Chitosan-Modified Silver Nanoparticles Enhance Cisplatin Activity in Breast Cancer Cells

Cancer therapy has been hindered by treatments lacking sensitivity, specificity, and affordability. The side effects of conventional chemotherapy enforce the need for a treatment strategy that would maximize the anti-cancer activity of the drug while minimizing its’ adverse effects on healthy cells. Nanoparticles (NPs) as carriers for anti-cancer drugs have attracted interest due to their favorable properties, which include the enhanced permeability and retention effect. Silver NPs (AgNPs) have been explored as nanocarriers owing to their good conductivity, chemical stability, and therapeutic potential. In this study, AgNPs were synthesized, functionalized with chitosan (CS), and loaded with the anti-cancer drug cisplatin (CIS). Successful conjugation, size distribution, and morphology of the NPs were assessed by UV-vis and Fourier transform infra-red (FTIR) spectroscopy, NP tracking analysis (NTA), and transmission electron microscopy (TEM). The encapsulated CIS (>80%) was efficiently and rapidly released from the nanocomplex at low pH, favoring delivery to a tumor micro-environment. Cytotoxicity profiles of the CS-AgNP-CIS nanocomplexes exhibited significant cell death in the human breast cancer cell lines, MCF-7 and SKBR-3. They were more effective than the free drug, exhibiting >50% cell death. Our results demonstrate a potentially efficient anti-cancer drug delivery system with selectivity to breast cancer cells.

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A radiosensitizer, gallotannin-rich extract from Bouea macrophylla seeds, inhibits radiation-induced epithelial-mesenchymal transition in breast cancer cells

BMC Complementary Medicine and Therapies ◽

10.1186/s12906-021-03363-6 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Jiraporn Kantapan ◽

Siwaphon Paksee ◽

Aphidet Duangya ◽

Padchanee Sangthong ◽

Sittiruk Roytrakul ◽

...

Keyword(s):

Breast Cancer ◽

Dna Damage ◽

Cell Death ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Epithelial Mesenchymal Transition ◽

Breast Cancer Cell Lines ◽

Mesenchymal Transition ◽

Mammosphere Formation ◽

Radiation Induced

Abstract Background Radioresistance can pose a significant obstacle to the effective treatment of breast cancers. Epithelial–mesenchymal transition (EMT) is a critical step in the acquisition of stem cell traits and radioresistance. Here, we investigated whether Maprang seed extract (MPSE), a gallotannin-rich extract of seed from Bouea macrophylla Griffith, could inhibit the radiation-induced EMT process and enhance the radiosensitivity of breast cancer cells. Methods Breast cancer cells were pre-treated with MPSE before irradiation (IR), the radiosensitizing activity of MPSE was assessed using the colony formation assay. Radiation-induced EMT and stemness phenotype were identified using breast cancer stem cells (CSCs) marker (CD24−/low/CD44+) and mammosphere formation assay. Cell motility was determined via the wound healing assay and transwell migration. Radiation-induced cell death was assessed via the apoptosis assay and SA-β-galactosidase staining for cellular senescence. CSCs- and EMT-related genes were confirmed by real-time PCR (qPCR) and Western blotting. Results Pre-treated with MPSE before irradiation could reduce the clonogenic activity and enhance radiosensitivity of breast cancer cell lines with sensitization enhancement ratios (SERs) of 2.33 and 1.35 for MCF7 and MDA-MB231cells, respectively. Pretreatment of breast cancer cells followed by IR resulted in an increased level of DNA damage maker (γ-H2A histone family member) and enhanced radiation-induced cell death. Irradiation induced EMT process, which displayed a significant EMT phenotype with a down-regulated epithelial marker E-cadherin and up-regulated mesenchymal marker vimentin in comparison with untreated breast cancer cells. Notably, we observed that pretreatment with MPSE attenuated the radiation-induced EMT process and decrease some stemness-like properties characterized by mammosphere formation and the CSC marker. Furthermore, pretreatment with MPSE attenuated the radiation-induced activation of the pro-survival pathway by decrease the expression of phosphorylation of ERK and AKT and sensitized breast cancer cells to radiation. Conclusion MPSE enhanced the radiosensitivity of breast cancer cells by enhancing IR-induced DNA damage and cell death, and attenuating the IR-induced EMT process and stemness phenotype via targeting survival pathways PI3K/AKT and MAPK in irradiated breast cancer cells. Our findings describe a novel strategy for increasing the efficacy of radiotherapy for breast cancer patients using a safer and low-cost natural product, MPSE.

