Search

Introduction: Cancer is the second leading cause of death globally, and among all types of cancer, triple-negative breast cancer (TNBC) has one of the worst prognoses. The repeated use of chemotherapeutic drugs often leads to drug resistance, complicating treatment outcomes. This study aimed to investigate the effect of jujube alkaloid-rich extract on drug sensitivity and its antitumor effects on paclitaxel-resistant MDA-MB-231 cells in vitro. Materials and methods: This study utilized the MDA-MB-231 breast cancer cell line and its paclitaxel-resistant variant. Cell viability was measured using the XTT assay, while apoptosis was detected through Annexin-PI assays. Various concentrations of jujube extract, alone and combined with paclitaxel, were assessed for synergistic effects in 2D and 3D culture models. Results: The presence of alkaloids in the jujube seed extract was confirmed via the Dragendorff test, with 0.395 g of alkaloids present in 5 g of jujube seed powder. A combination of paclitaxel and jujube extract exhibited dose-dependent cytotoxic effects on paclitaxel-resistant MDA-MB-231 cells. The combination of jujube extract and paclitaxel significantly decreased IC50 from 541.3 μg/ml to 124.3 μg/ml, and the IC20 decreased from 92.1 μg/ml to 23.9 μg/ml when combined with paclitaxel in 2D culture model. The cytotoxicity of the combination was reduced in the 3D culture model. Apoptosis rates were 0.75% in the control group, 13.89% in the alkaloid-rich extract group, 2.59% in the paclitaxel group, and 42.90% in the combination group. Conclusion: Combining alkaloid-rich jujube seed extract with paclitaxel regenerates the cytotoxicity and apoptotic ability of paclitaxel in the paclitaxel-resistant MDA-MB-231 breast cancer cells in both 2D and 3D culture models. This suggests that such combinations might be a viable strategy to overcome drug resistance in TNBC treatments.

A novel class of chalcones were synthesized via the Claisen-Schmidt condensation of 6-chloropyridine-3-carbaldhyde with various ortho, meta, and para substituted acetophenones in the presence of a base and a polar protic solvent. The newly synthesized compounds were characterized by using various spectral techniques 1H NMR, 13C NMR, FT-IR, and mass spectroscopy methods. All newly synthesized compounds were evaluated in vitro for anticancer activity against the Human Breast Cancer Cell Line MDA-MB-231, and antioxidant activity was quantified using the DPPH free radical scavenging technique. The anticancer screening findings revealed that the synthesized compounds 3a, 3d, 3e, 3f, and 3j had GI50 of

