scholarly journals Uji Sitotoksitas dan Hambatan Ekspresi VEGF pada Sel 4T1 Minyak Atsiri Rimpang Curcuma mangga Val.

2021 ◽  
Vol 26 (2) ◽  
Author(s):  
Nurul Mukhlisa
Keyword(s):  
Triple Negative ◽  
Drug Resistant ◽  
Mcf 7

TNBC merupakan kanker payudara yang paling ganas dengan resiko kambuh dan metastasis yang tinggi. Terapi yang efektif untuk pasien TNBC adalah menggunakan kemoterapi, namun banyak pasien mengalami drug resistant yang dapat meningkatkan mortalitas. TNBC bersifat metastasis ke organ tubuh lain yang ditandai dengan terjadinya angiogenesis. VEGF merupakan salah satu factor angiogenik, sehingga studi hambatan ekspresi protein tersebut dapat digunakan sebagai target pengembangan obat anti TNBC. Rimpang Curcuma mangga Val. digunakan masyarakat Yogyakarta sebagai herbal antikanker payudara, dan minyak atsirinya bersifat sitotoksik terhadap sel kanker payudara T47D dan MCF-7; namun belum terbukti sitotoksik terhadap sel TNBC. Penelitian ini bertujuan untuk melihat potensi antikanker TNBC minyak atsiri rimpang C. mangga Val. melalui uji sitotoksisitasnya terhadap sel 4T1 dengan kontrol positif alpelisib, dan penghambatannya pada ekspresi protein VEGF. Hasil penelitian menunjukkan IC50 alpelisib terhadap sel kanker 4T1 adalah 32,975 µg/ml; sedangkan IC50 minyak atrisi C. mangga Val. adalah 91,96 µg/ml. Tidak ada perbedaan signifikan aktivitas penghambatan ekspresi protein VEGF antara minyak atsiri C. mangga Val dan alpelisib. Dapat disimpulkan bahwa minyak atsiri C. mangga Val. memiliki potensi antikanker payudara triple negative.

Influence of the calmodulin antagonist EBB on cyclin B1 and Cdc2-p34 in human drug-resistant breast cancer MCF-7/ADR cells

2008 ◽  
Vol 5 (2) ◽  
pp. 108-112 ◽  
Author(s):  
Xu Shi ◽  
Yanhong Cheng ◽  
Linglin Zou ◽  
Dongsheng Xiong ◽  
Yuan Zhou ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cyclin B1 ◽  
Drug Resistant ◽  
Calmodulin Antagonist ◽  
Mcf 7

Dihydrotestosterone induces chemo-resistance of triple-negative breast MDA-MB-231 cancer cells towards doxorubicin independent of ABCG2 and miR-328-3p

2021 ◽  
Vol 14 ◽  
Author(s):  
Bayan Al-Momany ◽  
Hana Hammad ◽  
Mamoun Ahram
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Drug Response ◽  
Therapeutic Strategy ◽  
Triple Negative ◽  
Model System ◽  
Cell Resistance ◽  
Protein Levels ◽  
Abcg2 Protein ◽  
Mcf 7

Background: Androgens potentially have an important role in the biology of breast cancer, particularly triple-negative breast cancer (TNBC). Androgen receptor (AR) may offer a novel therapeutic strategy including the use of microRNA (miRNA) molecules. We have previously shown that AR agonist, dihydrotestosterone (DHT), increases the expression of miR-328-3p in the TNBC MDA-MB-231 cells. One target of the latter miRNA is ATP-binding cassette subfamily G member 2 (ABCG2), which modulates the chemo-response of cancer cells by pumping out xenobiotics. Objective: Using MDA-MB-231 cells as a model system for TNBC, we hypothesized that DHT would induce cell sensitivity towards doxorubicin via increasing levels of miR-328-3p and, consequently, reducing ABCG2 levels. Methods: Chemo-response of cells towards doxorubicin, tamoxifen, and mitoxantrone was evaluated using cell viability MTT assay. Cells were transfected with both miR-328-3p mimic or antisense molecules. Real-time PCR was utilized to assess RNA levels and immunoblotting was performed to investigate levels of ABCG2 protein. PCR arrays were used to assess changes in the expression of drug response regulatory genes. Results: Contrary to our hypothesis, treating MDA-MB-231 cells with DHT, no effect towards tamoxifen or mitoxantrone and increased cell resistance towards doxorubicin were noted, concomitant with decreased expression of ABCG2. This under-expression of ABCG2 was also found in MCF-7 and MDA-MB-453 cells treated with DHT. Although miR-328-3p decreased ABCG2 mRNA and protein levels, the miRNA did not alter the chemo-response of cells towards doxorubicin and did not affect DHT-induced chemo-resistance. AR activation slightly decreased the expression of 5 genes, including insulin-like growth factor 1 receptor, that may explain the mechanism of DHT-induced chemo-resistance of cells. Conclusion: DHT regulates chemo-response via a mechanism independent of ABCG2 and miR-328-3p.

