Nanomicelles Potentiate HDAC Inhibitor Efficacy In Vitro.

Abstract Background. Amphiphilic block copolymers used as nanomicelle drug carriers can effectively overcome poor drug solubility and specificity issues. Hence, these platforms have a broad applicability in cancer treatment. In this study, Pluronic F127 was used to fabricate nanomicelles containing the histone deacetylase inhibitor SAHA, which has an epigenetic-driven anti-cancer effect in several tumor types. SAHA loaded nanomicelles were prepared using a thin-film drying method and characterized for size, surface charge, drug content and drug release properties. Loaded particles were tested for in vitro activity and their effect on cell-cycle and markers of metastasis. Results. Following detailed particle characterization, cell proliferation experiments demonstrated that SAHA loaded nanomicelles more effectively inhibited the growth of HeLa and MCF-7 cell lines compared with free drug formulations. The 30nm SAHA containing nanoparticles were able to release up to 100% of the encapsulated drug over a 72h time window. Moreover, gene and protein expression analyses suggested that this effect was achieved through the regulation of p21 and p53 expression. SAHA was also shown to upregulate E-cadherin expression, potentially influencing tumor migration and metastasis.Conclusions. This study highlights the opportunity to exploit pluronic-based nanomicelles for the delivery of compounds that regulate epigenetic processes, thus inhibiting cancer development and progression.

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Nanomicelles potentiate histone deacetylase inhibitor efficacy in vitro.

10.21203/rs.3.rs-50247/v3 ◽

2020 ◽

Author(s):

Simone Pisano ◽

Xiong Wang ◽

Jezabel Garcia Parra ◽

Andrea Gazze ◽

Kadie Edwards ◽

...

Keyword(s):

Histone Deacetylase ◽

Cancer Progression ◽

Histone Deacetylase Inhibitor ◽

Time Window ◽

Drug Carriers ◽

Pluronic F127 ◽

P53 Expression ◽

Deacetylase Inhibitor ◽

Gene And Protein Expression

Abstract Background. Amphiphilic block copolymers used as nanomicelle drug carriers can effectively overcome poor drug solubility and specificity issues. Hence, these platforms have a broad applicability in cancer treatment. In this study, Pluronic F127 was used to fabricate nanomicelles containing the histone deacetylase inhibitor SAHA, which has an epigenetic-driven anti-cancer effect in several tumor types. SAHA loaded nanomicelles were prepared using a thin-film drying method and characterized for size, surface charge, drug content and drug release properties. Loaded particles were tested for in vitro activity and their effect on cell-cycle and markers of cancer progression. Results. Following detailed particle characterization, cell proliferation experiments demonstrated that SAHA loaded nanomicelles more effectively inhibited the growth of HeLa and MCF-7 cell lines compared with free drug formulations. The 30nm SAHA containing nanoparticles were able to release up to 100% of the encapsulated drug over a 72h time window. Moreover, gene and protein expression analyses suggested that their cytoreductive effect was achieved through the regulation of p21 and p53 expression. SAHA was also shown to upregulate E-cadherin expression, potentially influencing tumor migration. Conclusions. This study highlights the opportunity to exploit pluronic-based nanomicelles for the delivery of compounds that regulate epigenetic processes, thus inhibiting cancer development and progression.

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Nanomicelles potentiate histone deacetylase inhibitor efficacy in vitro

Cancer Nanotechnology ◽

10.1186/s12645-020-00070-8 ◽

2020 ◽

Vol 11 (1) ◽

Author(s):

S. Pisano ◽

X. Wang ◽

J. Garcia-Parra ◽

A. Gazze ◽

K. Edwards ◽

...

