanism of action behind the most active fraction was investigated using PCR arrays. Results showed that the fraction C of CM can reduce the expression of genes involved in apoptosis inhibition in melanoma-treated cells, which makes jellyfish a potential new source of antiproliferative drugs to be exploited in the future.

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“…Apoptozun temel olarak kaspazlar ve Bcl2 ailesi üyeleri tarafından düzenlendiği bilinmektedir (8) (10). Bu genin ekspresyon azalışının meme kanseri hücrelerinde apoptoz inhibisyonu ve ilaç direnci ile ilişkili olabileceği önerilmiştir (11). Çalışmamızda APAF1 geninin ekspresyonu dört hücre hattında da anlamlı şekilde azalmıştır (kat düzenlenmesi ≥ ±2,00; p < 0,05).…”

Section: Bulgular Apoptoz Apoptotik Uyaranın Ortadan Kaldırılmasıyla ...unclassified

Identification of the phenomenon of anastasis in breast cancer cells

Bağca

2022

Ege Tıp Dergisi

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Aim: This study aimed to define the expression changes and potential roles of the apoptosis-related genes in the anastasis process in breast cancer, which is one of the most common cancer types. Materials and Methods: Different types of breast cancer cell lines (MCF7 and MDA-MB-231), breast cancer stem cells, and healthy breast cell line (MCF10A) were used. Apoptotic and anastatic cell percentages were determined by the Annexin V test and flow cytometry. Gene expression changes in anastatic cells compared to apoptotic cells were determined by the qRT-PCR and 2-ΔΔCt method. The pathways and biological processes of genes that show significant changes were determined using the STRING v11.5 database. Results: In all cell groups, it was determined that the percentage of apoptosis increased as a result of ethanol application, and the percentage of apoptotic cells decreased with the removal of the apoptosis-inducing factor. The change in the percentage of apoptotic cells between the control, apoptosis, and anastasis groups was determined the most in MCF7 cells. Consistently, expression changes were determined in the largest number of genes in this cell line. CASP7 and APAF1 genes downregulated in all cell lines. In all cell groups, it was determined that anastasis affects Cysteine-type endopeptidase activity involved in execution phase of apoptosis (GO_ID: 0043027), and drug resistance-related pathways (KEGG_ID: hsa01524). Conclusion: The definition of the interaction of the anastasis phenomenon in cells with apoptosis regulatory mechanisms is important in terms of elucidating both the oncogenic transformation of healthy cells and the mechanisms of drug resistance in cancer.

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Upregulation of apoptotic protease activating factor-1 expression correlates with anti-tumor effect of taxane drug

Cited by 9 publications

References 42 publications

Thymoquinone Alterations of the Apoptotic Gene Expressions and Cell Cycle Arrest in Genetically Distinct Triple-Negative Breast Cancer Cells

Thymoquinone Alterations of the Apoptotic Gene Expressions and Cell Cycle Arrest in Genetically Distinct Triple-Negative Breast Cancer Cells

Jellyfish as an Alternative Source of Bioactive Antiproliferative Compounds

Identification of the phenomenon of anastasis in breast cancer cells

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