scholarly journals In Vitro Anticancer Potential of Jasione montana and Its Main Components Against Human Amelanotic Melanoma Cells

2021 ◽  
Vol 22 (7) ◽  
pp. 3345
Author(s):  
Aleksandra Maria Juszczak ◽  
Robert Czarnomysy ◽  
Jakub Władysław Strawa ◽  
Marijana Zovko Končić ◽  
Krzysztof Bielawski ◽  
...  
Keyword(s):  
Cell Line ◽  
Melanoma Cell ◽  
Melanoma Cell Line ◽  
Binding Assay ◽  
Annexin V ◽  
Melanoma Cells ◽  
Amelanotic Melanoma ◽  
Cytotoxic Activities ◽  
Ionization Mass ◽  
Caspase 9

Jasione montana L. (Campanulaceae) is used in traditional Belarusian herbal medicine for sleep disorders in children, but the chemical composition and biological activity have not been investigated. In this study, the activities of J. montana extracts, their fractions and main compounds were evaluated in amelanotic melanoma C32 (CRL-1585) cells and normal fibroblasts (PCS-201-012). The extracts and fractions were analyzed using liquid chromatography–photodiode array detection–electrospray ionization–mass spectrometry (LC–PDA–ESI–MS/TOF) to characterize 25 compounds. Further, three major and known constituents, luteolin (22) and its derivatives such as 7-O-glucoside (12) and 7-O-sambubioside (9) were isolated and identified. The cytotoxic activities against fibroblasts and the amelanotic melanoma cell line were determined using the fixable viability stain (FVS) assay. The influence of diethyl ether (Et2O) fraction (JM4) and 22 on apoptosis induction was investigated using an annexin V binding assay. The obtained results showed significant cytotoxicity of JM4 and 22 with IC50 values of 119.7 ± 3.2 and 95.1 ± 7.2 μg/mL, respectively. The proapoptotic potential after 22 treatment in the C32 human amelanotic melanoma cell line was comparable to that of vinblastine sulfate (VLB), detecting 29.2 ± 3.0% apoptotic cells. Moreover, 22 displayed less necrotic potential against melanoma cells than VLB. In addition, the influences of JM4 and 22 on the dysfunction of the mitochondrial membrane potential (MMP), cell cycle and activity of caspases 3, 8, 9, and 10 were established. The effects of JM4 on MMP change (74.5 ± 3.0% of the cells showed a reduced MMP) corresponded to the results obtained from the annexin V binding assay and activation of caspase-9. JM4 and 22 displayed a significant impact on caspase-9 (40.9 ± 2.4% of the cells contained active caspase-9 after JM4 treatment and 16.6 ± 0.8% after incubation with 22) and the intrinsic (mitochondrial) apoptotic pathway. Moreover, studies have shown that JM4 and 22 affect the activation of external apoptosis pathways by inducing the caspase-8 and caspase-10 cascades. Thus, activation of caspase-3 and DNA damage via external and internal apoptotic pathways were observed after treatment with JM4 and 22. The obtained results suggest that J. montana extracts could be developed as new topical preparations with potential anticancer properties due to their promising cytotoxic and proapoptotic potential.

scholarly journals Imidazo[1,2-a]quinoxalines Derivatives Grafted with Amino Acids: Synthesis and Evaluation on A375 Melanoma Cells

Molecules ◽  
2018 ◽  
Vol 23 (11) ◽  
pp. 2987 ◽  
Author(s):  
Adrien Chouchou ◽  
Cindy Patinote ◽  
Pierre Cuq ◽  
Pierre-Antoine Bonnet ◽  
Carine Deleuze-Masquéfa
Keyword(s):  
Amino Acids ◽  
Cell Line ◽  
Melanoma Cell ◽  
Melanoma Cell Line ◽  
First Generation ◽  
Second Generation ◽  
Intrinsic Activity ◽  
Cytotoxic Activities ◽  
A375 Melanoma Cell Line ◽  
A375 Melanoma

Imiqualines (imidazoquinoxaline derivatives) are anticancer compounds with high cytotoxic activities on melanoma cell lines. The first generation of imiqualines, with two lead compounds (EAPB0203 and EAPB0503), shows remarkable in vitro (IC50 = 1 570 nM and IC50 = 200 nM, respectively, on the A375 melanoma cell line) and in vivo activity on melanoma xenografts. The second generation derivatives, EAPB02302 and EAPB02303, are more active, with IC50 = 60 nM and IC50 = 10 nM, respectively, on A375 melanoma cell line. The aim of this study was to optimize the bioavailability of imiqualine derivatives, without losing their intrinsic activity. For that, we achieved chemical modulation on the second generation of imiqualines by conjugating amino acids on position 4. A new series of twenty-five compounds was efficiently synthesized by using microwave assistance and tested for its activity on the A375 cell line. In the new series, compounds 11a, 9d and 11b show cytotoxic activities less than second generation compounds, but similar to that of the first generation ones (IC50 = 403 nM, IC50 = 128 nM and IC50 = 584 nM, respectively). The presence of an amino acid leads to significant enhancement of the water solubility for improved drugability.