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Data on the effects of anti-cancer drug of resveratrol in breast cancer cells, MDA-MB-231 cells

Data in Brief ◽

10.1016/j.dib.2017.03.029 ◽

2017 ◽

Vol 12 ◽

pp. 68-71 ◽

Cited By ~ 3

Author(s):

Eunmi Park

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Cancer Drug ◽

Anti Cancer

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Betulin Sulfonamides as Carbonic Anhydrase Inhibitors and Anticancer Agents in Breast Cancer Cells

International Journal of Molecular Sciences ◽

10.3390/ijms22168808 ◽

2021 ◽

Vol 22 (16) ◽

pp. 8808

Author(s):

Antje Güttler ◽

Yvonne Eiselt ◽

Anne Funtan ◽

Andreas Thiel ◽

Marina Petrenko ◽

...

Keyword(s):

Breast Cancer ◽

Cell Death ◽

Carbonic Anhydrase ◽

Cancer Cells ◽

Cancer Patients ◽

Breast Cancer Cells ◽

Clonogenic Survival ◽

Breast Cancer Cell Lines ◽

Protein Levels ◽

Ca Ix

Hypoxia-regulated protein carbonic anhydrase IX (CA IX) is up-regulated in different tumor entities and correlated with poor prognosis in breast cancer patients. Due to the radio- and chemotherapy resistance of solid hypoxic tumors, derivatives of betulinic acid (BA), a natural compound with anticancer properties, seem to be promising to benefit these cancer patients. We synthesized new betulin sulfonamides and determined their cytotoxicity in different breast cancer cell lines. Additionally, we investigated their effects on clonogenic survival, cell death, extracellular pH, HIF-1α, CA IX and CA XII protein levels and radiosensitivity. Our study revealed that cytotoxicity increased after treatment with the betulin sulfonamides compared to BA or their precursors, especially in triple-negative breast cancer (TNBC) cells. CA IX activity as well as CA IX and CA XII protein levels were reduced by the betulin sulfonamides. We observed elevated inhibitory efficiency against protumorigenic processes such as proliferation and clonogenic survival and the promotion of cell death and radiosensitivity compared to the precursor derivatives. In particular, TNBC cells showed benefit from the addition of sulfonamides onto BA and revealed that betulin sulfonamides are promising compounds to treat more aggressive breast cancers, or are at the same level against less aggressive breast cancer cells.

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Magnetic Alginate / Chitosan Nanoparticles for Targeted Delivery of Curcumin into Human Breast Cancer Cells

10.20944/preprints201809.0558.v1 ◽

2018 ◽

Author(s):

Wenxing Song ◽

Xing Su ◽

David Gregory ◽

Wei Li ◽

Zhiqiang Cai ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Therapy ◽

Cancer Cells ◽

Targeted Delivery ◽

Breast Cancer Cells ◽

Chitosan Nanoparticles ◽

Cancer Drug ◽

Uptake Efficiency ◽

Anti Cancer ◽

Hdf Cells

Curcumin is a promising anti-cancer drug but its applications in cancer therapy are limited due to its poor solubility, short half-life and low bioavailability. In this study, curcumin loaded magnetic alginate / chitosan nanoparticles were fabricated to improve the bioavailability, uptake efficiency and cytotoxicity of curcumin to MDA-MB-231 breast cancer cells. Alginate and chitosan were deposited on Fe3O4 magnetic nanoparticles based on their electrostatic properties. The sizes of the nanoparticles (120-200 nm) were within the optimum range for drug delivery. Sustained curcumin release was obtained use the nanoparticles with the ability to control the curcumin release rate by altering the number of chitosan and alginate layers. Confocal fluorescence microscopy results showed that targeted delivery of curcumin with the aid of magnetic field were achieved. The FACS assay indicated that MDA-MB-231 cells treated with curcumin loaded nanoparticles had a 3-6 folds uptake efficiency to those treated with free curcumin. MTT assay indicated that the curcumin loaded nanoparticles exhibited significantly higher cytotoxicity toward MDA-MB-231 cells than toward HDF cells. The sustained release profiles, enhanced uptake efficiency and cytotoxicity to cancer cells as well as the targeting potential make MACPs a promising candidate for cancer therapy.

