Effect of sodium dichloroacetate as single agent or in combination with cisplatin in normal and human cervical cancer cell lines

Purpose: To evaluate the synergistic cytotoxicity of sodium dichloroacetate (DCA) in combination with cisplatin (CIS) against human cervical cancer cell lines. Methods: Cervical cancer SiHa and HeLa cells and normal cells (Hek-293, Vero, peripheral blood mononuclear and human erythrocytes) were treated in vitro with DCA and CIS individually or their combination. Cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method while hemolytic activity was evaluated from the released hemoglobin. Halfmaximal inhibitory concentration (IC50) of DCA or CIS was obtained. Results: The combination of DCA + CIS decreased the cell viability of SiHa, Hek-293, Vero, and PBMC cells, but not of Hela cells (p < 0.05). Furthermore, the individual treatments alone or in combination did not cause significant hemolysis (p < 0.05). Conclusion: The combination of DCA + CIS increases the damage caused by CIS alone on SiHa cells. It also decreases the cell viability of Hek-293 and Vero without affecting peripheral blood mononuclear and human erythrocyte integrity. The results suggest that the combination of DCA and CIS can induce synergistic antitumor effect in different types of cancer cell lines. However, further studies are required to determine the biological effects of the combination of DCA and CIS in vivo. Keywords: Cervical cancer, Sodium dichloroacetate, Cisplatin, Viability, Hemolysi

In vitro Evaluation of Phthalimide Derivatives Against Cancer Cell lines

Los cánceres de pulmón, próstata e hígado se encuentran entre los más prevalentes en los hombres. El cáncer de mama, de cuello uterino y de tiroides se encuentran entre los más prevalentes en mujeres (OMS, 2019). El tratamiento del cáncer generalmente incluye quimioterapia y radioterapia; sin embargo, los medicamentos contra el cáncer disponibles tienen una selectividad baja y causan efectos adversos graves, como nefrotoxicidad, neurotoxicidad y mielosupresión (Matsuo et al., 2010). Por tanto, el diseño y desarrollo de compuestos como nuevos agentes anticancerígenos frente a los tipos de cáncer de mayor incidencia son de vital importancia en el campo de la salud. Los derivados de ftalimida son compuestos prometedores para el desarrollo de nuevos agentes anticancerígenos (Li et al., 2011; Grigalius y Petrikaite, 2017; Kamal et al., 2002). Basado en lo anterior, Este trabajo tuvo como objetivo evaluar la actividad antiproliferativa de 43 derivados de ftalimida contra una línea celular de cáncer principal en hombres (HepG2) y dos líneas celulares de cáncer principales en mujeres (HeLa y 4T1). Además, se determinó la citotoxicidad de los compuestos contra una línea celular de fibroblasto murino normal (3T3). Los resultados mostraron que los compuestos C16, E11 y E16 presentaron la mejor actividad antiproliferativa contra las líneas celulares HeLa y 4T1. El compuesto H16 solo disminuyó la proliferación celular en un 32% contra la línea celular HepG2. Los compuestos H5, H16, E2, E16 y C1 no afectaron a la proliferación de la línea celular 3T3. Demostrando que sería importante continuar con el análisis de este tipo de compuestos frente a diferentes cánceres para encontrar nuevos compuestos con mejor actividad que los actualmente disponibles en el mercado

Silencing of Foxp3 delays the growth of murine melanomas and modifies the tumor immunosuppressive environment