Perfluoroalkyl substances (PFASs) are a category of high-concerned emerging contaminants which are suspected to correlate with various human adverse health outcomes including tumors. It is also a question whether short-chain PFASs are qualified alternatives under the regulation of long-chain PFASs. In this study, a three-dimensional (3D) culture system based on Gelatin methacrylate (GelMA) hydrogel matrix was used to investigate the impacts of 120-h perfluorooctanoic acid (PFOA) and perfluorobutanoic acid (PFBA) exposure of MDA-MB-231 cells. The results showed that PFOA exposure promoted the proliferation, migration, and invasion of MDA-MB-231 cells in an environmentally relevant concentration range (0.1 to 10 μM), exhibiting a clear malignant-promoting risk. In contrast, PFBA only showed a trend to induce non-invasive cell migration. Hippo/YAP signaling pathway was identified as the contributor to the differences between the two PFASs. PFOA but PFBA reduced YAP phosphorylation and increased the nuclear content of YAP, which further facilitated abundant key factors of epithelial-mesenchymal transition (EMT) process. Our results provided a new idea for the carcinogenicity of PFOA using a 3D-based paradigm. Although the effects by PFBA were much milder than PFOA in the current test duration, the cell model suitable for longer exposure is still necessary to better assess the safety of alternative short-chain PFASs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Photodynamic therapy (PDT) is a light-based anti-neoplastic therapeutic approach. Growing evidence indicates that combining conventional anti-cancer therapies with PDT can be a promising approach to treat malignancies. Herein, we aimed to investigate anti-cancer effects of the combination treatment of zinc phthalocyanine (ZnPc)-PDT with tamoxifen (TA) on MDA-MB-231 cells (as a triple-negative breast cancer (TNBC) cell line). For this purpose, we investigated the cytotoxicity of TA and ZnPc-PDT on MDA-MB-231 cells performing the MTT assay. The effect of TA and ZnPc-PDT on the apoptosis of MDA-MB-231 cells was studied using Annexin V/PI and DAPI staining. The wound-healing assay, and colony formation assay were performed to study the effect of TA and ZnPc-PDT on the migration, and clonogenicity of MDA-MB-231 cells, respectively. The qRT-PCR was done to study the gene expression of caspase-8, caspase-9, caspase-3, ZEB1, ROCK1, SNAIL1, CD133, CD44, SOX2, and ABCG2 (ATP-binding cassette sub-family G member 2). Based on our results, monotherapies with TA and ZnPc-PDT can remarkably increase cell cytotoxicity effects, stimulate apoptosis via downregulating Bcl-2 and upregulating caspase-3 and caspase-9, inhibit migration via downregulating SNAIL1 and ZEB1, and suppress clonogenicity via downregulating SOX2 and CD44 in MDA-MB-231 cells. Besides, these monotherapies can downregulate the expression of ABCG2 in MDA-MB-231 cells. Nevertheless, the combination treatment can potentiate the above-mentioned anti-cancer effects compared to monotherapy with TA. Of interest, the combined treatment of TA with ZnPc-PDT can synergically increase cell cytotoxicity effects on MDA-MB-231 cells. In fact, synergistic effects were estimated by calculation of Combination Index (CI); that synergistic outcomes were observed in all groups. Also, this combination treatment can significantly upregulate the caspase-8 gene expression and downregulate ROCK1 and CD133 gene expression in MDA-MB-231 cells. Overall, our results show that ZnPc-PDT can more sensitize the MDA-MB-231 cells to TA treatment. Based on our knowledge and experiment, the synergistic effects of ZnPc-PDT and TA deserve further evaluation in cancer research., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: The expression of p38 MAPK is high in breast cancer while its subunit p38γ had been rarely reported. We aimed to explain the effect of p38γ in breast cancer from the perspective of metabolomics., Methods: In this study, we detected the expression of p38γ in 28 breast carcinoma and para-tumor samples. Following MDA-MB-231 cell transfection with p38γ siRNAs and pc-DNA-3.1, cell viability, apoptosis, metastasis were determined through CCK-8, the cytometry analysis, transwell assay and wound healing assay. Finally, gas chromatograph-mass spectrometer (GC-MS) was used for analysis the differential metabolites., Results: The expression of p38γ was significantly up-regulated in breast cancer tissues. The transfection of si-p38γs could inhibit MDA-MB-231 cell propagation, metastasis, and induced cell apoptosis while overexpressed p38γ could promote the cell propagation, metastasis, and inhibit cell apoptosis. A total of 238 metabolites were identified and 72 of them differentially expressed in three groups (all P < 0.05, FDR < 0.05). Then the metabolites were enriched in the metabolism pathway, 85 pathways were included and 27 were significant (all P < 0.05, FDR < 0.05)., Conclusions: p38γ was up-regulated in breast cancer, which exerts a great influence on the cell growth, cell mobility, invasiveness, and apoptosis of MDA-MB-231 cells and also affected the metabolism., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Drug resistance in breast cancer remains a major obstacle of clinical therapy. We found that suppression of ELK3 in the triple negative breast cancer cell line MDA-MB-231 impaired autophagy and led to a hypersensitive response to doxorubicin treatment. In ELK3-knockdown MDA-MB-231 cells (ELK3 KD), autophagy was not activated under starvation conditions, which is a major stimulus of autophagy activation. We revealed that activation of the PI3K/Akt pathway was the main cause of impaired autophagy in ELK3 KD. Our results suggest that targeting ELK3 may be a potential approach to overcome doxorubicin resistance in breast cancer therapeutics., (Copyright © 2016. Published by Elsevier Inc.)