scholarly journals Copper (II) Metallodendrimers Combined with Pro-Apoptotic siRNAs as a Promising Strategy Against Breast Cancer Cells

Pharmaceutics ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 727
Author(s):  
Natalia Sanz del Olmo ◽  
Marcin Holota ◽  
Sylwia Michlewska ◽  
Rafael Gómez ◽  
Paula Ortega ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Treatment ◽  
Anticancer Activity ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Viral Vectors ◽  
Viral Vector ◽  
Dendritic Structure ◽  
Carbosilane Dendrimers

Cancer treatment with small interfering RNA (siRNA) is one of the most promising new strategies; however, transfection systems that increase its bioavailability and ensure its delivery to the target cell are necessary. Transfection systems may be just vehicular or could contain fragments with anticancer activity that achieves a synergistic effect with siRNA. Cationic carbosilane dendrimers have proved to be powerful tools as non-viral vectors for siRNA in cancer treatment, and their activity might be potentiated by the inclusion of metallic complexes in its dendritic structure. We have herein explored the interaction between Schiff-base carbosilane copper (II) metallodendrimers, and pro-apoptotic siRNAs. The nanocomplexes formed by metallodendrimers and different siRNA have been examined for their zeta potential and size, and by transmission electron microscopy, fluorescence polarisation, circular dichroism, and electrophoresis. The internalisation of dendriplexes has been estimated by flow cytometry and confocal microscopy in a human breast cancer cell line (MCF-7), following the ability of these metallodendrimers to deliver the siRNA into the cell. Finally, in vitro cell viability experiments have indicated effective interactions between Cu (II) dendrimers and pro-apoptotic siRNAs: Mcl-1 and Bcl-2 in breast cancer cells. Combination of the first-generation derivatives with chloride counterions and with siRNA increases the anticancer activity of the dendriplex constructs and makes them a promising non-viral vector.

Botanical Therapeutics (Part II): Antimicrobial and In Vitro Anticancer Activity against MCF7 Human Breast Cancer Cells of Chamomile, Parsley and Celery Alcoholic Extracts

2020 ◽  
Vol 21 (2) ◽  
pp. 187-200
Author(s):  
Corina Danciu ◽  
Oana Cioanca ◽  
Claudia Watz Farcaș ◽  
Monica Hancianu ◽  
Roxana Racoviceanu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Anticancer Activity ◽  
Cancer Cells ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Human Breast Cancer Cells ◽  
Human Breast ◽  
Phytochemical Composition ◽  
Antimicrobial Potential

Background: This study was designed as a continuation of a complex investigation about the phytochemical composition and biological activity of chamomile, parsley, and celery extracts against A375 human melanoma and dendritic cells. Objective: The main aim was the evaluation of the antimicrobial potential of selected extracts as well as the in vitro anticancer activity against MCF7 human breast cancer cells. Methods: In order to complete the picture regarding the phytochemical composition, molecular fingerprint was sketched out by the help of FTIR spectroscopy. The activity of two enzymes (acetylcholinesterase and butyrylcholinesterase) after incubation with the three extracts was spectrophotometrically assessed. The antimicrobial potential was evaluated by disk diffusion method. The in vitro anticancer potential against MCF7 human breast cancer cells was appraised by MTT, LDH, wound healing, cell cycle, DAPI, Annexin-V-PI assays. Results: The results showed variations between the investigated extracts in terms of inhibitory activity against enzymes, such as acetyl- and butyrilcholinesterase. Chamomile and parsley extracts were active only against tested Gram-positive cocci, while all tested extracts displayed antifungal effects. Among the screened samples at the highest tested concentration, namely 60μg/mL, parsley was the most active extract in terms of reducing the viability of MCF7 - human breast adenocarcinoma cell line and inducing the release of lactate dehydrogenase. On the other hand, chamomile and celery extracts manifested potent anti-migratory effects. Furthermore, celery extract was the most active in terms of total apoptotic events, while chamomile extract induced the highest necrosis rate. Conclusion: The screened samples containing phytochemicals belonging in majority to the class of flavonoids and polyphenols can represent candidates for antimicrobial and anticancer agents.

