Modulation of pro-apoptotic effects and mitochondrial potential on B16F10 cells by DODAC/PHO-S liposomes

Luna, Arthur Cássio de Lima; Filho, José Roberto de Assis Santos; Hesse, Henrique; Neto, Salvador Claro; Chierice, Gilberto Orivaldo; Maria, Durvanei Augusto

doi:10.1186/s13104-018-3170-7

Cited by 8 publications

(13 citation statements)

References 12 publications

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“…Another study reported the encapsulation of phosphoethanolamine (PHO-S, Figure 13), a phosphoric ester, into cationic liposomes (Table 3, C13). This nanoformulation demonstrated high cytotoxic activity towards B16F10 melanoma cells, compared with free compound, through induction of G 2 /M-phase cell cycle arrest (Table 4, F11) [185], as well as modulation of the expression of pro-apoptotic proteins (Table 4, F12) [186].…”

Section: Nanotechnology and Cancer Treatment—tackling Melanomamentioning

confidence: 99%

Emergent Nanotechnological Strategies for Systemic Chemotherapy against Melanoma

2019

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Melanoma is an aggressive form of skin cancer, being one of the deadliest cancers in the world. The current treatment options involve surgery, radiotherapy, targeted therapy, immunotherapy and the use of chemotherapeutic agents. Although the last approach is the most used, the high toxicity and the lack of efficacy in advanced stages of the disease have demanded the search for novel bioactive molecules and/or efficient drug delivery systems. The current review aims to discuss the most recent advances on the elucidation of potential targets for melanoma treatment, such as aquaporin-3 and tyrosinase. In addition, the role of nanotechnology as a valuable strategy to effectively deliver selective drugs is emphasized, either incorporating/encapsulating synthetic molecules or natural-derived compounds in lipid-based nanosystems such as liposomes. Nanoformulated compounds have been explored for their improved anticancer activity against melanoma and promising results have been obtained. Indeed, they displayed improved physicochemical properties and higher accumulation in tumoral tissues, which potentiated the efficacy of the compounds in pre-clinical experiments. Overall, these experiments opened new doors for the discovery and development of more effective drug formulations for melanoma treatment.

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Section: Nanotechnology and Cancer Treatment—tackling Melanomamentioning

confidence: 99%

Emergent Nanotechnological Strategies for Systemic Chemotherapy against Melanoma

2019

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“…The analysis of protein expression were performed as previously published [ 15 , 16 ]. In brief, the Hepa1c1c7 cells (1 × 10 5 cells/well, the cell density reached 80 to 90% confluence), were treated with PHO-S (0.3–2.0 mM), DODAC/PHO-S 1:1 (0.3–2.0 mM), and empty DODAC (0.3–2.0 mM), for 12 h, were washed with PBS and resuspended in FACS buffer with 2.5% paraformaldehyde for 1 h. After washing, cells were again resuspended in a primary antibody specific for the proteins anti-CD44, anti-CD90, anti-p53, anti-p21, anti-p27, anti-Bax, anti-Bcl-2, anti-caspase-3, anti-caspase-8 (Abcam, Cambridge, MA, United States); anti- cytochrome c, anti-DR4 (Santa (Cruz Biotechnology Inc., Santa Cruz, EUA) and anti-cyclin D1 (Cell Signaling Technology, Danvers, MA), at a concentration of 1 μg/ml at 4 °C, for 1 min.…”

Section: Methodsmentioning

confidence: 99%

“…The Hepa1c1c7 cells were plated on sterile glass slides in 24-well plates, at concentration of 10 5 . After 24 h, the cells were treated with PHO-S and DODAC/PHO-S (1:1) at 0.3 and 2.0 mM, for 6 h. Then, the incubation with rhodamine-123 and analyses were perfomed as previously published [ 15 , 16 ].…”

Section: Methodsmentioning

confidence: 99%

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Antiproliferative and proapoptotic effects of DODAC/synthetic phosphoethanolamine on hepatocellular carcinoma cells

