Fucoidan-Based Nanoparticles with Inherently Therapeutic Efficacy for Cancer Treatment

The anticancer properties of fucoidan have been widely studied in cancer research. However, the lack of safety information on the parenteral administration of fucoidan and its rapid clearance from the system have limited its application. Herein, we assessed the therapeutic efficacy and safety of fucoidan and developed fucoidan nanoparticles (FuNPs) to enhance their therapeutic effect in the mouse model of breast cancer. FuNPs were synthesized through the emulsion method, and the stable colloid has an average size of 216.3 nm. FuNPs were efficiently internalized into breast cancer cells in vitro, demonstrating an enhanced antitumor activity in comparison with free form fucoidan. After the treatment of FuNPs, the tumor progression was significantly inhibited in viv. The tumor volume was reduced by 2.49-fold compared with the control group. Moreover, the inhibition of the invasion of tumor cells into the lungs revealed the antimetastatic properties of the FuNPs. FuNPs, as naturally marine polysaccharide-based nanoparticles, have shown their broader therapeutic window and enhanced antimetastatic ability, opening an avenue to the development of the inherently therapeutic nanomedicines.

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A Novel Triazole Derivative Drug Presenting In Vitro and In Vivo Anticancer Properties

Current Topics in Medicinal Chemistry ◽

10.2174/1568026618666180917100640 ◽

2018 ◽

Vol 18 (17) ◽

pp. 1483-1493

Author(s):

Ricardo Imbroisi Filho ◽

Daniel T.G. Gonzaga ◽

Thainá M. Demaria ◽

João G.B. Leandro ◽

Dora C.S. Costa ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Cell Line ◽

Cancer Cell ◽

Cancer Cell Line ◽

Hepatic Function ◽

Anticancer Properties ◽

Mcf 7

Background: Cancer is a major cause of death worldwide, despite many different drugs available to treat the disease. This high mortality rate is largely due to the complexity of the disease, which results from several genetic and epigenetic changes. Therefore, researchers are constantly searching for novel drugs that can target different and multiple aspects of cancer. Experimental: After a screening, we selected one novel molecule, out of ninety-four triazole derivatives, that strongly affects the viability and proliferation of the human breast cancer cell line MCF-7, with minimal effects on non-cancer cells. The drug, named DAN94, induced a dose-dependent decrease in MCF-7 cells viability, with an IC50 of 3.2 ± 0.2 µM. Additionally, DAN94 interfered with mitochondria metabolism promoting reactive oxygen species production, triggering apoptosis and arresting the cancer cells on G1/G0 phase of cell cycle, inhibiting cell proliferation. These effects are not observed when the drug was tested in the non-cancer cell line MCF10A. Using a mouse model with xenograft tumor implants, the drug preventing tumor growth presented no toxicity for the animal and without altering biochemical markers of hepatic function. Results and Conclusion: The novel drug DAN94 is selective for cancer cells, targeting the mitochondrial metabolism, which culminates in the cancer cell death. In the end, DAN94 has been shown to be a promising drug for controlling breast cancer with minimal undesirable effects.

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Formulation of Piperine–Chitosan-Coated Liposomes: Characterization and In Vitro Cytotoxic Evaluation

Molecules ◽

10.3390/molecules26113281 ◽

2021 ◽

Vol 26 (11) ◽

pp. 3281

Author(s):

Syed Sarim Imam ◽

Sultan Alshehri ◽

Mohammad A. Altamimi ◽

Afzal Hussain ◽

Wajhul Qamar ◽

...

Keyword(s):

Breast Cancer ◽

Cell Line ◽

Cancer Cell ◽

Breast Cancer Cell ◽

Breast Cancer Cell Line ◽

Therapeutic Efficacy ◽

Cancer Cell Line ◽

Permeation Study ◽

Study Results

The present research work is designed to prepare and evaluate piperine liposomes and piperine–chitosan-coated liposomes for oral delivery. Piperine (PPN) is a water-insoluble bioactive compound used for different diseases. The prepared formulations were evaluated for physicochemical study, mucoadhesive study, permeation study and in vitro cytotoxic study using the MCF7 breast cancer cell line. Piperine-loaded liposomes (PLF) were prepared by the thin-film evaporation method. The selected liposomes were coated with chitosan (PLFC) by electrostatic deposition to enhance the mucoadhesive property and in vitro therapeutic efficacy. Based on the findings of the study, the prepared PPN liposomes (PLF3) and chitosan coated PPN liposomes (PLF3C1) showed a nanometric size range of 165.7 ± 7.4 to 243.4 ± 7.5, a narrow polydispersity index (>0.3) and zeta potential (−7.1 to 29.8 mV). The average encapsulation efficiency was found to be between 60 and 80% for all prepared formulations. The drug release and permeation study profile showed biphasic release behavior and enhanced PPN permeation. The in vitro antioxidant study results showed a comparable antioxidant activity with pure PPN. The anticancer study depicted that the cell viability assay of tested PLF3C2 has significantly (p < 0.001)) reduced the IC50 when compared with pure PPN. The study revealed that oral chitosan-coated liposomes are a promising delivery system for the PPN and can increase the therapeutic efficacy against the breast cancer cell line.