scholarly journals IFN-gamma-induced PD-L1 expression in melanoma depends on p53 expression

2019 ◽  
Vol 38 (1) ◽  
Author(s):  
Alexander Thiem ◽  
Sonja Hesbacher ◽  
Hermann Kneitz ◽  
Teresa di Primio ◽  
Markus V. Heppt ◽  
...  
Keyword(s):  
Cell Line ◽  
Melanoma Cell ◽  
Immune Checkpoint ◽  
Melanoma Cell Line ◽  
Protein Gene ◽  
P53 Protein ◽  
Ectopic Expression ◽  
Melanoma Cells ◽  
P53 Expression ◽  
L1 Protein

Abstract Background Immune checkpoint inhibition and in particular anti-PD-1 immunotherapy have revolutionized the treatment of advanced melanoma. In this regard, higher tumoral PD-L1 protein (gene name: CD274) expression is associated with better clinical response and increased survival to anti-PD-1 therapy. Moreover, there is increasing evidence that tumor suppressor proteins are involved in immune regulation and are capable of modulating the expression of immune checkpoint proteins. Here, we determined the role of p53 protein (gene name: TP53) in the regulation of PD-L1 expression in melanoma. Methods We analyzed publicly available mRNA and protein expression data from the cancer genome/proteome atlas and performed immunohistochemistry on tumors with known TP53 status. Constitutive and IFN-ɣ-induced PD-L1 expression upon p53 knockdown in wildtype, TP53-mutated or JAK2-overexpressing melanoma cells or in cells, in which p53 was rendered transcriptionally inactive by CRISPR/Cas9, was determined by immunoblot or flow cytometry. Similarly, PD-L1 expression was investigated after overexpression of a transcriptionally-impaired p53 (L22Q, W23S) in TP53-wt or a TP53-knockout melanoma cell line. Immunoblot was applied to analyze the IFN-ɣ signaling pathway. Results For TP53-mutated tumors, an increased CD274 mRNA expression and a higher frequency of PD-L1 positivity was observed. Interestingly, positive correlations of IFNG mRNA and PD-L1 protein in both TP53-wt and -mutated samples and of p53 and PD-L1 protein suggest a non-transcriptional mode of action of p53. Indeed, cell line experiments revealed a diminished IFN-ɣ-induced PD-L1 expression upon p53 knockdown in both wildtype and TP53-mutated melanoma cells, which was not the case when p53 wildtype protein was rendered transcriptionally inactive or by ectopic expression of p53L22Q,W23S, a transcriptionally-impaired variant, in TP53-wt cells. Accordingly, expression of p53L22Q,W23S in a TP53-knockout melanoma cell line boosted IFN-ɣ-induced PD-L1 expression. The impaired PD-L1-inducibility after p53 knockdown was associated with a reduced JAK2 expression in the cells and was almost abrogated by JAK2 overexpression. Conclusions While having only a small impact on basal PD-L1 expression, both wildtype and mutated p53 play an important positive role for IFN-ɣ-induced PD-L1 expression in melanoma cells by supporting JAK2 expression. Future studies should address, whether p53 expression levels might influence response to anti-PD-1 immunotherapy.

scholarly journals Knocking out the Vitamin D Receptor Enhances Malignancy and Decreases Responsiveness to Vitamin D3 Hydroxyderivatives in Human Melanoma Cells

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3111
Author(s):  
Ewa Podgorska ◽  
Tae-Kang Kim ◽  
Zorica Janjetovic ◽  
Krystyna Urbanska ◽  
Robert C. Tuckey ◽  
...  
Keyword(s):  
Vitamin D ◽  
Cell Line ◽  
Vitamin D Receptor ◽  
Melanoma Cell ◽  
Vitamin D3 ◽  
Melanoma Cell Line ◽  
Inverse Correlation ◽  
Melanoma Cells ◽  
Human Melanoma ◽  
Melanoma Tumor

Vitamin D3 is not only involved in calcium and phosphate metabolism in humans, but it can also affect proliferation and differentiation of normal and cancer cells, including melanoma. The mechanism of the anti-cancer action of vitamin D3 is not fully understood. The nuclear vitamin D receptor (VDR) is crucial for the phenotypic effects of vitamin D hydroxyderivatives. VDR expression shows an inverse correlation with melanoma progression and poor outcome of the disease. In this study we knocked out the VDR in a human melanoma cell line using CRISPR methodology. This enhanced the proliferation of melanoma cells grown in monolayer culture, spheroids or colonies and their migration. Activated forms of vitamin D, including classical 1,25(OH)2D3, 20(OH)D3 and 1,20(OH)2D3, inhibited cell proliferation, migration rate and the ability to form colonies and spheroids in the wild-type melanoma cell line, while VDR KO cells showed a degree of resistance to their action. These results indicate that expression of VDR is important for the inhibition of melanoma growth induced by activated forms of vitamin D. In conclusion, based on our previous clinicopathological analyses and the current study, we suggest that the VDR can function as a melanoma tumor suppressor gene.