Keyword(s):

Histone Deacetylase ◽

Cancer Progression ◽

Histone Deacetylase Inhibitor ◽

Time Window ◽

Drug Carriers ◽

Pluronic F127 ◽

P53 Expression ◽

Deacetylase Inhibitor ◽

Gene And Protein Expression

Abstract Background Amphiphilic block copolymers used as nanomicelle drug carriers can effectively overcome poor drug solubility and specificity issues. Hence, these platforms have a broad applicability in cancer treatment. In this study, Pluronic F127 was used to fabricate nanomicelles containing the histone deacetylase inhibitor SAHA, which has an epigenetic-driven anti-cancer effect in several tumor types. SAHA-loaded nanomicelles were prepared using a thin-film drying method and characterized for size, surface charge, drug content, and drug release properties. Loaded particles were tested for in vitro activity and their effect on cell cycle and markers of cancer progression. Results Following detailed particle characterization, cell proliferation experiments demonstrated that SAHA-loaded nanomicelles more effectively inhibited the growth of HeLa and MCF-7 cell lines compared with free drug formulations. The 30 nm SAHA containing nanoparticles were able to release up to 100% of the encapsulated drug over a 72 h time window. Moreover, gene and protein expression analyses suggested that their cytoreductive effect was achieved through the regulation of p21 and p53 expression. SAHA was also shown to up-regulate E-cadherin expression, potentially influencing tumor migration. Conclusions This study highlights the opportunity to exploit pluronic-based nanomicelles for the delivery of compounds that regulate epigenetic processes, thus inhibiting cancer development and progression.

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Nanomicelles potentiate histone deacetylase inhibitor efficacy in vitro.

10.21203/rs.3.rs-50247/v2 ◽

2020 ◽

Author(s):

Simone Pisano ◽

Xiong Wang ◽

Jezabel Garcia Parra ◽

Andrea Gazze ◽

Kadie Edwards ◽

...

Keyword(s):

Histone Deacetylase ◽

Cancer Progression ◽

Histone Deacetylase Inhibitor ◽

Time Window ◽

Drug Carriers ◽

Pluronic F127 ◽

P53 Expression ◽

Deacetylase Inhibitor ◽

Gene And Protein Expression

Abstract Background. Amphiphilic block copolymers used as nanomicelle drug carriers can effectively overcome poor drug solubility and specificity issues. Hence, these platforms have a broad applicability in cancer treatment. In this study, Pluronic F127 was used to fabricate nanomicelles containing the histone deacetylase inhibitor SAHA, which has an epigenetic-driven anti-cancer effect in several tumor types. SAHA loaded nanomicelles were prepared using a thin-film drying method and characterized for size, surface charge, drug content and drug release properties. Loaded particles were tested for in vitro activity and their effect on cell-cycle and markers of cancer progression. Results. Following detailed particle characterization, cell proliferation experiments demonstrated that SAHA loaded nanomicelles more effectively inhibited the growth of HeLa and MCF-7 cell lines compared with free drug formulations. The 30nm SAHA containing nanoparticles were able to release up to 100% of the encapsulated drug over a 72h time window. Moreover, gene and protein expression analyses suggested that their cytoreductive effect was achieved through the regulation of p21 and p53 expression. SAHA was also shown to upregulate E-cadherin expression, potentially influencing tumor migration.Conclusions. This study highlights the opportunity to exploit pluronic-based nanomicelles for the delivery of compounds that regulate epigenetic processes, thus inhibiting cancer development and progression.

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Stereocomplexation Assisted Assembly of Poly(γ-glutamic Acid)-graft-polylactide Nano-micelles and Their Efficacy as Anticancer Drug Carrier

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520617666170911170104 ◽

2018 ◽

Vol 18 (2) ◽

pp. 302-311

Author(s):

Shulin Dai ◽

Yucheng Feng ◽

Shuyi Li ◽

Yuxiao Chen ◽

Meiqing Liu ◽

...

Keyword(s):