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A Nitrocarbazole as a New Microtubule-Targeting Agent in Breast Cancer Treatment

Applied Sciences ◽

10.3390/app11199139 ◽

2021 ◽

Vol 11 (19) ◽

pp. 9139

Author(s):

Maria Stefania Sinicropi ◽

Cinzia Tavani ◽

Camillo Rosano ◽

Jessica Ceramella ◽

Domenico Iacopetta ◽

...

Keyword(s):

Breast Cancer ◽

Anticancer Activity ◽

Breast Cancer Cell Lines ◽

Cellular Functions ◽

Anticancer Properties ◽

Cycle Arrest ◽

In Silico Studies ◽

Ic50 Values ◽

Mcf 7

Breast cancer is still considered a high-incidence disease, and numerous are the research efforts for the development of new useful and effective therapies. Among anticancer drugs, carbazole compounds are largely studied for their anticancer properties and their ability to interfere with specific targets, such as microtubule components. The latter are involved in vital cellular functions, and the perturbation of their dynamics leads to cell cycle arrest and subsequent apoptosis. In this context, we report the anticancer activity of a series of carbazole analogues 1–8. Among them, 2-nitrocarbazole 1 exhibited the best cytotoxic profile, showing good anticancer activity against two breast cancer cell lines, namely MCF-7 and MDA-MB-231, with IC50 values of 7 ± 1.0 and 11.6 ± 0.8 μM, respectively. Furthermore, compound 1 did not interfere with the growth of the normal cell line MCF-10A, contrarily to Ellipticine, a well-known carbazole derivative used as a reference molecule. Finally, in vitro immunofluorescence analysis and in silico studies allowed us to demonstrate the ability of compound 1 to interfere with tubulin organization, similarly to vinblastine: a feature that results in triggering MCF-7 cell death by apoptosis, as demonstrated using a TUNEL assay.

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In Vivo and In Vitro Evaluation of the Protective Effects of Hesperidin in Lipopolysaccharide-Induced Inflammation and Cytotoxicity of Cell

Molecules ◽

10.3390/molecules25030478 ◽

2020 ◽

Vol 25 (3) ◽

pp. 478 ◽

Cited By ~ 6

Author(s):

Rasha Al-Rikabi ◽

Hanady Al-Shmgani ◽

Yaser Hassan Dewir ◽

Salah El-Hendawy

Keyword(s):

Breast Cancer ◽

Chromatin Condensation ◽

Control Group ◽

Potential Candidate ◽

Dependent Manner ◽

Protective Effects ◽

Mcf7 Cells ◽

Tnf Α

(1) Background: Plant flavonoids are efficient in preventing and treating various diseases. This study aimed to evaluate the ability of hesperidin, a flavonoid found in citrus fruits, in inhibiting lipopolysaccharide (LPS) induced inflammation, which induced lethal toxicity in vivo, and to evaluate its importance as an antitumor agent in breast cancer. The in vivo experiments revealed the protective effects of hesperidin against the negative LPS effects on the liver and spleen of male mice. (2) Methods: In the liver, the antioxidant activity was measured by estimating the concentration of glutathione (GSH) and catalase (CAT), whereas in spleen, the concentration of cytokines including IL-33 and TNF-α was measured. The in vitro experiments including MTT assay, clonogenity test, and sulforhodamine 101 stain with DAPI (4′, 6-diamidino-2-phenylindole) were used to assess the morphological apoptosis in breast cancer cells. (3) Results: The results of this study revealed a significant increase in the IL-33 and TNF-α cytokine levels in LPS challenged mice along with a considerable elevation in glutathione (GSH); moreover, the catalase (CAT) level was higher compared to that of the control group. Cytotoxicity of the MCF-7 cell line revealed significant differences among the groups treated with different concentrations when compared to the control groups, in a concentration-dependent manner. Hesperidin significantly inhibited the colony formation of MCF7 cells when compared to that of control. Clear changes were observed in the cell shape, including cell shrinkage and chromatin condensation, which were associated with a later apoptotic stage. (4) Conclusion: The results indicate that hesperidin might be a potential candidate in preventing diseases.