scholarly journals Fighting tubulin-targeting anticancer drug toxicity and resistance

2017 ◽  
Vol 24 (9) ◽  
pp. T107-T117 ◽  
Author(s):  
Roberta Visconti ◽  
Domenico Grieco
Keyword(s):  
Drug Toxicity ◽  
Kinase Activity ◽  
Triple Negative ◽  
Molecular Targets ◽  
Vinca Alkaloids ◽  
Drug Resistant ◽  
Castration Resistant Prostate Cancer ◽  
Mitotic Progression ◽  
Castration Resistant

Tubulin-targeting drugs, like taxanes and vinca alkaloids, are among the most effective anticancer therapeutics used in the clinic today. Specifically, anti-microtubule cancer drugs (AMCDs) have proven to be effective in the treatment of castration-resistant prostate cancer and triple-negative breast cancer. AMCDs, however, have limiting toxicities that include neutropenia and neurotoxicity, and, in addition, tumor cells can become resistant to the drugs after long-term use. Co-targeting mitotic progression/slippage with inhibition of the protein kinases WEE1 and MYT1 that regulate CDK1 kinase activity may improve AMCD efficacy, reducing the acquisition of resistance by the tumor and side effects from the drug and/or its vehicle. Other possible treatments that improve outcomes in the clinic for these two drug-resistant cancers, including new formulations of the AMCDs and pursuing different molecular targets, will be discussed.

scholarly journals Integrative analysis of mRNA and miRNA profiles identifies miR-193 and miR-210 as potential regulatory biomarkers in different molecular subtypes of breast cancer

2020 ◽  
Author(s):  
Adriane Feijo Evangelista ◽  
Renato J Oliveira ◽  
Viviane A O Silva ◽  
Rene A D C Vieira ◽  
Rui M Reis ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cell Line ◽  
Cell Lines ◽  
Breast Cancer Cell ◽  
Cancer Progression ◽  
Triple Negative ◽  
Molecular Subtypes ◽  
Breast Cancer Cell Lines ◽  
Mcf 7

Abstract Introduction: Breast cancer is the most frequently diagnosed malignancy among women. However, the role of microRNA expression in breast cancer progression is not fully understood. In this study we examined predictive interactions between differentially expressed miRNAs and mRNAs in breast cancer cell lines representative of the common molecular subtypes. Integrative bioinformatics analysis identified miR-193 and miR-210 as potential regulatory biomarkers of mRNA in breast cancer. Several recent studies have investigated these miRNAs in a broad range of tumors, but the mechanism of their involvement in cancer progression has not previously been investigated. Methods: The miRNA-mRNA interactions in breast cancer cell lines were identified by parallel expression analysis and miRNA target prediction programs. The expression profiles of mRNA and miRNAs from luminal (MCF-7, MCF-7/AZ and T47D), HER2 (BT20 and SK-BR3) and triple negative subtypes (Hs578T e MDA-MB-231) could be clearly separated by unsupervised analysis using HB4A cell line as a control. Breast cancer miRNA data from TCGA patients were grouped according to molecular subtypes and then used to validate these findings. Expression of miR-193 and miR-210 was investigated by miRNA transient silencing assays using the MCF7, BT20 and MDA-MB-231 cell lines. Functional studies included, xCELLigence system, ApoTox-Glo triplex, flow cytometry and transwell assays were performed to determine cell proliferation, cytotoxicity, apoptosis, migration and invasion, respectively. Results: The most evident effects were associated with cell proliferation after miR-210 silencing in triple negative subtype cell line MDA-MB-231. Using in silico prediction algorithms, TNFRSF10 was identified as one of the potential downstream targets for both miRNAs. The TNFRSF10C and TNFRSF10D mRNA expression inversely correlated with the expression levels of miR-193 and miR210 in breast cell lines and breast cancer patients, respectively. Other potential regulated genes whose expression also inversely correlated with both miRNAs were CCND1, a mediator on invasion and metastasis, and the tumor suppressor gene RUNX3. Conclusion: In summary, our findings identify miR-193 and miR-210 as potential regulatory miRNA in different molecular subtypes of breast cancer and suggest that miR-210 may have specific role in MDA-MB-231 proliferation. Our results highlight important new downstream regulated targets that may serve as promising therapeutic pathways for aggressive breast cancers.