Glutamic Acid ◽

Drug Carrier ◽

Drug Loading ◽

Drug Carriers ◽

Cancer Drug ◽

Drug Release Profile ◽

Sustained Drug Release ◽

Anti Cancer ◽

Physical Interactions

Background: Micelles as drug carriers are characterized by their inherent instability due to the weak physical interactions that facilitate the self-assembly of amphiphilic block copolymers. As one of the strong physical interactions, the stereocomplexation between the equal molar of enantiomeric polylactides, i.e., the poly(L-lactide) (PLLA) and poly(D-lactide) (PDLA), may be harnessed to obtain micelles with enhanced stability and drug loading capacity and consequent sustained release. </P><P> Aims/Methods: In this paper, stereocomplexed micelles gama-PGA-g-PLA micelles) were fabricated from the stereocomplexation between poly(gama-glutamic acid)-graft-PLLA gama-PGA-g-PLA) and poly(gamaglutamic acid)-graft-PDLA gama-PGA-g-PLA). These stereocomplexed micelles exhibited a lower CMC than the corresponding enantiomeric micelles. Result: Furthermore, they showed higher drug loading content and drug loading efficiency in addition to more sustained drug release profile in vitro. In vivo imaging confirmed that the DiR-encapsulated stereocomplexed gama-PGA-g-PLA micelles can deliver anti-cancer drug to tumors with enhanced tissue penetration. Overall, gama-PGA-g-PLA micelles exhibited greater anti-cancer effects as compared with the free drug and the stereocomplexation may be a promising strategy for fabrication of anti-cancer drug carriers with significantly enhanced efficacy.

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In Vitro Anticancer Properties of Copper Metallodendrimers

Biomolecules ◽

10.3390/biom9040155 ◽

2019 ◽

Vol 9 (4) ◽

pp. 155 ◽

Cited By ~ 7

Author(s):

Hołota ◽

Magiera ◽

Michlewska ◽

Kubczak ◽

del Olmo ◽

...

Keyword(s):

Fluorescence Anisotropy ◽

Drug Carriers ◽

Haemolytic Activity ◽

Surface Groups ◽

Biological Processes ◽

Normal Cells ◽

Anticancer Properties ◽

Transmission Electron ◽

Anti Cancer

Newly synthesized carbosilane copper dendrimers (CCD) with chloride and nitrate surface groups seem to be good candidates to be used as gene and drug carriers in anti-cancer therapy, due to their properties such as size and surface charge. Copper attached to the nanoparticles is an important element of many biological processes and recently their anti-cancer properties have been widely examined. Zeta size and potential, transmission electron microscopy (TEM), circular dichroism (CD), analysis of haemolytic activity, and fluorescence anisotropy techniques were used to characterize copper dendrimers. Additionally, their cytotoxic properties toward normal (PBMC) and cancer (1301; HL-60) cells were examined. All tested dendrimers were more cytotoxic against cancer cells in comparison with normal cells.

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Expression of Wild-Type p53 by Curcumin, Alpinetin and Flavokawain B in Colorectal Cancer cells Expressing R273H Mutant p53

Nigerian Journal of Basic and Applied Sciences ◽

10.4314/njbas.v27i2.12 ◽

2020 ◽

Vol 27 (2) ◽

pp. 88-94

Author(s):

I. Malami ◽

A. Muhammad ◽

I.B. Abubakar ◽

A.M. Alhassan

Keyword(s):

Bioactive Compounds ◽

Mutant P53 ◽

Wild Type ◽

P53 Expression ◽

Gene And Protein Expression ◽

Colorectal Cancer Cells ◽

Binding Core ◽

Wild Type P53 ◽

Dose Dependent

A mutation in p53 is frequently reported in nearly 50% of all of human cancers arising from DNA-binding core domain of p53. DNA-contact mutant R273H rendered p53 at dysfunctional state due to the substitution of single residue Arg273 for His273. Here, natural bioactive compounds curcumin, alpinetin and flavokawain B were investigated for possible stabilisation of wild-type p53 expression in vitro using HT-29 cells harbouring R273H rendered p53. Accordingly, all the bioactive compounds were able to induce the expression of wild-type p53 both at the levels of gene and protein expression. A dose-dependent induction of p53 was evident at 12.5, 25 and 50 μM concentration. The present study has shown that the bioactive compounds may have restored the wild-type p53 functional activity in tumour cells expressing R273H mutant p53. Keywords: Curcumin, Alpinetin, Flavokawain B, p53, R273H

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Potential anti-cancer activity of N-hydroxy-7-(2-naphthylthio) heptanomide (HNHA), a histone deacetylase inhibitor, against breast cancer both in vitro and in vivo

Cancer Science ◽

10.1111/j.1349-7006.2010.01798.x ◽

2010 ◽

Vol 102 (2) ◽

pp. 343-350 ◽

Cited By ~ 9

Author(s):

Ki Cheong Park ◽

Seung Won Kim ◽

Ji Hyun Park ◽

Eun Hye Song ◽

Jeong Won Yang ◽

...