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Impact of ethanolic extract of Mikania glomerata on human breast cancer (MCF 7) cell line

International Journal of Advances in Scientific Research ◽

10.7439/ijasr.v2i4.3259 ◽

2016 ◽

Vol 2 (4) ◽

pp. 94 ◽

Cited By ~ 1

Author(s):

Sarojini S. ◽

Senthilkumaar P. ◽

Ramesh V.

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Human Breast Cancer ◽

Breast Cancer Cells ◽

Ethanolic Extract ◽

Breast Cancer Cell Lines ◽

Human Breast ◽

Anti Cancer ◽

Mikania Glomerata ◽

Mcf 7

The ethanol extract of Mikania glomerata has anti-proliferative effect on the human breast cancer cell lines. The object of the present work is to investigate the anti-cancer effect of Mikania glomerata ethanolic extract on breast cancer. Soxlet fractions using crude ethanolic extract of Mikania glomerata was prepared by standard extraction protocols. To check the antiproliferative effect of this extract, the extract chosen was tested for cell viability on the breast cancer cells MCF 7 in different concentrations. Cell viability was evaluated by MTT assay for 24 hour and 48 hours. The LD50 value was calculated and different morphometric assays were performed with the effective dose of the extract. The effect of the extract on the normal cell was evaluated as well. Cell proliferation, cell cycle, Clonogenic survival, Apoptosis and MTT assays were performed. The ethanolic extract showed a dose-dependent and time dependent inhibition on cell proliferation in the breast cancer cell lines. It showed low cytotoxicity in the normal cells and inhibited cellular adhesion and wound healing in treated cancer cells. The present study suggests that the leaf extract from Mikania glomerata induces anticancer effect on the breast cancer cells. Further study might help to confirm it as an anti-cancer drug.

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Dovitinib Triggers Apoptosis and Autophagic Cell Death by Targeting SHP-1/p-STAT3 Signaling in Human Breast Cancers

Journal of Oncology ◽

10.1155/2019/2024648 ◽

2019 ◽

Vol 2019 ◽

pp. 1-14 ◽

Cited By ~ 2

Author(s):

Yi-Han Chiu ◽

Yi-Yen Lee ◽

Kuo-Chin Huang ◽

Cheng-Chi Liu ◽

Chen-Si Lin

Keyword(s):

Breast Cancer ◽

Cell Death ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Ectopic Expression ◽

Health Concern ◽

Breast Cancer Cell Lines ◽

Breast Cancers ◽

Human Breast ◽

Stat3 Inhibition

Breast cancer is the most common cancer and the leading cause of cancer deaths in women worldwide. The rising incidence rate and female mortality make it a significant public health concern in recent years. Dovitinib is a novel multitarget receptor tyrosine kinase inhibitor, which has been enrolled in several clinical trials in different cancers. However, its antitumor efficacy has not been well determined in breast cancers. Our results demonstrated that dovitinib showed significant antitumor activity in human breast cancer cell lines with dose- and time-dependent manners. Downregulation of phosphor-(p)-STAT3 and its subsequent effectors Mcl-1 and cyclin D1 was responsible for this drug effect. Ectopic expression of STAT3 rescued the breast cancer cells from cell apoptosis induced by dovitinib. Moreover, SHP-1 inhibitor reversed the downregulation of p-STAT3 induced by dovitinib, indicating that SHP-1 mediated the STAT3 inhibition effect of dovitinib. In addition to apoptosis, we found for the first time that dovitinib also activated autophagy to promote cell death in breast cancer cells. In conclusion, dovitinib induced both apoptosis and autophagy to block the growth of breast cancer cells by regulating the SHP-1-dependent STAT3 inhibition.