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Safety and long-term maintenance of anti-HER2 immunity following booster inoculations of the E75 breast cancer vaccine.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.2529 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 2529-2529

Author(s):

Raetasha Sheavette Dabney ◽

Diane F Hale ◽

Timothy J Vreeland ◽

Guy T. Clifton ◽

Alan K. Sears ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Vaccine ◽

Peptide Vaccine ◽

Control Group ◽

Breast Cancer Patients ◽

Recurrence Rates ◽

Specific Immunity

2529 Background: We have completed accrual and are in the follow up portion of phase I/II clinical trials evaluating the E75 HER2 peptide vaccine. E75 has been proven safe, capable of stimulating HER2 immunity, and effective in decreasing breast cancer recurrence rates. During the conduct of this trial, it was noted that E75-specific immunity waned after the Primary Vaccine Series (PVS) which corresponded with late recurrences. To maintain long-term immunity, a voluntary booster program was started. Here we present analysis of the booster inoculations. Methods: The trial enrolled node-positive or high-risk, node-negative breast cancer patients (pts) with tumors expressing any level of HER2 (IHC 1-3+). HLA-A2/A3+ pts comprised the vaccine group (VG), HLA-A2/A3- pts were followed as the control group (CG). The VG received 4-6 monthly inoculations of E75+GM-CSF. Volunteer booster program pts (BG) received inoculations every 6 months after the PVS. Pts were monitored for toxicities, in vivo responses by local reactions (LR) and DTH, and in vitro responses measured by enumeration of E75 specific cytotoxic T lymphocytes. Results: 53 pts received at least 1 booster, 34 received 2, 24 three, 20 four, 12 five, and 8 at least 6. 24% of pts had no local toxicity, 73% Grade 1 (G1), 3% G2. 74% had no systemic toxicity, 35% G1, 1% G2. LRs increased significantly from the initial vaccine (R1) during PVS to each booster (B) (R1: 59.5±3.1 v B1: 89.2±3.3, p<0.001; v B2: 95.15±5, p<0.001; v B3: 86.63±5.5, p<0.001; v B4: 83.26±4.6, p=<0.001; v B5: 80.67±6.7, p=0.006; v B6: 78.75±9.4, p=0.04). Dimer values increased from the end of PVS to each post-booster value (pre B1:1.29±0.25 v post B1: 1.46±0.38; post B2: 1.41±0.4; post B3: 1.84±0.35; post B4: 2.23±0.4; post B5:1.94±0.31; post B6: 2.73±0.09, p=0.02). At median 60 months, the recurrence rate for BG was 3.8% vs 18.9% in the CG (p=0.01). Conclusions: Booster inoculations are well-tolerated and appear to assist in the maintenance of long term peptide-specific immunity. Boosted pts have improved recurrence rates. Based on the success of this program, we have incorporated the practice of booster inoculations in our current cancer vaccine trials.

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Biomarker correlation to clinical response in phase I/II trials of the adjuvant breast cancer vaccine neuvax (nelipepimut-S or E75).

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.tps3126 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. TPS3126-TPS3126

Author(s):

John S. Berry ◽

Alfred F Trappey ◽

Alan K. Sears ◽

Timothy J Vreeland ◽

Guy T. Clifton ◽

...

Keyword(s):