Keyword(s):

Breast Cancer ◽

Histone Deacetylase ◽

Histone Deacetylase Inhibitor ◽

Deacetylase Inhibitor ◽

Anti Cancer ◽

Cancer Activity

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A Gadolinium DO3A Amide m-Phenyl Boronic Acid MRI Probe for Targeted Imaging of Sialated Solid Tumors

Biomedicines ◽

10.3390/biomedicines9101459 ◽

2021 ◽

Vol 9 (10) ◽

pp. 1459

Author(s):

Christu Rajan ◽

Jaya Seema ◽

Yu-Wen Chen ◽

Tsai-Chen Chen ◽

Ming-Huang Lin ◽

...

Keyword(s):

Boronic Acid ◽

Time Window ◽

Tumor Diagnosis ◽

Targeted Imaging ◽

Phenyl Boronic Acid ◽

Cellular Labeling ◽

Tumor Accumulation ◽

Tumor Types

We developed a new probe, Gd-DO3A-Am-PBA, for imaging tumors. Our results showed active targeting of Gd-DO3A-Am-PBA to sialic acid (SA) moieties, with increased cellular labeling in vitro and enhanced tumor accumulation and retention in vivo, compared to the commercial Gadovist. The effectiveness of our newly synthesized probe lies in its adequate retention phase, which is expected to provide a suitable time window for tumor diagnosis and a faster renal clearance, which will reduce toxicity risks when translated to clinics. Hence, this study can be extended to other tumor types that express SA on their surface. Targeting and MR imaging of any type of tumors can also be achieved by conjugating the newly synthesized contrast agent with specific antibodies. This study thus opens new avenues for drug delivery and tumor diagnosis via imaging.

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Melatonin modifies tumor hypoxia and metabolism by inhibiting HIF-1α and energy metabolic pathway in the in vitro and in vivo models of breast cancer

Melatonin Research ◽

10.32794/mr11250042 ◽

2019 ◽

Vol 2 (4) ◽

pp. 83-98 ◽

Cited By ~ 2

Author(s):

André De Lima Mota ◽

Bruna Vitorasso Jardim-Perassi ◽

Tialfi Bergamin De Castro ◽

Jucimara Colombo ◽

Nathália Martins Sonehara ◽

...

Keyword(s):

Breast Cancer ◽

Glucose Metabolism ◽

Tumor Growth ◽

Tumor Cells ◽

Carbonic Anhydrases ◽

In Vivo Models ◽

Ca Ix ◽

Gene And Protein Expression

Breast cancer is the most common cancer among women and has a high mortality rate. Adverse conditions in the tumor microenvironment, such as hypoxia and acidosis, may exert selective pressure on the tumor, selecting subpopulations of tumor cells with advantages for survival in this environment. In this context, therapeutic agents that can modify these conditions, and consequently the intratumoral heterogeneity need to be explored. Melatonin, in addition to its physiological effects, exhibits important anti-tumor actions which may associate with modification of hypoxia and Warburg effect. In this study, we have evaluated the action of melatonin on tumor growth and tumor metabolism by different markers of hypoxia and glucose metabolism (HIF-1α, glucose transporters GLUT1 and GLUT3 and carbonic anhydrases CA-IX and CA-XII) in triple negative breast cancer model. In an in vitro study, gene and protein expressions of these markers were evaluated by quantitative real-time PCR and immunocytochemistry, respectively. The effects of melatonin were also tested in a MDA-MB-231 xenograft animal model. Results showed that melatonin treatment reduced the viability of MDA-MB-231 cells and tumor growth in Balb/c nude mice (p <0.05). The treatment significantly decreased HIF-1α gene and protein expression concomitantly with the expression of GLUT1, GLUT3, CA-IX and CA-XII (p <0.05). These results strongly suggest that melatonin down-regulates HIF-1α expression and regulates glucose metabolism in breast tumor cells, therefore, controlling hypoxia and tumor progression.

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