Synergistic Effect of Doxorubicin and siRNA-Mediated Silencing of Mcl-1 Using Cationic Niosomes against 3D MCF-7 Spheroids

Pengnam, Supusson; Plianwong, Samarwadee; Patrojanasophon, Prasopchai; Radchatawedchakoon, Widchaya; Yingyongnarongkul, Boon‐ek; Opanasopit, Praneet; Charoensuksai, Purin

doi:10.3390/pharmaceutics13040550

Cited by 19 publications

(15 citation statements)

References 67 publications

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“…al. [23] but they showed no effective response (i.e., cell killing) with Mcl-1 and survivin siRNAs in MDA-MB-231 cells using a delivery system of cationic niosomes (PCN-B). The positive results reported in this study were presumably due to better siRNA transfection e ciency achieved by the speci c transfection reagents employed.…”

Section: Discussionmentioning

confidence: 99%

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Improved delivery of Mcl-1 and survivin siRNA combination in breast cancer cells with additive siRNA complexes

et al. 2022

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This study aimed at investigating the in uence of commercial transfection reagents (Prime-Fect, Leu-Fect A, and Leu-Fect C) complexed with different siRNAs (CDC20, HSP90, Mcl-1 and Survivin) in MDA-MB-436 breast cancer cells and the impact of incorporating an anionic additive, Trans-Booster, for improving in vitro gene silencing and delivery e ciency. Gene silencing was quantitatively analyzed by real-time RT-PCR while cell proliferation and siRNA uptake were evaluated by the MTT assay and ow cytometry, respectively. Amongst the investigated siRNAs and transfection reagents, Mcl-1/Prime-Fect complexes showed the highest inhibition of cell viability and most effective siRNA delivery. The effect of various formulations on transfection e ciency showed that a anionic additive with 1:1 ratio with siRNA was optimal achieving the lowest cell viability compared to untreated cells and negative control siRNA treatment (p<0.05). Furthermore, the combination of Mcl-1 and survivin siRNA suppressed the growth of MDA-MB-436 cells more effectively than treatment with the single siRNAs and resulted in a cell viability as low as ~20% (vs. non-treated cells). This aligned well with the induction of apoptosis as analyzed by ow cytometry, which revealed higher apoptotic cells with the combination treatment group. We conclude that commercial transfection reagents formulated with Mcl-1/Survivin siRNA combination could serve as a potent anti-proliferation agent in treatment of breast cancers.

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Section: Discussionmentioning

confidence: 99%

“…(2019) developed a protocol for identi cation of synergistic combinations of Mcl-1 siRNA and chemotherapy drugs using siRNA libraries to overcome the limitations of single agent therapies [35] . Pengnam et. al.…”

Section: Introductionmentioning

confidence: 99%

Improved delivery of Mcl-1 and survivin siRNA combination in breast cancer cells with additive siRNA complexes

et al. 2022

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“…In addition, the same experiments with each flavanone (ERI, NER, HED, NHE, and HET) at the same concentrations (5, 7.5, 10, and 20 µM) used in the combination experiments were carried out as a control. The activity values obtained for all assays, expressed as percentages, and converted into the fraction of effect (Fa) according to the following equation: Fa = 100% of activity/100, were used for the calculation of the synergism using CompuSyn software Version 1.0 (ComboSyn, Inc., Paramus, NJ, USA) [ 40 ]. The data points, including treatment concentrations (µM) and Fa, were automatically processed.…”

Section: Methodsmentioning

confidence: 99%

Synergistic Combination of Citrus Flavanones as Strong Antioxidant and COX-Inhibitor Agent

et al. 2023

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Recently, we demonstrated that a Citrus flavanone mix (FM) shows antioxidant and anti-inflammatory activity, even after gastro-duodenal digestion (DFM). The aim of this study was to investigate the possible involvement of the cyclooxygenases (COXs) in the anti-inflammatory activity previously detected, using a human COX inhibitor screening assay, molecular modeling studies, and PGE2 release by Caco-2 cells stimulated with IL-1β and arachidonic acid. Furthermore, the ability to counteract pro-oxidative processes induced by IL-1β was evaluated by measuring four oxidative stress markers, namely, carbonylated proteins, thiobarbituric acid-reactive substances, reactive oxygen species, and reduced glutathione/oxidized glutathione ratio in Caco-2 cells. All flavonoids showed a strong inhibitory activity on COXs, confirmed by molecular modeling studies, with DFM, which showed the best and most synergistic activity on COX-2 (82.45% vs. 87.93% of nimesulide). These results were also corroborated by the cell-based assays. Indeed, DFM proves to be the most powerful anti-inflammatory and antioxidant agent reducing, synergistically and in a statistically significant manner (p < 0.05), PGE2 release than the oxidative stress markers, also with respect to the nimesulide and trolox used as reference compounds. This leads to the hypothesis that FM could be an excellent antioxidant and COX inhibitor candidate to counteract intestinal inflammation.

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“…116 These studies highlight the fact that codelivery of synthetic molecules and genetic tools can effectively suppress breast cancer progression. [157][158][159][160] It is also worth mentioning that codelivery of genetic tools and phytochemicals in synergistic breast cancer therapy is followed. An experiment developed hybrid lipid nanoparticles for codelivery of IGF-1R and lycopene in breast cancer therapy.…”

Section: Drug and Gene Codeliverymentioning

confidence: 99%

(Nano)platforms in breast cancer therapy: Drug/gene delivery, advanced nanocarriers and immunotherapy

Ashrafizadeh

Zarrabi

Bigham

et al. 2023

Medicinal Research Reviews

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Breast cancer is the most malignant tumor in women, and there is no absolute cure for it. Although treatment modalities including surgery, chemotherapy, and radiotherapy are utilized for breast cancer, it is still a life‐threatening disease for humans. Nanomedicine has provided a new opportunity in breast cancer treatment, which is the focus of the current study. The nanocarriers deliver chemotherapeutic agents and natural products, both of which increase cytotoxicity against breast tumor cells and prevent the development of drug resistance. The efficacy of gene therapy is boosted by nanoparticles and the delivery of CRISPR/Cas9, Noncoding RNAs, and RNAi, promoting their potential for gene expression regulation. The drug and gene codelivery by nanoparticles can exert a synergistic impact on breast tumors and enhance cellular uptake via endocytosis. Nanostructures are able to induce photothermal and photodynamic therapy for breast tumor ablation via cell death induction. The nanoparticles can provide tumor microenvironment remodeling and repolarization of macrophages for antitumor immunity. The stimuli‐responsive nanocarriers, including pH‐, redox‐, and light‐sensitive, can mediate targeted suppression of breast tumors. Besides, nanoparticles can provide a diagnosis of breast cancer and detect biomarkers. Various kinds of nanoparticles have been employed for breast cancer therapy, including carbon‐, lipid‐, polymeric‐ and metal‐based nanostructures, which are different in terms of biocompatibility and delivery efficiency.

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Synergistic Effect of Doxorubicin and siRNA-Mediated Silencing of Mcl-1 Using Cationic Niosomes against 3D MCF-7 Spheroids

Cited by 19 publications

References 67 publications

Improved delivery of Mcl-1 and survivin siRNA combination in breast cancer cells with additive siRNA complexes

Improved delivery of Mcl-1 and survivin siRNA combination in breast cancer cells with additive siRNA complexes

Synergistic Combination of Citrus Flavanones as Strong Antioxidant and COX-Inhibitor Agent

(Nano)platforms in breast cancer therapy: Drug/gene delivery, advanced nanocarriers and immunotherapy

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