scholarly journals Garcinol Regulates EMT and Wnt Signaling Pathways In Vitro and In Vivo, Leading to Anticancer Activity against Breast Cancer Cells

2012 ◽  
Vol 11 (10) ◽  
pp. 2193-2201 ◽  
Author(s):  
Aamir Ahmad ◽  
Sanila H. Sarkar ◽  
Bassam Bitar ◽  
Shadan Ali ◽  
Amro Aboukameel ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Wnt Signaling ◽  
Anticancer Activity ◽  
Cancer Cells ◽  
Signaling Pathways ◽  
Breast Cancer Cells

scholarly journals TBX15/miR-152/KIF2C Pathway Regulates Breast Cancer Doxorubicin Resistance via Preventing PKM2 Ubiquitination

2020 ◽  
Author(s):  
Cheng-Fei Jiang ◽  
Yun-Xia Xie ◽  
Ying-Chen Qian ◽  
Min Wang ◽  
Ling-Zhi Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Treatment ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Strategy Development ◽  
Luciferase Reporter ◽  
Doxorubicin Resistance ◽  
Novel Strategy ◽  
Cancer Tissues

Abstract BackgroundChemoresistance is a critical risk problem for breast cancer treatment. However, mechanisms by which chemoresistance arises remains to be elucidated. The expression of T-box transcription factor 15 (TBX-15) was found downregulated in some cancer tissues. However, role and mechanism of TBX15 in breast cancer chemoresistance is unknown. Here we aimed to identify the effects and mechanisms of TBX15 in doxorubicin resistance in breast cancer.MethodsAs measures of Drug sensitivity analysis, MTT and IC50 assays were used in DOX-resistant breast cancer cells. ECAR and OCR assays were used to analyze the glycolysis level, while Immunoblotting and Immunofluorescence assays were used to analyze the autophagy levels in vitro. By using online prediction software, luciferase reporter assays, co-Immunoprecipitation, Western blotting analysis and experimental animals models, we further elucidated the mechanisms.ResultsWe found TBX15 expression levels were decreased in Doxorubicin (DOX)-resistant breast cancer cells. Overexpression of TBX15 reversed the DOX resistance by inducing microRNA-152 (miR-152) expression. We found that KIF2C levels were highly expressed in DOX-resistant breast cancer tissues and cells, and KIF2C was a potential target of miR-152. TBX15 and miR-152 overexpression suppressed autophagy and glycolysis in breast cancer cells, while KIF2C overexpression reversed the process. Overexpression of KIF2C increased DOX resistance in cancer cells. Furthermore, KIF2C directly binds with PKM2 for inducing the DOX resistance. KIF2C can prevent the ubiquitination of PKM2 and increase its protein stability. In addition, we further identified that Domain-2 of KIF2C played a major role in the binding with PKM2 and preventing PKM2 ubiquitination, which enhanced DOX resistance by promoting autophagy and glycolysis. ConclusionsOur data identify a new mechanism by which TBX15 abolishes DOX chemoresistance in breast cancer, and suggest that TBX15/miR-152/KIF2C axis is a novel signaling pathway for mediating DOX resistance in breast cancer through regulating PKM2 ubiquitination and the enhancement of PKM2 stability. This finding suggests new therapeutic target and/or novel strategy development for cancer treatment to overcome drug resistance in the future.

scholarly journals Anticancer Activity of N-Hexane Extract from Sphagneticola trilobata (L.) J.F Pruski Against MCF-7 Breast Cancer Cell

Elkawnie ◽  
2020 ◽  
Vol 6 (1) ◽  
pp. 48 ◽  
Author(s):  
Vivi Mardina ◽  
Tisna Harmawan ◽  
Halimatussakdiah Halimatussakdiah ◽  
Syafruddin Ilyas ◽  
Masitta Tanjung
Keyword(s):  
Breast Cancer ◽  
Anticancer Activity ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Probit Analysis ◽  
Hexane Extract ◽  
Tetrazolium Salt ◽  
Cytotoxicity Test ◽  
Mcf 7

