Enhanced Cytotoxicity of Doxorubicin by Micellar Photosensitizer-mediated Photochemical Internalization in Drug-resistant MCF-7 Cells

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.

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Implication of α5β1 integrin in invasion of drug-resistant MCF-7/ADR breast carcinoma cells: a role for MMP-2 collagenase

Biochemistry (Moscow) ◽

10.1134/s0006297908070079 ◽

2008 ◽

Vol 73 (7) ◽

pp. 791-796 ◽

Cited By ~ 10

Author(s):

G. E. Morozevich ◽

N. I. Kozlova ◽

I. B. Cheglakov ◽

N. A. Ushakova ◽

M. E. Preobrazhenskaya ◽

...

Keyword(s):

Breast Carcinoma ◽

Carcinoma Cells ◽

Drug Resistant ◽

Breast Carcinoma Cells ◽

Α5β1 Integrin ◽

Mcf 7

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Transfer of p14ARF gene in drug-resistant human breast cancer MCF-7/Adr cells inhibits proliferation and reduces doxorubicin resistance

Cancer Letters ◽

10.1016/s0304-3835(00)00524-3 ◽

2000 ◽

Vol 158 (2) ◽

pp. 203-210 ◽

Cited By ~ 6

Author(s):

F Guo-chang

Keyword(s):

Breast Cancer ◽

Human Breast Cancer ◽

Drug Resistant ◽

Human Breast ◽

Doxorubicin Resistance ◽

P14arf Gene ◽

Mcf 7

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APOBEC3B expression in drug resistant MCF-7 breast cancer cell lines

Biomedicine & Pharmacotherapy ◽

10.1016/j.biopha.2016.02.004 ◽

2016 ◽

Vol 79 ◽

pp. 87-92 ◽

Cited By ~ 1

Author(s):

Onder Onguru ◽

Serap Yalcin ◽

Cinthia Rosemblit ◽

Paul J. Zhang ◽

Selim Kilic ◽

...

Keyword(s):

Breast Cancer ◽

Cell Lines ◽

Cancer Cell ◽

Breast Cancer Cell ◽

Cancer Cell Lines ◽

Breast Cancer Cell Lines ◽

Drug Resistant ◽

Mcf 7

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ID: 1040 Anticancer effects of natural products from animal and plant origin

Biomedical Research and Therapy ◽

10.15419/bmrat.v4is.316 ◽

2017 ◽

Vol 4 (S) ◽

pp. 118

Author(s):

Goran Gajshi ◽

Josip Madunić ◽

Ivana Vrhovac Madunić ◽

Tamara Čimbora-Zovko ◽

Sanjica Rak ◽

...

Keyword(s):

Cell Death ◽

Western Blot ◽

Cell Lines ◽

Drug Resistant ◽

Plant Origin ◽

Anticancer Effect ◽

Different Types ◽

Dose Dependent ◽

Mcf 7

For last couple of decades, natural products have served us well in combating different types of cancer. The main sources of these useful compounds are from both animal and plant origin. Here we will present anticancer ability of bee venom (BV) and apigenin (API) towards different types of cancer cells in vitro. BV from honey bees is a complex mixture of a variety of different active peptides while API is a natural flavonoid found in several dietary plant foods. Anticancer effect of whole BV was tested in human cervical carcinoma HeLa cells and their drug-resistant HeLa CK subline while anticancer effect of API was tested in human breast cancer MCF-7 and MDA MB-231 cells. Cytotoxicity of both compounds towards cancer cells was evaluated by MTT assay whereas type of cell death was analysed by differential staining using acridine orange/ethidium bromide and was further verified by Western blot analysis. BV displayed dose-dependent cytotoxicity against both cell lines tested with drug-resistant HeLa CK cells being more sensitive to BV than their parental cell lines. Similarly, API inhibited the growth of both cell lines in a dose-dependent manner with MCF-7 cells being more sensitive. Treatment with BV induced a necrotic type of cell death, as shown by characteristic morphological features, fast staining with ethidium bromide and a lack of cleavage of apoptotic marker poly (ADP-ribose) polymerase (PARP) on Western blot. On the contrary, cell treated with API showed apoptosis as a dominant type of cell death in both cell lines which was further verified by Western blot analysis detecting cleaved PARP. In view of accumulating evidence on anti-proliferative and pro-cell death activity, both tested compounds could be used in the development of future anticancer drugs. Undoubtedly, therapeutic applications of BV and API are promising, however further in vitro and in vivo studies are warranted to resolve precise mechanisms responsible for their anticancer properties