Forkhead box p3 (Foxp3) expression was believed to be specific for T-regulatory cells but has recently been described in non-hematopoietic cells from different tissue origins and in tumor cells from both epithelial and non-epithelial tissues. The aim of this study was to elucidate the role of Foxp3 in murine melanoma. The B16F10 cell line Foxp3 silenced with small interference Foxp3 plasmid transfection was established and named B16F10.1. These cells had lower levels of Foxp3 mRNA (quantitative real-time reverse transcription-polymerase chain reaction [0.235-fold]), protein (flow cytometry [0.02%]), CD25(+) expression (0.06%), cellular proliferation (trypan blue staining), and interleukin (IL)-2 production (enzyme-linked immunosorbent assay [72.35 pg/mL]) than those in B16F10 wild-type (WT) cells (P<0.05). Subcutaneous inoculation of the B16F10.1 cell line into C57BL/6 mice delayed the time of visible tumor appearance, increased the time of survival, and affected the weight of tumors, and also decreased the production of IL-10, IL-2, and transforming growth factor beta compared with mice inoculated with the B16F10 WT cell line. The B16F10.1 cells derived from tumors and free of T-cells (isolated by Dynabeads and plastic attachment) expressed relatively lower levels of Foxp3 and CD25(+) than B16F10 WT cells (P<0.05) in a time-dependent manner. The population of tumor-infiltrating lymphocytes of T CD4(+) cells (CD4(+), CD4(+)CD25(+), and CD4(+)CD25(+)Foxp3(+)) increased in a time-dependent manner (P<0.05) in tumors derived from B16F10 WT cells and decreased in tumors derived from B16F10.1 cells. Similar data were obtained from spleen cells. These results suggest that, in melanomas, Foxp3 partly induces tumor growth by modifying the immune system at the local and peripheral level, shifting the environment toward an immunosuppressive profile. Therapies incorporating this transcription factor could be strategies for cancer treatment

Antitumor activity of colloidal silver on MCF-7 human breast cancer cells

<p>Abstract</p> <p>Background</p> <p>Colloidal silver has been used as an antimicrobial and disinfectant agent. However, there is scarce information on its antitumor potential. The aim of this study was to determine if colloidal silver had cytotoxic effects on MCF-7 breast cancer cells and its mechanism of cell death.</p> <p>Methods</p> <p>MCF-7 breast cancer cells were treated with colloidal silver (ranged from 1.75 to 17.5 ng/mL) for 5 h at 37°C and 5% CO₂atmosphere. Cell Viability was evaluated by trypan blue exclusion method and the mechanism of cell death through detection of mono-oligonucleosomes using an ELISA kit and TUNEL assay. The production of NO, LDH, and Gpx, SOD, CAT, and Total antioxidant activities were evaluated by colorimetric assays.</p> <p>Results</p> <p>Colloidal silver had dose-dependent cytotoxic effect in MCF-7 breast cancer cells through induction of apoptosis, shown an LD₅₀(3.5 ng/mL) and LD₁₀₀(14 ng/mL) (*P < 0.05), significantly decreased LDH (*P < 0.05) and significantly increased SOD (*P < 0.05) activities. However, the NO production, and Gpx, CAT, and Total antioxidant activities were not affected in MCF-7 breast cancer cells. PBMC were not altered by colloidal silver.</p> <p>Conclusions</p> <p>The present results showed that colloidal silver might be a potential alternative agent for human breast cancer therapy.</p

Horsetail (<i>Equisetum hyemale</i>) Extract Accelerates Wound Healing in Diabetic Rats by Modulating IL-10 and MCP-1 Release and Collagen Synthesis

Traditionally, Equisetum hyemale has been used for wound healing. However, its mechanism of action remains to be elucidated. For this purpose, a 40% ethanolic extract of E. hyemale was prepared. Phytochemical screening revealed the presence of minerals, sterols, phenolic acids, flavonols, a lignan, and a phenylpropenoid. The extract reduced the viability of RAW 264.7 cells and skin fibroblasts at all times evaluated. On the third day of treatment, this reduction was 30–40% and 15–40%, respectively. In contrast, the extract increased the proliferation of skin fibroblasts only after 48 h. In addition, the extract increased IL-10 release and inhibited MCP-1 release. However, the extract did not affect both TGF-β1 and TNF-α released by RAW 264.7 cells. The higher release of IL-10 could be related to the up-/downregulation of inflammatory pathways mediated by the extract components associated with their bioactivity. The extract inhibited the growth of Staphylococcus aureus and Escherichia coli. Topical application of the extract accelerated wound healing in diabetic rats by increasing fibroblast collagen synthesis. These results suggest that E. hyemale extract has great potential for use in the treatment of wounds thanks to its phytochemical composition that modulates cytokine secretion, collagen synthesis, and bacterial growth

Phytochemical and Biological Characterization of the Fractions of the Aqueous and Ethanolic Extracts of <i>Parthenium hysterophorus</i>