Abstract : Sphagneticola trilobata (L.) J.F. Pruski is one of the perennial herbs that is widely used by the national and international community to treat various diseases including cancer. The objective of this study was to assessment the anticancer activity of n-hexane extract of S. trilobata leaves for inhibiting the growth of MCF-7 breast cancer cells in vitro by MTT (microculture tetrazolium salt) method. The n-hexane extract of sernai leaves was obtained from the maceration process of samples that were collected from the Langsa city, Aceh. The cytotoxicity test was carried out by incubating MCF-7 cells which had been exposed to several series of sample levels, viz. 1000; 500; 100; 50; 25; 10; 5 and 1 µg/mL. LC50 values are calculated using probit analysis. The results revealed that the n-hexane extract of S. trilobata leaves was cytotoxic against breast cancer cells (MCF-7) with an LC50 value of  0.037 μg /mL.Abstrak : Sphagneticola trilobata (L.) J.F. Pruski merupakan salah satu tanaman herbal yang digunakan secara luas oleh masyarakat nasional dan internasional untuk mengobati berbagai penyakit termasuk kanker. Penelitian ini bertujuan untuk mengetahui aktivitas antikanker ekstrak n-heksana daun S. trilobata dalam menghambat pertumbuhan sel kanker payudara MCF-7 secara in vitro dengan metode MTT (microculture tetrazolium salt). Ekstrak n-heksana daun sernai diperoleh dari proses maserasi sampel yang dikoleksi dari kota Langsa, Aceh. Uji sitotoksisitas dilakukan dengan menginkubasi sel MCF-7 yang telah dipaparkan beberapa seri  kadar sampel yaitu 1000, 500, 100, 50, 25, 10, 5 dan 1 µg/mL. Nilai LC50 dihitung dengan menggunakan analisa probit. Hasil penelitian menunjukkan bahwa ekstrak n-heksana daun S. trilobata bersifat sitotoksik terhadap sel kanker payudara (MCF-7) dengan harga LC50 sebesar 0,037 µg/mL. 

scholarly journals Evaluation of β-Sitosterol Loaded PLGA and PEG-PLA Nanoparticles for Effective Treatment of Breast Cancer: Preparation, Physicochemical Characterization, and Antitumor Activity

Pharmaceutics ◽  
2018 ◽  
Vol 10 (4) ◽  
pp. 232 ◽  
Author(s):  
Moses Andima ◽  
Gabriella Costabile ◽  
Lorenz Isert ◽  
Albert Ndakala ◽  
Solomon Derese ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Flow Cytometry ◽  
Anticancer Activity ◽  
Cancer Cells ◽  
Size Distribution ◽  
Antiproliferative Activity ◽  
Breast Cancer Cells ◽  
Encapsulation Efficiency ◽  
Plga Nanoparticles

β-Sitosterol (β-Sit) is a dietary phytosterol with demonstrated anticancer activity against a panel of cancers, but its poor solubility in water limits its bioavailability and therapeutic efficacy. In this study, poly(lactide-co-glycolic acid) (PLGA) and block copolymers of poly(ethylene glycol)-block-poly(lactic acid) (PEG-PLA) were used to encapsulate β-Sit into nanoparticles with the aim of enhancing its in vitro anticancer activity. β-Sitosterol-loaded PLGA and PEG-PLA nanoparticles (β-Sit-PLGA and β-Sit-PEG-PLA) were prepared by using a simple emulsion-solvent evaporation technique. The nanoparticles were characterized for size, particle size distribution, surface charge, and encapsulation efficiency. Their cellular uptake and antiproliferative activity was evaluated against MCF-7 and MDA-MB-231 human breast cancer cells using flow cytometry and MTT assays, respectively. β-Sit-PLGA and β-Sit-PEG-PLA nanoparticles were spherical in shape with average particle sizes of 215.0 ± 29.7 and 240.6 ± 23.3 nm, a zeta potential of −13.8 ± 1.61 and −23.5 ± 0.27 mV, respectively, and with narrow size distribution. The encapsulation efficiency of β-Sit was 62.89 ± 4.66 and 51.83 ± 19.72 % in PLGA and PEG-PLA nanoparticles, respectively. In vitro release in phosphate-buffered saline (PBS) and PBS/with 0.2% Tween 20 showed an initial burst release, followed by a sustained release for 408 h. β-Sit-PLGA nanoparticles were generally stable in a protein-rich medium, whereas β-Sit-PEG-PLA nanoparticles showed a tendency to aggregate. Flow cytometry analysis (FACS) indicated that β-Sit-PLGA nanoparticles were efficiently taken up by the cells in contrast to β-Sit-PEG-PLA nanoparticles. β-Sit-PLGA nanoparticles were therefore selected to evaluate antiproliferative activity. Cell viability was inhibited by up to 80% in a concentration range of 6.64–53.08 μg/mL compared to the untreated cells. Taken together, encapsulation of β-Sitosterol in PLGA nanoparticles is a promising strategy to enhance its anticancer activity against breast cancer cells.