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Effect of MiR-210 on the Chemosensitivity of Breast Cancer by Regulating JAK-STAT Signaling Pathway

BioMed Research International ◽

10.1155/2021/7703159 ◽

2021 ◽

Vol 2021 ◽

pp. 1-8

Author(s):

Zeyu Xing ◽

Xin Wang ◽

Jiaqi Liu ◽

Gang Liu ◽

Menglu Zhang ◽

...

Keyword(s):

Breast Cancer ◽

Signaling Pathway ◽

Western Blotting ◽

B Cell Lymphoma ◽

Expression Level ◽

Cell Counting ◽

Drug Resistant ◽

Stat Signaling ◽

Related Proteins ◽

Mcf 7

The study is aimed at exploring the effect of microribonucleic acid- (miR-) 210 on the chemosensitivity of breast cancer and its potential molecular mechanism. Cell Counting Kit-8 (CCK-8) was applied to detect the half maximal inhibitory concentration (IC50) of cisplatin (DDP) on cell, and quantitative polymerase chain reaction (qPCR) was carried out to measure the relative expression level of miR-210. The IC50 value of DDP on cells was detected via CCK-8 after downregulating the expression of miR-210 in MCF-7/DDP cells. Flow cytometry and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) confirmed the effect of themiR-210 downregulation on the apoptosis of drug-resistant MCF-7/DDP cells. Besides, the impacts of the miR-210 downregulation on apoptosis-related proteins and Janus-activated kinase- (JAK-) signal transducer and activator of transcription (STAT) signaling pathway-related proteins were examined by Western blotting. The interaction between miR-210 and the target protein was detected through luciferase activity assay, qPCR, and Western blotting. Drug-resistant MCF-7/DDP cells had significantly stronger resistance to DDP and a remarkably higher expression level of miR-210 than control parental MCF-7 cells ( p < 0.05 ). After the downregulation of the miR-210 expression, MCF-7/DDP cells had markedly reduced resistance but obviously increased sensitivity to DDP ( p < 0.05 ). MiR-210 downregulation increased the apoptosis of MCF-7/DDP cells ( p < 0.05 ). In addition, after miR-210 was knocked down, the expression level of b-cell lymphoma 2 (Bcl-2) was decreased, while the expression levels of Bcl-2-associated X protein (Bax) and cysteinyl aspartate-specific proteinase-3 (caspase-3) were increased. Besides, miR-210 was able to suppress the expression of protein inhibitor of the activated STAT 4 (PIAS4) gene by directly targeting its 3 ′ untranslated region (3 ′ UTR). The expression of miR-210 has a correlation with chemoresistance of breast cancer MCF-7 cells. MiR-210 regulates the JAK-STAT signal transduction pathway by targeting PIAS4, thus exerting an effect on breast cancer chemosensitivity.

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The In Vitro Anticancer Activity and Potential Mechanism of Action of 1-[(1R,2S)-2-fluorocyclopropyl]Ciprofloxacin-(4-methyl/phenyl/benzyl-3- aryl)-1,2,4-triazole-5(4H)-thione Hybrids

Current Topics in Medicinal Chemistry ◽

10.2174/1568026620666200310123723 ◽

2020 ◽

Vol 20 (16) ◽

pp. 1493-1498

Author(s):

Ya-Zhou Zhang ◽

Hai-Lin Liu ◽

Qian-Song He ◽

Zhi Xu

Keyword(s):

