Co-delivery of IL17RB siRNA and doxorubicin by chitosan-based nanoparticles for enhanced anticancer efficacy in breast cancer cells

2016 ◽  
Vol 83 ◽  
pp. 229-240 ◽  
Author(s):  
Vahideh Alinejad ◽  
Mohammad Hossein Somi ◽  
Behzad Baradaran ◽  
Parvin Akbarzadeh ◽  
Fatemeh Atyabi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Anticancer Efficacy

scholarly journals Repurposing of Fluvastatin as an Anticancer Agent against Breast Cancer Stem Cells via Encapsulation in a Hyaluronan-Conjugated Liposome

Pharmaceutics ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 1133
Author(s):  
Ji Yu ◽  
Dae Shin ◽  
Jin-Seok Kim
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Body Weight Loss ◽  
Breast Cancer Stem Cells ◽  
Anticancer Efficacy

Fluvastatin (FLUVA), which is a common anti-hypercholesterolemia drug, exhibits potential anticancer activity as it suppresses the proliferation, angiogenesis, and metastasis of breast cancer cells via inhibiting 3-hydroxy-methyl glutaryl-coenzyme A (HMG-CoA) reductase. In this study, hyaluronan-conjugated FLUVA-encapsulating liposomes (HA-L-FLUVA) were evaluated for their anticancer efficacy in vitro and in vivo. The particle size, zeta potential, and encapsulation efficiency of HA-L-FLUVA were 158.36 ± 1.78 nm, −24.85 ± 6.26 mV, and 35%, respectively. Growth inhibition of breast cancer stem cells (BCSCs) by HA-L-FLUVA was more effective than that by free FLUVA. The half maximal inhibitory concentration (IC50) values of FLUVA, L-FLVUA, and HA-L-FLUVA were 0.16, 0.17, and 0.09 μM, respectively. The in vivo anticancer effect of HA-L-FLUVA in combination with doxorubicin (DOX) was more effective than that of free FLUVA, free DOX, and HA-L-FLUVA. The longest survival of mice was achieved by treatment with FLUVA (15 mg/kg) and HA-L-FLUVA (15 mg/kg) + DOX (3 mg/kg), followed by HA-L-FLUVA (15 mg/kg), Dulbecco’s phosphate buffered saline, and DOX (3 mg/kg). No more than 10% body weight loss was observed in the mice injected with FLUVA, indicating that the drug was not toxic. Taken together, these results indicate that HA-L-FLUVA could serve as an effective anticancer drug by inhibiting the growth of both breast cancer cells and cancer stem cells.

scholarly journals NLRP3 as Putative Marker of Ipilimumab-Induced Cardiotoxicity in the Presence of Hyperglycemia in Estrogen-Responsive and Triple-Negative Breast Cancer Cells

2020 ◽  
Vol 21 (20) ◽  
pp. 7802 ◽  
Author(s):  
Vincenzo Quagliariello ◽  
Michelino De Laurentiis ◽  
Stefania Cocco ◽  
Giuseppina Rea ◽  
Annamaria Bonelli ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Triple Negative Breast Cancer ◽  
High Glucose ◽  
Breast Cancer Cells ◽  
Triple Negative ◽  
Anticancer Efficacy ◽  
Low Glucose ◽  
Mcf 7

Hyperglycemia, obesity and metabolic syndrome are negative prognostic factors in breast cancer patients. Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, achieving unprecedented efficacy in multiple malignancies. However, ICIs are associated with immune-related adverse events involving cardiotoxicity. We aimed to study if hyperglycemia could affect ipilimumab-induced anticancer efficacy and enhance its cardiotoxicity. Human cardiomyocytes and estrogen-responsive and triple-negative breast cancer cells (MCF-7 and MDA-MB-231 cell lines) were exposed to ipilimumab under high glucose (25 mM); low glucose (5.5 mM); high glucose and co-administration of SGLT-2 inhibitor (empagliflozin); shifting from high glucose to low glucose. Study of cell viability and the expression of new putative biomarkers of cardiotoxicity and resistance to ICIs (NLRP3, MyD88, cytokines) were quantified through ELISA (Cayman Chemical) methods. Hyperglycemia during treatment with ipilimumab increased cardiotoxicity and reduced mortality of breast cancer cells in a manner that is sensitive to NLRP3. Notably, treatment with ipilimumab and empagliflozin under high glucose or shifting from high glucose to low glucose reduced significantly the magnitude of the effects, increasing responsiveness to ipilimumab and reducing cardiotoxicity. To our knowledge, this is the first evidence that hyperglycemia exacerbates ipilimumab-induced cardiotoxicity and decreases its anticancer efficacy in MCF-7 and MDA-MB-231 cells. This study sets the stage for further tests on other breast cancer cell lines and primary cardiomyocytes and for preclinical trials in mice aimed to decrease glucose through nutritional interventions or administration of gliflozines during treatment with ipilimumab.