scholarly journals TBX15/miR-152/KIF2C Pathway Regulates Breast Cancer Doxorubicin Resistance Via Promoting PKM2 Ubiquitination

2021 ◽  
Author(s):  
Cheng-Fei Jiang ◽  
Yun-Xia Xie ◽  
Ying-Chen Qian ◽  
Min Wang ◽  
Ling-Zhi Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Treatment ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Strategy Development ◽  
Luciferase Reporter ◽  
Doxorubicin Resistance ◽  
Novel Strategy ◽  
Cancer Tissues

Abstract Background: Chemoresistance is a critical risk problem for breast cancer treatment. However, mechanisms by which chemoresistance arises remains to be elucidated. The expression of T-box transcription factor 15 (TBX-15) was found downregulated in some cancer tissues. However, role and mechanism of TBX15 in breast cancer chemoresistance is unknown. Here we aimed to identify the effects and mechanisms of TBX15 in doxorubicin resistance in breast cancer.Methods: As measures of Drug sensitivity analysis, MTT and IC50 assays were used in DOX-resistant breast cancer cells. ECAR and OCR assays were used to analyze the glycolysis level, while Immunoblotting and Immunofluorescence assays were used to analyze the autophagy levels in vitro. By using online prediction software, luciferase reporter assays, co-Immunoprecipitation, Western blotting analysis and experimental animals models, we further elucidated the mechanisms.Results: We found TBX15 expression levels were decreased in Doxorubicin (DOX)-resistant breast cancer cells. Overexpression of TBX15 reversed the DOX resistance by inducing microRNA-152 (miR-152) expression. We found that KIF2C levels were highly expressed in DOX-resistant breast cancer tissues and cells, and KIF2C was a potential target of miR-152. TBX15 and miR-152 overexpression suppressed autophagy and glycolysis in breast cancer cells, while KIF2C overexpression reversed the process. Overexpression of KIF2C increased DOX resistance in cancer cells. Furthermore, KIF2C directly binds with PKM2 for inducing the DOX resistance. KIF2C can prevent the ubiquitination of PKM2 and increase its protein stability. In addition, we further identified that Domain-2 of KIF2C played a major role in the binding with PKM2 and preventing PKM2 ubiquitination, which enhanced DOX resistance by promoting autophagy and glycolysis. Conclusions: Our data identify a new mechanism by which TBX15 abolishes DOX chemoresistance in breast cancer, and suggest that TBX15/miR-152/KIF2C axis is a novel signaling pathway for mediating DOX resistance in breast cancer through regulating PKM2 ubiquitination and decreasing PKM2 stability. This finding suggests new therapeutic target and/or novel strategy development for cancer treatment to overcome drug resistance in the future.

scholarly journals Antiestrogenic Activity of the Xi-Huang Formula for Breast Cancer by Targeting the Estrogen Receptor α

2018 ◽  
Vol 47 (6) ◽  
pp. 2199-2215 ◽  
Author(s):  
Jian Hao ◽  
Ziqi Jin ◽  
Hongxu Zhu ◽  
Xiaohui Liu ◽  
Yu Mao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Molecular Docking ◽  
Systems Biology ◽  
Cancer Treatment ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Breast Cancer Treatment