Insight into Mechanistic Action of Thymoquinone Induced Melanogenesis in Cultured Melanocytes

2019 ◽  
Vol 26 (12) ◽  
pp. 910-918
Author(s):  
Kamal U. Zaidi ◽  
Firoz N. Khan ◽  
Sharique A. Ali ◽  
Kausar P. Khan
Keyword(s):  
Western Blot ◽  
Signaling Pathways ◽  
Cell Line ◽  
Melanoma Cell ◽  
Melanoma Cell Line ◽  
Protein Kinase Inhibitors ◽  
Tyrosinase Activity ◽  
Dependent Manner ◽  
B16f10 Melanoma ◽  
B16f10 Melanoma Cell

Background: Melanin plays a crucial role in camouflage, social communication and protection against harmful ultraviolet radiations. Melanin is synthesized by melanocytes through melanogenesis and several intrinsic and extrinsic factors are involved during the process. Any change occuring in the normal melanogenesis process can cause severe pigmentation problems of hypopigmentation or hyperpigmentation. Objective: The present study is based on the evaluation of the effect of thymoquinone on melanogenesis and their possible mechanism of action using the B16F10 melanoma cell line for the production via blocking signaling pathways. Methods: Phase contrast microscopy, cell viability, tyrosinase activity, melanin content and western blot analysis were used in the present study. Results: In the present investigation, cultured melanocytes exhibit that the stimulation of melanin synthesis when treated with thymoquinone. Tyrosinase activity and melanin production in B16F10 melanoma cell line was increased in doze-dependent manner. In western blot, we investigated the involvement of the cAMP/PKA pathway in thymoquinone induced melanogenesis. It was observed protein kinase inhibitors PKA, PKC, PKB and MEK1 decreased the stimulatory effects of thymoquinone from 11.45- fold value to 8.312, 6.631, 4.51, and 7.211-fold value, respectively. However, the results also prove that thymoquinone may partially induce tyrosinase expression via PKA, PKB, PKC and MEK1 signaling pathways. Conclusion: The present finding proposed that thymoquinone is a protective challenger for melanogenesis and it might be useful for the treatment of hypopigmentary disorders.

scholarly journals Combined p14ARF and Interferon-β Gene Transfer to the Human Melanoma Cell Line SK-MEL-147 Promotes Oncolysis and Immune Activation

2020 ◽  
Vol 11 ◽  
Author(s):  
Otto Luiz Dutra Cerqueira ◽  
Maria Alejandra Clavijo-Salomon ◽  
Elaine Cristina Cardoso ◽  
Tharcisio Citrangulo Tortelli Junior ◽  
Samir Andrade Mendonça ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Cell Line ◽  
Melanoma Cell ◽  
Immune Activation ◽  
Melanoma Cell Line ◽  
Human Melanoma ◽  
Human Melanoma Cell Line ◽  
Human Melanoma Cell ◽  
Interferon Β

scholarly journals MIF inhibition reverts the gene expression profile of human melanoma cell line-induced MDSCs to normal monocytes

Genomics Data ◽  
2016 ◽  
Vol 7 ◽  
pp. 240-242 ◽  
Author(s):  
Sabine Waigel ◽  
Beatriz E. Rendon ◽  
Gwyneth Lamont ◽  
Jamaal Richie ◽  
Robert A. Mitchell ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Line ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Melanoma Cell ◽  
Melanoma Cell Line ◽  
Human Melanoma ◽  
Human Melanoma Cell Line ◽  
Human Melanoma Cell

CELL KINETIC STUDIES OF THE EFFECT OF VARIOUS KINDS OF CHEMOTHERAPEUTIC AGENTS ON A HUMAN MELANOMA CELL LINE (SEKI, II)

1982 ◽  
Vol 9 (4) ◽  
pp. 271-278 ◽  
Author(s):  
Shinji Shimada ◽  
Makoto Kawashima ◽  
Shinichi Watanabe ◽  
Kiyoshi Yamada ◽  
Masako Mizoguchi ◽  
...  
Keyword(s):  
Cell Line ◽  
Melanoma Cell ◽  
Melanoma Cell Line ◽  
Kinetic Studies ◽  
Chemotherapeutic Agents ◽  
Human Melanoma ◽  
Human Melanoma Cell Line ◽  
Human Melanoma Cell ◽  
Cell Kinetic
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