Breast Cancer ◽

Phase I ◽

Peptide Vaccine ◽

Clonal Expansion ◽

Mean Difference ◽

Control Group ◽

Breast Cancer Patients ◽

Clinical Recurrence ◽

The Mean

TPS3126 Background: We completed phase I/II clinical trials with NeuVax (nelipepimut-S), a HLA-A2/A3-restricted, HER2-derived peptide vaccine. The vaccine was administered in the adjuvant setting to prevent recurrence in breast cancer patients rendered disease-free with standard-of-care therapy. Here, we examine the relationship between in vitro immunologic response (IR) and clinical recurrence (CR) after 5-year follow-up. Methods: The phase I/II trials were performed as dose-escalation/schedule-optimization trials enrolling node positive and high-risk, node-negative patients (pts) with tumors expressing any level of HER2 (IHC 1+,2+,or 3+). HLA-A2/A3+ pts were enrolled in the vaccine group (VG) while HLA-A2/A3- pts were followed prospectively as an untreated control group (CG). The VG was given 4-6 monthly intradermal inoculations of nelipepimut-S+GMCSF (immunoadjuvant) during the primary vaccine series (PVS). In vitro IR was assessed for E75-specific, cytotoxic T lymphocyte clonal expansion by HLA-A2:IgG dimer assay and expressed as mean dimer index (mdi) at baseline, after PVS (R6), and six months after the PVS. HER2 under-expression was defined as an IHC 1/2, and a FISH < 2.2. VG and CG pts were followed for CR over 60 months. P-values were calculated using the Fisher’s exact test. Results: Of the 195 pts enrolled, 8 withdrew, leaving 187 evaluable pts; 108 in the VG and 79 in the CG. R6 dimer assays were available for 86 pts in the VG. The mean R6 dimer in the VG is 0.63 mdi+.08. Of the 30 pts with an R6 dimer above the mean, only one recurred, compared to eight of the 56 below the mean (p=.09). The difference between baseline and maximum mdi was available in 56 HER2 under-expressing VG pts. Of the 26 pts above the mean difference (1.08 mdi +.17), one recurred, compared to six CR in the 30 pts below the mean (p=.06). There were no CR in pts with HER2 under expression with a mean difference ranked in the top third. Conclusions: In prospective, completed phase I/II trials of NeuVax (nelipepimut-S), patients who exhibit robust in vitro IR have lower recurrence rates. This finding suggests that nelipepimut-specific CTL clonal expansion is a valid biomarker for CR in pts treated with NeuVax. Clinical trial information: NCT00841399.

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Non-Platinum Metal Complexes as Potential Anti-Triple Negative Breast Cancer Agents

Crystals ◽

10.3390/cryst8100369 ◽

2018 ◽

Vol 8 (10) ◽

pp. 369 ◽

Cited By ~ 4

Author(s):

Eva Domínguez-Martís ◽

Diego Mosteiro-Miguéns ◽

Lucía Vigo-Gendre ◽

David López-Ares ◽

Manuel Freire-Garabal ◽

...

Keyword(s):

Breast Cancer ◽

Triple Negative ◽

Platinum Metal ◽

Chemotherapy Drugs ◽

Anticancer Properties ◽

Current Therapies ◽

Platinum Metal Complexes ◽

Platinum Chemotherapy

Breast cancer (BC) is the most common cancer in women worldwide, with a mortality rate that has been forecasted to rise in the next decade. This is especially worrying for people with triple-negative BC (TNBC), because of its unresponsiveness to current therapies. Different drugs to treat TNBC have been assessed, and, although platinum chemotherapy drugs seem to offer some hope, their drawbacks have motivated extensive investigations into alternative metal-based BC therapies. This paper aims to: (i) describe the preliminary in vitro and in vivo anticancer properties of non-platinum metal-based complexes (NPMBC) against TNBC; and (ii) analyze the likely molecular targets involved in their anticancer activity.

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Evaluation of Anti-Tumor Potential of Lactobacillus acidophilus ATCC4356 Culture Supernatants in MCF-7 Breast Cancer

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520621666201207085239 ◽

2020 ◽

Vol 21 ◽

Author(s):

Ramazan Behzadi ◽

Ahmad Hormati ◽

Karim Eivaziatashbeik ◽

Sajjad Ahmadpour ◽

Fatemeh Khodadust ◽

...

Keyword(s):

Breast Cancer ◽

Nude Mice ◽

Control Group ◽

Bacterial Strains ◽

Anti Cancer ◽

99Mtc Mibi ◽

Culture Supernatants ◽

Mcf 7

Background: Anti-cancer activity of some lactic acid bacterial strains is well documented in several literatures. Lactobacillus strains have received considerable attention as a beneficial microbiota. The aim of this study is to evaluate the effects of anti-tumor activities of L. acidophilus ATCC4356 culture supernatants on the MCF-7 human breast cancer cells. Materials and methods: Anti-cancer effect of 24h and 48h culture supernatants at various concentrations (1.25, 2.5, 5, 10 and 20 µg/ml) were determined by various in vitro and in vivo assays including MTT, tumor volume measurement as well as 99mTc-MIBI biodistribution in MCF-7 tumor bearing nude mice and histopathology test. For evaluation of the related mechanism of action, quantitative PCR was conducted. Results: The 48h culture supernatants at 10 and 20 µg/ml exhibited significant in vitro inhibition of MCF-7 cell proliferation. However, this inhibition was not observed for HUVEC human endothelial normal cells. Q-PCR indicated that treatment by the supernatant led to a significant downregulation of VEGFR ( ̴ 0.009 fold) and Bcl-2 ( ̴ 0.5 fold) and upregulation of p53 ( ̴ 1.3 fold). In vivo study using MCF-7 xenograft mouse models demonstrated reduction in tumor weight and volume by both 24h and 48h supernatants (10 µg/ml and 20 µg/ml) after 15 days. According to the 99mTc-MIBI biodistribution result, treatment of MCF-7 bearing nude mice with both 24h and 48h supernatant (20 µg/ml) led to significant decrease in tumor uptake compared with the control group. Conclusion: These results suggest that the culture supernatants of L. acidophilus ATCC4356 at suitable concentrations can be considered as a good alternative nutraceutical with promising therapeutic indexes for breast cancer.