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Differential involvement of TAK1, RIPK1 and NF-κB signaling in Smac mimetic-induced cell death in breast cancer cells

Biological Chemistry ◽

10.1515/hsz-2018-0324 ◽

2019 ◽

Vol 400 (2) ◽

pp. 171-180 ◽

Cited By ~ 1

Author(s):

Nadine Schmidt ◽

Lisa Kowald ◽

Sjoerd J.L. van Wijk ◽

Simone Fulda

Keyword(s):

Breast Cancer ◽

T Cells ◽

Cell Death ◽

Cancer Cells ◽

Signaling Pathways ◽

Breast Cancer Cells ◽

Transforming Growth Factor ◽

Cancer Therapeutics ◽

Breast Cancer Cell Lines ◽

Smac Mimetics

Abstract Smac mimetics (SMs) are considered promising cancer therapeutics. However, the mechanisms responsible for mediating cell death by SMs are still only partly understood. Therefore, in this study, we investigated signaling pathways upon treatment with the bivalent SM BV6 using two SM-sensitive breast cancer cell lines as models. Interestingly, genetic silencing of transforming growth factor (TGF)β activated kinase (TAK)1, an upstream activator of the nuclear factor-kappaB (NF-κB) subunit RelA (p65), increased BV6-induced cell death only in EVSA-T cells, although it reduced BV6-mediated upregulation of tumor necrosis factor (TNF)α in both EVSA-T and MDA-MB-231 cells. By comparison, genetic silencing of p65, a key component of canonical NF-κB signaling, blocked BV6-induced cell death in MDA-MB-231 but not in EVSA-T cells. Similarly, knockdown of NF-κB-inducing kinase (NIK) rescued MDA-MB-231 cells from BV6-induced cell death, while it failed to do so in EVSA-T cells. Consistently, silencing of p65 or NIK reduced BV6-stimulated upregulation of TNFα in MDA-MB-231 cells. In conclusion, TAK1, receptor-interacting kinase 1 (RIPK1) as well as canonical and non-canonical NF-κB signaling are differentially involved in SM-induced cell death in breast cancer cells. These findings contribute to a better understanding of SM-induced signaling pathways.

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Anthocyanins Isolated from Vitis coignetiae Pulliat Enhances Cisplatin Sensitivity in MCF-7 Human Breast Cancer Cells through Inhibition of Akt and NF-κB Activation

Molecules ◽

10.3390/molecules25163623 ◽

2020 ◽

Vol 25 (16) ◽

pp. 3623 ◽

Cited By ~ 1

Author(s):

Anjugam Paramanantham ◽

Min Jeong Kim ◽

Eun Joo Jung ◽

Hye Jung Kim ◽

Seong-Hwan Chang ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Human Breast Cancer ◽

Breast Cancer Cells ◽

Breast Cancer Cell Lines ◽

Cell Phenotype ◽

Human Breast Cancer Cells ◽

Human Breast ◽

Anti Cancer ◽

Mcf 7

Anthocyanins isolated from Vitis coignetiae Pulliat (Meoru in Korea) (AIMs) have various anti-cancer properties by inhibiting Akt and NF-κB which are involved in drug resistance. Cisplatin (CDDP) is one of the popular anti-cancer agents. Studies reported that MCF-7 human breast cancer cells have high resistance to CDDP compared to other breast cancer cell lines. In this study, we confirmed CDDP resistance of MCF-7 cells and tested whether AIMs can overcome CDDP resistance of MCF-7 cells. Cell viability assay revealed that MCF-7 cells were more resistant to CDDP treatment than MDA-MB-231 breast cancer cells exhibiting aggressive and high cancer stem cell phenotype. AIMs significantly augmented the efficacy of CDDP with synergistic effects on MCF-7 cells. Molecularly, Western blot analysis revealed that CDDP strongly increased Akt and moderately reduced p-NF-κB and p-IκB and that AIMs inhibited CDDP-induced Akt activation, and augmented CDDP-induced reduction of p-NF-κB and p-IκB in MCF-7 cells. In addition, AIMs significantly downregulated an anti-apoptotic protein, XIAP, and augmented PARP-1 cleavage in CDDP-treated MCF-7 cells. Moreover, under TNF-α treatment, AIMs augmented CDDP efficacy with inhibition of NF-κB activation on MCF-7 cells. In conclusion, AIMs enhanced CDDP sensitivity by inhibiting Akt and NF-κB activity of MCF-7 cells that show relative intrinsic CDDP resistance.

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