Breast Cancer ◽

Cell Lines ◽

Cancer Cell ◽

Anticancer Agents ◽

Topoisomerase Ii ◽

Cancer Cell Lines ◽

Breast Cancer Cell Lines ◽

Drug Resistant ◽

Mcf 7

Aims: Development of 1-[(1R, 2S)-2-fluorocyclopropyl]ciprofloxacin-1,2,4-triazole-5(4H)- thione hybrids as potential dual-acting mechanism anticancer agent to overcome the drug resistance. Background: Chemotherapy is an essential tool for the treatment of lung and female breast cancers, and numerous anticancer agents have been launched for this purpose. However, the clinical outcomes of chemotherapy are usually far from satisfactory due to the side effects and resistance to chemotherapeutic drugs. Thus, it is urgent to develop novel anti-lung and anti-breast cancer agents. Background: Chemotherapy is an essential tool for the treatment of lung and female breast cancers, and numerous anticancer agents have been launched for this purpose. However, the clinical outcomes of chemotherapy are usually far from satisfactory due to the side effects and resistance to chemotherapeutic drugs. Thus, it is urgent to develop novel anti-lung and anti-breast cancer agents. Objective: The primary objective of this study was to evaluate the potential of bis-isatin scaffolds with alkyl/ether linkers between the two isatin moieties against different human breast cancer cell lines including A549, MCF-7 and their drug-resistant counterparts A549/CDDP, MCF-7/ADM cells. Methods: The 1-[(1R, 2S)-2-fluorocyclopropyl]ciprofloxacin-(4-methyl/phenyl/benzyl-3-aryl)-1,2,4- triazole-5(4H)-thione hybrids were screened for their in vitro activity against drug-sensitive lung (A549), breast (MCF-7) and their drug-resistant counterparts A549/CDDP (cisplatin-resistant), MCF- 7/ADM (doxorubicin-resistant) cancer cell lines by MTT assay. The inhibitory activity of these hybrids against topoisomerase II and EGFR was also evaluated to investigate the potential mechanism of action of these hybrids. Result: The most prominent hybrid 7k (IC50: 37.28-49.05 µM) was comparable to Vorinostat against A549 and A549/CDDP lung cancer cells, and was 2.79-2.94 times more active than Vorinostat against MCF-7 and MCF-7/ADM breast cancer cell lines. Moreover, hybrid 7k (IC50: 8.6 and 16.4 µM) also demonstrated dual inhibition against topoisomerase II and EGFR. Conclusion: The 1-[(1R, 2S)-2-fluorocyclopropyl]ciprofloxacin-1,2,4-triazole-5(4H)-thione hybrids possess equally activity against both drug-sensitive cancer cells and their drug-resistant counterparts, and the majority of them were no inferior to the reference Vorinostat. The mechanistic study revealed that these hybrids could inhibit both topoisomerase II and EGFR, so these hybrids can be developed as dual-acting mechanism anticancer agents.

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Nano-Sized Micelles of Block Copolymers of Methoxy Poly(ethylene glycol)-Poly(ε-caprolactone)-Graft-2-Hydroxyethyl Cellulose for Doxorubicin Delivery

Journal of Nanoscience and Nanotechnology ◽

10.1166/jnn.2008.18275 ◽

2008 ◽

Vol 8 (5) ◽

pp. 2362-2368 ◽

Cited By ~ 4

Author(s):

Ming-Fa Hsieh ◽

Nguyen Van Cuong ◽

Chao-Hsuan Chen ◽

Yung Tsung Chen ◽

Jui-Ming Yeh

Keyword(s):

Block Copolymers ◽

Ethylene Glycol ◽

Water Soluble ◽

Hydroxyethyl Cellulose ◽

Drug Resistant ◽

Wild Type ◽

Poly Ethylene Glycol ◽

Poly Ethylene ◽

Mcf 7 ◽

Resistant Cells

The amphiphilic block copolymers methoxy poly(ethylene glycol)-poly(ε-caprolactone) was grafted to 2-hydroxyethyl cellulose to produce the water-soluble copolymers. Doxorubicin loaded nanoparticles were prepared by dialysis method and the sizes of nanoparticles were determined by dynamic light scattering in solution and atomic force microscopes. As results the sizes were detected in a range of 197.4 to 340.7 nm. The in-vitro release of Dox was studied in phosphate and acetate buffered solution at 37 °C. The results showed that 43 and 53% of Dox remained after an incubation period of 7 days. The cytotoxicity of Dox loaded micelles was investigated in two different human MCF-7/wild type and MCF-7/Adriamycin drug resistant cells lines. The Dox-loaded micelles showed reduced cytotoxicity compared to free Dox in MCF-7/wild type and MCF-7/Adriamycin drug resistant cells.

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