Luna

Saraiva

Chierice

et al. 2018

BMC Pharmacol Toxicol

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BackgroundCurrent studies have demonstrated that DODAC/PHO-S (Dioctadecyldimethylammonium Chloride/Synthetic phosphoethanolamine) liposomes induces cytotoxicity in Hepa1c1c7 and B16F10 murine tumor cells, with a higher proportion than PHO-S. Therefore, our aim was to evaluate the potential of DODAC/PHO-S to elucidate the mechanism of cell death whereby the liposomes induces cytotoxicity in hepatocellular carcinoma Hepa1c1c7, compared to the PHO-S alone.MethodsLiposomes (DODAC/PHO-S) were prepared by ultrasonication. The cell cycle phases, protein expression and types of cell’s death on Hepa1c1c7 were analyzed by flow cytometry. The internalisation of liposomes, mitochondrial electrical potential and lysosomal stability were also evaluated by confocal laser scanning microscopy.ResultsAfter treatment with liposomes (DODAC/PHO-S), we observed a significant increase in the population of Hepa1c1c7 cells experiencing cell cycle arrest in the S and G2/M phases, and this treatment was significantly more effective to promote cell death by apoptosis. There also was a decrease in the mitochondrial electrical potential; changes in the lysosomes; nuclear fragmentation and catastrophic changes in Hepa1c1c7 cells. The liposomes additionally promoted increases in the expression of DR4 receptor, caspases 3 and 8, cytochrome c, p53, p21, p27 and Bax. There was also a decrease in the expression of Bcl-2, cyclin D1, CD90 and CD44 proteins.ConclusionThe overall results showed that DODAC/PHO-S liposomes were more effective than PHO-S alone, in promoting cytotoxicity Hepa1c1c7 tumor cells, activating the intrinsic and extrinsic pathways of programmed cell death.

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“…With this aim, our group has expressed interest in exploring the activity of 2-aminoethyl dihydrogen phosphate (2-AEH2P) as a therapeutic adjuvant through in vitro and in vivo studies involving various types of cancer. Indeed, 2-AEH2P has modulated proliferative and apoptotic effects in human breast cancer cells with estrogen, progesterone, and glucocorticoid receptors (MCF-7) [24], in triple-negative breast cancer cells (MDA-MB-231) [25], murine melanoma (B16-F10) [26], K-562 and K-562 MDR(+) myeloid leukemia [27], and murine hepatoma (Hepa-1c1c7) [28], indicating significant data in these cell lines regarding the reduction of mitochondrial membrane potential and the expression of markers involved in cell death, angiogenesis, and proliferation. In turn, paclitaxel (PTX) is a widely used chemotherapy agent in the treatment of advanced metastatic breast cancer [29].…”

Section: Introductionmentioning

confidence: 99%

2-Aminoethyl Dihydrogen Phosphate (2-AEH2P) Associated with Cell Metabolism-Modulating Drugs Presents a Synergistic and Pro-Apoptotic Effect in an In Vitro Model of the Ascitic Ehrlich Tumor

Alves,

Cabral,

Totti

et al. 2024

Biomedicines

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The progression and maintenance of cancer characteristics are associated with cellular components linked to the tumor and non-cellular components with pro-tumoral properties. Pharmacological association with antagonists of the cellular components of the tumor, such as anti- and pro-apoptotic drugs, represents a novel adjuvant strategy. In this study, the antiproliferative, pro-apoptotic, and pharmacological effects of the combination of monophosphoester 2-AEH2P with Simvastatin, Coenzyme Q10, the chemotherapeutic drug paclitaxel, and colony-stimulating factor (GM-CSF) were evaluated. Tests were conducted to determine cytotoxic activity using the MTT method, cell cycle phases, and fragmented DNA by flow cytometry, mitochondrial membrane potential, expression of cell markers Bcl2, TNF-α/DR-4, Cytochrome c, caspase 3, and P53, and analysis of drug combination profiles using Synergy Finder 2.0 Software. The results showed a synergistic effect among the combinations, compared to individual treatments with the monophosphoester and other drugs. In addition, there was modulation of marker expression, indicating a pro-apoptotic and immunomodulatory effect of 2-AEH2P. Pharmacological analysis revealed that tumor cells treated with GM-CSF + 2-AEH2P exhibited a synergistic effect, while groups of tumor cells treated with paclitaxel, Coenzyme Q10, and Simvastatin showed additive effects. Furthermore, treatment with the paclitaxel + 2-AEH2P combination (12 h) resulted in a significant reduction in mitochondrial membrane potential. Pharmacological combinations for normal cells did not exhibit deleterious effects compared to mammary carcinomatosis tumor (EAT) cells.

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Modulation of pro-apoptotic effects and mitochondrial potential on B16F10 cells by DODAC/PHO-S liposomes

Cited by 8 publications

References 12 publications

Emergent Nanotechnological Strategies for Systemic Chemotherapy against Melanoma

Emergent Nanotechnological Strategies for Systemic Chemotherapy against Melanoma

Antiproliferative and proapoptotic effects of DODAC/synthetic phosphoethanolamine on hepatocellular carcinoma cells

2-Aminoethyl Dihydrogen Phosphate (2-AEH2P) Associated with Cell Metabolism-Modulating Drugs Presents a Synergistic and Pro-Apoptotic Effect in an In Vitro Model of the Ascitic Ehrlich Tumor

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