scholarly journals Anticancer Efficacy of Targeted Shikonin Liposomes Modified with RGD in Breast Cancer Cells

Molecules ◽  
2018 ◽  
Vol 23 (2) ◽  
pp. 268 ◽  
Author(s):  
Xianchun Wen ◽  
Jiping Li ◽  
Defu Cai ◽  
Liling Yue ◽  
Qi Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Anticancer Efficacy

Aloe-Emodin Enhances Tamoxifen Cytotoxicity by Suppressing Ras/ERK and PI3K/mTOR in Breast Cancer Cells

2017 ◽  
Vol 45 (02) ◽  
pp. 337-350 ◽  
Author(s):  
Hsin-Shun Tseng ◽  
Yu-Fen Wang ◽  
Yew-Min Tzeng ◽  
Dar-Ren Chen ◽  
Ya-Fan Liao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Aloe Vera ◽  
Breast Cancer Cell Lines ◽  
Anticancer Activities ◽  
Anticancer Efficacy ◽  
Aloe Emodin ◽  
Mcf 7

Aloe-emodin (AE) is derived from Aloe vera and rhubarb (Rheum palmatum) and exhibits anticancer activities via multiple regulatory mechanisms in various cancers. AE can also enhance the anticancer efficacy of cisplatin, doxorubicin, docetaxel, and 5-fluorouracil; however, its effects remain poorly characterized. MCF-7, MDA-MB-231, MDA-MB-468, BT-474, and HCC-1954 breast cancer cell lines were treated with the indicated conditions of AE, and cell viability assays were performed. The expression levels of signaling proteins were determined by western blot analysis, intracellular reactive oxygen species (ROS), cell cycle distributions, and rates of apoptosis as estimated by flow cytometry. In comparison with other cells, MCF-7 cells were more sensitive to AE treatment; AE enhanced the cytotoxicity of 9[Formula: see text][Formula: see text]g/ml tamoxifen by reducing EGFR, ER[Formula: see text], Ras, ERK, c-Myc, and mTOR protein expression and blocking PI3K and mTOR activation. Finally, although co-treatment of AE with tamoxifen increased intracellular ROS, there were no effects on cell cycle progression. Besides facilitating tamoxifen-induced cell death, AE also enhanced the antiproliferative activity of tamoxifen by blocking Ras/ERK and PI3K/mTOR pathways in breast cancer cells, thus demonstrating the chemosensitizing potential of AE.

Synergistic anti-breast cancer effect of pulsatilla saponin D and camptothecin through interrupting autophagic–lysosomal function and promoting p62-mediated ubiquitinated protein aggregation

2019 ◽  
Vol 41 (6) ◽  
pp. 804-816 ◽  
Author(s):  
Kai Wang ◽  
Yanbei Tu ◽  
Jian-Bo Wan ◽  
Meiwan Chen ◽  
Chengwei He
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Chemotherapeutic Agents ◽  
Mechanistic Study ◽  
Breast Cancer Cell Lines ◽  
Autophagic Flux ◽  
Anticancer Efficacy ◽  
Protein Levels ◽  
Novel Strategy

Abstract Autophagy is an evolutionarily conserved mechanism to protect the cells from unfavorable environmental conditions. Inhibition of autophagy has been contemplated as a novel strategy to enhance anticancer efficacy of existing chemotherapeutic agents. We previously reported that pulsatilla saponin D (PSD) was a potent autophagy inhibitor. However, its anticancer potential as adjuvant and underlying mechanisms are still unknown. In this study, we identified that PSD induced the formation of autophagosome in MCF-7 and MDA-MB-231 breast cancer cells. However, PSD alone and particularly co-treatment with camptothecin remarkably increased p62 protein levels, indicating that PSD strongly inhibited the autophagic cargo degradation. The mechanistic study indicated that PSD profoundly abolished the co-localization of EGFP-LC3 and lysosomal-specific probe LysoTracker Red, suggesting that the autophagosome–lysosome fusion was blocked by PSD, which is similar to the action of chloroquine. In addition, PSD significantly increased lysosomal pH and inhibited the activation of lysosomal cathepsins in both breast cancer cell lines. Furthermore, the accrued p62 resulted in accumulation of ubiquitinated proteins owing to the interaction with p62 and delivery to the malfunctioned autophagosome by PSD. Finally, we demonstrated that PSD synergistically enhanced the anticancer activity of camptothecin (CPT) in cultured breast cancer cells and in mouse xenograft tumor models. Our results indicated that PSD inhibited autophagic flux via blocking autophagosome–lysosome fusion and lysosomal acidification, which may confer a synergistic anti-breast cancer activity of PSD and CPT.