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In VitroCytotoxicity andIn VivoAntimammary Tumor Effects of the Hydroethanolic Extract ofAcacia seyal(Mimosaceae) Stem Bark

BioMed Research International ◽

10.1155/2018/2024602 ◽

2018 ◽

Vol 2018 ◽

pp. 1-13 ◽

Cited By ~ 5

Author(s):

Stephane Zingue ◽

Amstrong Nang Njuh ◽

Alain Brice Tueche ◽

Jeremie Tamsa ◽

Edwige Nana Tchoupang ◽

...

Keyword(s):

Breast Cancer ◽

Mammary Tumors ◽

Stem Bark ◽

Control Group ◽

Dependent Manner ◽

Antitumor Effects ◽

Hydroethanolic Extract ◽

Acacia Seyal

The present study was designed to evaluate thein vitroandin vivoantitumor effects ofA. seyalhydroethanolic extract on breast cancer. The cytotoxicity ofA. seyalextract was evaluated using resazurin reduction assay in 9 cell lines. Further, the protective effect of the hydroethanolic extract ofA. seyalstem barks was evaluated on 7,12-dimethylbenz(a)anthracene- (DMBA-) induced breast cancer rat model. Incidence, burden, volume, and histological analysis of mammary tumors were measured. TheAcacia seyalextract exhibited CC50of 100 in MCF-7 cells after 24 h.In vivo, no tumors were detected in rats from the control group, while 11 rats out of 12 (91.66%) developed mammary tumors in the DMBA-exposed group receiving only the vehicle.Acacia seyalextract significantly (p<0.01) and in the dose-dependent manner reduced tumor incidence (3 rats out of 12 at the dose of 300 mg/kg), burden [62.1% (150 mg/kg) and 65.8% (300 mg/kg)], and mass. It protected rats against DMBA-induced breast hyperplasia, with an optimal effect at the dose of 300 mg/kg. Taken altogether, these results suggest that the hydroethanolic extract ofAcacia seyalmight contain phytoconstituents endowed with antitumoral properties, which could protect against the breast cancer induced in rats.

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mir-556-3p Promotes the Progression of Breast Cancer Through Targeting Disabled Gene Homolog 2 Interacting Protein (DAB2IP)

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2021.2848 ◽

2021 ◽

Vol 11 (12) ◽

pp. 2472-2477

Author(s):

Chunxiong Fan ◽

Yanping Deng ◽

Yaqing Liu ◽

Xiaoying Liu ◽

Xi Ke ◽

...

Keyword(s):

Breast Cancer ◽

Cell Proliferation ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Cell Activity ◽

Control Group ◽

Cancer Tissue ◽

Breast Cancer Patients ◽

Cancer Pathogenesis

Our study assessed miR-556-3p’s role in breast cancer cells. A total of 65 cases of breast cancer tissue samples were retrospectively analyzed to detect miR-556-3p level by PCR and analyze survival time and 30 normal breast tissues were included as a control group. Breast cancer cells were cultured followed by analysis of cell proliferation by MTT, cell invasion by transwell assay. miR-556-3p level was significantly upregulated in breast cancer patients compared to control group (P <0.05) and inversely associated with survival rate (P <0.05). In vitro experiments, cell activity and invasion were positively correlated with miR-556-3p level (P <0.05). In MCF-7 cell lines, miR-556-3p overexpression increased cell activity (P <0.05). Meanwhile, after miR-556-3p was overexpressed, the expression of DAB2IP, Erk, p-Erk in breast cancer cells was significantly reduced and increased after miR-556-3p was knocked down. In conclusion, miR-556-3p targets DAB2IP3′-UTR, promotes breast cancer cell proliferation, indicating that miR-556-3p might be involved in breast cancer pathogenesis and may be a new target for the treatment.

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