In this study, the fractions of the aqueous (AE) and ethanolic (EE) crude extracts of Parthenium hysterophorus were evaluated for their phytochemical composition, cytotoxic, and antioxidant activity. The two extracts were subjected to a fractionation by vacuum liquid chromatography, obtaining seven fractions for each extract. These fractions were evaluated for the presence of phenolic compounds by reverse phase high performance liquid chromatography coupled to mass spectrometer (RP-HPLC-MS) analysis. Their cytotoxic activity was tested with a hemolysis assay. The antioxidant activity was evaluated with the Trolox equivalent antioxidant capacity (TEAC), 2,2-diphenyl-1-picrylhydrazyl (DPPH), and hydroxyl radical (–OH) scavenging assays. In addition, the effect of the fractions on the activity of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT), from human erythrocytes, was evaluated. The phytochemical screening by RP-HPLC-MS mainly showed the presence of flavonoids and hydroxycinnamic acids. The hemolysis assay exhibited a low cytotoxic activity by the fractions of the AE, but the fractions of the EE exhibited a hemolytic effect. The fractions of the AE and EE showed significant antioxidant activity to inhibit radicals in the three radical scavenging assays. Moreover, only some fractions of the AE showed a significant increase in the activity of the SOD enzyme, while the activity of CAT exhibited a significant increase by the fractions of the two extracts. The fractions of the AE and EE of P. hysterophorus have phytochemicals with antioxidant activity to inhibit radicals and increase the activity of in vitro antioxidant enzymes

Evaluación biológica in vitro e in silico de derivados de ftalamida como agentes antiproliferativos

Phthalimide is considered a scaffold for the development of new anticancer agents. In this work, the antiproliferative activity of forty-three phthalimide derivatives was evaluated against cervical (HeLa), liver (HepG2), breast (4T1) cancer cell lines, and a normal cell line of murine fibroblasts (3T3). Finally, a molecular docking analysis of phthalimide derivatives on the active site of the enzymes DNA methyltransferase 1 (DNMT1) and vascular endothelial growth factor receptor 2 (VEGR2) as potential drug targets was performed. The compounds, C16, E11, and E16 showed the best antiproliferative activity against the cell lines HeLa and 4T1. Only, the compound H16 decreased 32% cell proliferation against HepG2 cell line. The compounds H5, H16, E2, E16, and C1 did not affect the proliferation of the 3T3 cell line. The molecular docking analysis showed that phthalimide derivatives have a greater affinity for DNMT1 than S-adenosyl-l-homocysteine, a potent DNMT1 inhibitor. However, molecular docking results do not correlate with their antiproliferative effects, suggesting another potential mechanism of action for the active compounds.La estructura de la ftalimida es considerada un bloque de construcción para el desarrollo de nuevos agentes anticancerígenos. En este trabajo, se evaluó la actividad antiproliferativa de cuarenta y tres derivados de ftalimida contra las líneas celulares cancerígenas de cérvix (HeLa), hígado (HepG2), mama (4T1), y la línea celular normal de fibroblastos murinos (3T3). Por último, se realizó un análisis de acoplamiento molecular de los derivados de la ftalimida en el sitio activo de la enzima metiltransferasa 1 de DNA (DNMT1, por sus siglas en inglés) y el receptor del factor de crecimiento endotelial vascular 2 (VEGR2, por sus siglas en inglés) como posibles blancos farmacológicos. Los compuestos C16, E11 y E16 mostraron la mejor actividad antiproliferativa contra las líneas celulares HeLa y 4T1. Solamente, el compuesto H16 disminuyó 32% la proliferación celular de la línea HepG2. Los compuestos H5, H16, E2, E16 y C1 no afectaron la proliferación celular de la línea 3T3. El análisis de acoplamiento molecular demostró que los derivados de la ftalimida tienen una mayor afinidad que la S-adenosil-l-homocisteína, un potente inhibidor de la metiltransferasa 1 de DNA. Sin embargo, los resultados del acoplamiento molecular no se correlacionan con los efectos antiproliferativos; lo cual sugiere que los compuestos activos tienen otro mecanismo de acción