scholarly journals Eribulin and Paclitaxel Differentially Alter Extracellular Vesicles and Their Cargo from Triple-Negative Breast Cancer Cells

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2783
Author(s):  
Petra J. Pederson ◽  
Huiyun Liang ◽  
Daria Filonov ◽  
Susan L. Mooberry
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Extracellular Vesicles ◽  
Cancer Progression ◽  
Triple Negative Breast Cancer ◽  
Breast Cancer Cells ◽  
Triple Negative ◽  
Anticancer Efficacy ◽  
Mesenchymal Transition ◽  
Microtubule Targeting Agents

Extracellular vesicles play a central role in intercellular communication and contribute to cancer progression, including the epithelial-to-mesenchymal transition (EMT). Microtubule targeting agents (MTAs) including eribulin and paclitaxel continue to provide significant value in cancer therapy and their abilities to inhibit oncogenic signaling pathways, including eribulin’s capacity to reverse EMT are being revealed. Because microtubules are involved in the intracellular trafficking required for the formation and cargo loading of small extracellular vesicles (sEVs), we investigated whether MTA-mediated disruption of microtubule-dependent transport would impact sEV release and their cargo. Eribulin and paclitaxel caused an intracellular accumulation of CD63, a tetraspanin component of sEVs, in late/multivesicular endosomes of triple-negative breast cancer cells, consistent with the disruption of endosomal sorting and exosome cargo loading in these cells. While the concentrations of sEVs released from MTA-treated cells were not significantly altered, levels of CD63 and the CD63-associated cargos, ILK and β-integrin, were reduced in sEVs isolated from eribulin-treated HCC1937 cells as compared to vehicle or paclitaxel-treated cells. These results show that eribulin can reduce specific sEV cargos, including ILK, a major transducer of EMT in the tumor microenvironment, which may contribute to eribulin’s ability to reverse EMT to promote anticancer efficacy.

Co-delivery of doxorubicin and P-glycoprotein siRNA by multifunctional triblock copolymers for enhanced anticancer efficacy in breast cancer cells

2015 ◽  
Vol 3 (10) ◽  
pp. 2215-2228 ◽  
Author(s):  
Minghui Xu ◽  
Junmin Qian ◽  
Aili Suo ◽  
Ning Cui ◽  
Yu Yao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Triblock Copolymers ◽  
Triggered Release ◽  
Anticancer Efficacy ◽  
P Glycoprotein

The triblock copolymers can chemically conjugate DOX and simultaneously complex siRNA to form nanocomplexes exhibiting reduction- and pH-triggered release behaviors.

scholarly journals Ameliorated in vitro anticancer efficacy of methotrexate d-α-Tocopheryl polyethylene glycol 1000 succinate ester against breast cancer cells

2019 ◽  
Vol 5 (1) ◽  
Author(s):  
Arehalli S. Manjappa ◽  
Popat S. Kumbhar ◽  
Rohini Kasabe ◽  
Sonali K. Diwate ◽  
John I. Disouza
Keyword(s):  
Breast Cancer ◽  
Polyethylene Glycol ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Water Solubility ◽  
In Vivo Studies ◽  
Anticancer Efficacy ◽  
Study Results ◽  
Polyethylene Glycol 1000

Abstract Background Methotrexate (MTX), a folate anti-metabolite, has been used widely in the treatment of plenty of malignancies. However, the clinical use is limited because of its poor water solubility (BCS class II drug), nonspecific distribution, drug resistance, short circulation half-life, and toxicity. The objective of the present research was to synthesize the ester prodrug of MTX with d-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS) and characterize for in vitro anticancer efficacy. Results The FTIR and NMR results revealed the successful synthesis of the prodrug. The assay and saturation solubility of the prodrug is found to be 23 ± 2.5% and 6.7 ± 1.3 mg/mL (MTX equivalent) respectively. The CMC of the prodrug in distilled water at room temperature is found to be 36.9 ± 2.6 μg/mL. The prepared prodrug micelles showed a mean particle size of 166 ± 10 nm (PDI, 0.325 ± 0.09). Further, the TEM results confirmed the self-assembling character of the prodrug into micelles with a nearly spherical shape. The prodrug caused the significantly (p < 0.01) less hemolysis (16.8 ± 1.5%) when compared to plain MTX solution and significantly higher (p < 0.01) in vitro cytotoxicity, cell cycle arresting, and apoptosis against human breast cancer cells (MCF-7 and MDA-MB-231). Conclusion Our study results revealed the remarkable in vitro anticancer activity of MTX following its esterification with TPGS. However, further, in vivo studies are needed to prove its efficacy against different cancers.

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