Background/Aims: The Xi-Huang (XH) formula has been used for breast cancer treatment in traditional Chinese medicine (TCM) since 1740. In this study, we show that, XH extract could suppress the growth of breast cancer cells in vitro and in vivo, and that it preferentially inhibits cell growth of estrogen receptor positive (ER+) breast cancer cells. Presently, little is known about the potential mechanism of XH and our studies aim to elucidate its mechanism in breast cancer treatment. Methods: Network-based systems biology and molecular docking analyses were performed to predict explicit targets of XH and active ingredients in XH. The effects of XH on cell viability, cell cycle, apoptosis in different breast cancer cell lines were analyzed in vitro. A model of transplanted tumors on nude mice was used to study the anticancer effect in vivo. Various techniques, including western blotting, reverse transcription-polymerase chain reaction (RT-PCR), immunofluorescence, co-immunoprecipitation and immunohistochemical were utilized to assess the expression of targets of XH in vitro and in vivo. RNA sequencing (RNA-seq) was performed to study the gene targets of XH. Furthermore, we analyzed of protein-ligand binding reactions by isothermal titration calorimetry (ITC). Results: Using network-based systems biology and molecular docking analyses, we predicted that the major targets of XH were ERα and HSP90. Moreover, we found that, XH mediated its anti-cancer effects by promoting the disassociation of ERα and HSP90, resulting in the degradation of ERα and blockade of transport of ERα to the nucleus. XH also caused the dissociation of ERα and other oncoproteins via binding to HSP90. Some of the active ingredients in XH share a common cyclopentane hydrogen skeleton and were predicted to target ERα based on the structural similarity. Conclusions: XH, which has been used since 1740, has antiestrogenic effects in breast cancer via the targeting of ERα.

scholarly journals TBX15/miR-152/KIF2C pathway regulates breast cancer doxorubicin resistance via promoting PKM2 ubiquitination

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Cheng-Fei Jiang ◽  
Yun-Xia Xie ◽  
Ying-Chen Qian ◽  
Min Wang ◽  
Ling-Zhi Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Treatment ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Strategy Development ◽  
Luciferase Reporter ◽  
Doxorubicin Resistance ◽  
Novel Strategy ◽  
Cancer Tissues

Abstract Background Chemoresistance is a critical risk problem for breast cancer treatment. However, mechanisms by which chemoresistance arises remains to be elucidated. The expression of T-box transcription factor 15 (TBX-15) was found downregulated in some cancer tissues. However, role and mechanism of TBX15 in breast cancer chemoresistance is unknown. Here we aimed to identify the effects and mechanisms of TBX15 in doxorubicin resistance in breast cancer. Methods As measures of Drug sensitivity analysis, MTT and IC50 assays were used in DOX-resistant breast cancer cells. ECAR and OCR assays were used to analyze the glycolysis level, while Immunoblotting and Immunofluorescence assays were used to analyze the autophagy levels in vitro. By using online prediction software, luciferase reporter assays, co-Immunoprecipitation, Western blotting analysis and experimental animals models, we further elucidated the mechanisms. Results We found TBX15 expression levels were decreased in Doxorubicin (DOX)-resistant breast cancer cells. Overexpression of TBX15 reversed the DOX resistance by inducing microRNA-152 (miR-152) expression. We found that KIF2C levels were highly expressed in DOX-resistant breast cancer tissues and cells, and KIF2C was a potential target of miR-152. TBX15 and miR-152 overexpression suppressed autophagy and glycolysis in breast cancer cells, while KIF2C overexpression reversed the process. Overexpression of KIF2C increased DOX resistance in cancer cells. Furthermore, KIF2C directly binds with PKM2 for inducing the DOX resistance. KIF2C can prevent the ubiquitination of PKM2 and increase its protein stability. In addition, we further identified that Domain-2 of KIF2C played a major role in the binding with PKM2 and preventing PKM2 ubiquitination, which enhanced DOX resistance by promoting autophagy and glycolysis. Conclusions Our data identify a new mechanism by which TBX15 abolishes DOX chemoresistance in breast cancer, and suggest that TBX15/miR-152/KIF2C axis is a novel signaling pathway for mediating DOX resistance in breast cancer through regulating PKM2 ubiquitination and decreasing PKM2 stability. This finding suggests new therapeutic target and/or novel strategy development for cancer treatment to overcome drug resistance in the future.

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