scholarly journals Mitochondrial Targeting and pH-Responsive Nanogels for Co-Delivery of Lonidamine and Paclitaxel to Conquer Drug Resistance

2021 ◽  
Vol 9 ◽  
Author(s):  
Enping Chen ◽  
Ting Wang ◽  
Junmei Zhang ◽  
Xiang Zhou ◽  
Yafan Niu ◽  
...  
Keyword(s):  
Drug Loading ◽  
Ph Sensitive ◽  
Combination Regimen ◽  
Drug Efflux ◽  
Drug Resistant ◽  
Oxygen Species ◽  
Chemotherapeutic Drug ◽  
Mitochondrial Targeting ◽  
Ph Responsive ◽  
Mcf 7

Multidrug resistance (MDR) is one of the leading causes of the failure of cancer chemotherapy and mainly attributed to the overexpression of drug efflux transporters in cancer cells, which is dependent on adenosine triphosphate (ATP). To overcome this phenomenon, herein, a mitochondrial-directed pH-sensitive polyvinyl alcohol (PVA) nanogel incorporating the hexokinase inhibitor lonidamine (LND) and the chemotherapeutic drug paclitaxel (PTX) was developed to restore the activity of PTX and synergistically treat drug-resistant tumors. The introduction of 2-dimethylaminoethanethiol (DMA) moiety into the nanogels not only promoted the drug loading capacity but also enabled the lysosomal escape of the nanogels. The subsequent mitochondrial targeting facilitated the accumulation and acid-triggered payload release in the mitochondria. The released LND can destroy the mitochondria by exhausting the mitochondrial membrane potential (MMP), generating reactive oxygen species (ROS) and restraining the energy supply, resulting in apoptosis and susceptibility of the MCF-7/MDR cells to PTX. Hence, the nanogel-enabled combination regimen of LND and PTX showed a boosted anti-tumor efficacy in MCF-7/MDR cells. These mitochondrial-directed pH-sensitive PVA nanogels incorporating both PTX and LND represent a new nanoplatform for MDR reversal and enhanced therapeutic efficacy.

Design, synthesis, and anti-proliferative evaluation of 1H-1,2,3-triazole grafted tetrahydro-β-carboline-chalcone/ferrocenylchalcone conjugates in estrogen responsive and triple negative breast cancer cells

2020 ◽  
Vol 44 (26) ◽  
pp. 11137-11147 ◽  
Author(s):  
Bharvi Sharma ◽  
Liang Gu ◽  
Ruvesh Pascal Pillay ◽  
Nosipho Cele ◽  
Paul Awolade ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Triple Negative Breast Cancer ◽  
Breast Cancer Cells ◽  
Triple Negative ◽  
Design Synthesis ◽  
Mcf 7

A series of 1H-1,2,3 triazole grafted tetrahydro-β-carboline-chalcone/ferrocenylchalcone conjugates were synthesized and in vitro evaluated against estrogen responsive (MCF-7) and triple negative (MDA-MB-231) breast cancer cells.

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