22β-hydroxytingenone induces apoptosis and suppresses invasiveness of melanoma cells by inhibiting MMP-9 activity and MAPK signaling

Aranha, Elenn Suzany Pereira; Portilho, Adrhyann Jullyanne de Sousa; Sousa, Leilane Bentes de; Silva, Emerson Lucena da; Mesquita, Felipe Pantoja; Rocha, Waldireny Caldas; Silva, Felipe M. A. da; Lima, Émerson Silva; Alves, Ana Paula Negreiros Nunes; Koolen, Héctor H. F.; Montenegro, Raquel Carvalho; Vasconcellos, Marne Carvalho de

doi:10.1016/j.jep.2020.113605

Cited by 12 publications

(9 citation statements)

References 58 publications

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“…Acridine orange is a vital dye that stains both living and dead cells, whereas ethidium bromide only stains cells that have lost their membrane integrity. Living cells turn green and can thus be distinguished from apoptotic cells ( Ralph et al, 2016 ; Aranha et al, 2021 ). After treatment with CAP PZ2 for 30 and 60 s, a significant decrease in the viability of HT29 and A549 cells was detected, while the number of apoptotic cells increased after 30 and 60 s of plasma treatment.…”

Section: Resultsmentioning

confidence: 99%

Cold atmospheric plasma induces apoptosis in human colon and lung cancer cells through modulating mitochondrial pathway

Wang

Mang

et al. 2022

Front. Cell Dev. Biol.

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Cold atmospheric plasma (CAP) is an emerging and promising oncotherapy with considerable potential and advantages that traditional treatment modalities lack. The objective of this study was to investigate the effect and mechanism of plasma-inhibited proliferation and plasma-induced apoptosis on human lung cancer and colon cancer cells in vitro and in vivo. Piezobrush® PZ2, a handheld CAP unit based on the piezoelectric direct discharge technology, was used to generate and deliver non-thermal plasma. Firstly, CAPPZ2 treatment inhibited the proliferation of HT29 colorectal cancer cells and A549 lung cancer cells using CCK8 assay, caused morphological changes at the cellular and subcellular levels using transmission electron microscopy, and suppressed both types of tumor cell migration and invasion using the Transwell migration and Matrigel invasion assay. Secondly, we confirmed plasma-induced apoptosis in the HT29 and A549 cells using the AO/EB staining coupled with flow cytometry, and verified the production of apoptosis-related proteins, such as cytochrome c, PARP, cleaved caspase-3 and caspase-9, Bcl-2 and Bax, using western blotting. Finally, the aforementioned in vitro results were tested in vivo using cell-derived xenograft mouse models, and the anticancer effect was confirmed and attributed to CAP-mediated apoptosis. The immunohistochemical analysis revealed that the expression of cleaved caspase-9, caspase-3, PARP and Bax were upregulated whereas that of Bcl-2 downregulated after CAP treatment. These findings collectively suggest that the activation of the mitochondrial pathway is involved during CAPPZ2-induced apoptosis of human colon and lung cancer cells in vitro and in vivo.

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Section: Resultsmentioning

confidence: 99%

Cold atmospheric plasma induces apoptosis in human colon and lung cancer cells through modulating mitochondrial pathway

Wang

Mang

et al. 2022

Front. Cell Dev. Biol.

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“…The MAPK1 gene plays an important role in regulating the differentiation and growth of cells. According to the mechanism of the signaling pathway, as long as there were protein functional problems in the signaling pathway, it will cause serious disease, and this disease was generally related to tumors [ 33 ].…”

Section: Resultsmentioning

confidence: 99%

Correlation Analysis of Gene and Radiomic Features in Colorectal Cancer Liver Metastases

Wang

Guo

et al. 2022

Computational and Mathematical Methods in Medicine

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Colorectal cancer liver metastasis (CRLM) was one of the cancers with high mortality. Clinically, the target point was determined by invasive detection, which increased the suffering of patients and the cost of treatment. If the target point was found through the relationship between early radiomic information and genetic information, it was expected to assist doctors in diagnosing disease, formulating treatment plans, and reducing the pain and burden of patients. In this study, gene coexpression analysis and hub gene mining were first performed on the gene data; secondly, quantitative radiomic features were extracted from CT-enhanced radiomic data to obtain features highly correlated with CRLM; and finally, we analyzed the relationship between gene features and radiomic feature correlations by establishing a link between early radiomic features and gene sequencing and finding highly correlated expressions. This experiment demonstrated that radiomic features could be used to mine gene attributes. Based on the four previously identified genes (NRAS, KRAS, BRAF, and PIK3CA), we identified two novel genes, MAPK1 and STAT1, highly associated with CRLM. There were specific correlations between these 6 genes and radiomic features (shape_elongation, glcm, glszm, firstorder_10percentile, gradient, exponent_firstorder_Range, and gradient_glszm_SmallAreaLowGrayLevel). Therefore, this paper established the correlation between radiomic features and genes, and through radiomic features, we could find the genes associated with them, which was expected to achieve noninvasive prediction of liver metastasis.

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“…Other potential targets revealed during the in silico “target fishing” reverse screening, including Poly(ADP-ribose)polymerase (PARP), 82, 83 phosphodiesterase type 5, 84, 85 orphan nuclear receptor LRH-1, 86, 87 nuclear receptor ROR-gamma, 88, 89 matrix metallopeptidase 9 (MMP9), 90 NAD-dependent deacetylase Sirtuin 2, 91 and cholesterol ester transfer protein, 92 all believed to play important roles in skin carcinogenesis. There is no doubt that the wealth of information gathered here will be useful in further studies towards the optimizing the hit molecules’ activity and determining their putative drug target and potential mechanism(s) of action.…”

Section: Resultsmentioning

confidence: 99%

“…78 It should also be mentioned that PI3K/RAC alpha serine/threonine protein kinase (AKT)/mTOR signaling pathway has been shown to be over-activated in some types of skin cancers, 80 with the anti-proliferative activity of some phenolic compounds against SK-MEL-2 cancer cells attributed to the downregulation of the PI3K/AKT/mTOR signaling pathway, which induces a mitochondrial-dependent apoptosis. 81 Other potential targets revealed during the in silico "target fishing" reverse screening, including Poly(ADPribose)polymerase (PARP), 82,83 phosphodiesterase type 5, 84,85 orphan nuclear receptor LRH-1, 86,87 nuclear receptor ROR-gamma, 88,89 matrix metallopeptidase 9 (MMP9), 90 NAD-dependent deacetylase Sirtuin 2, 91 and cholesterol ester transfer protein, 92 all believed to play important roles in skin carcinogenesis. There is no doubt that the wealth of information gathered here will be useful in further studies towards the optimizing the hit molecules' activity and determining their putative drug target and potential mechanism(s) of action.…”

Section: In Silico Target(s) Prediction Pharmacokinetic and Admet Stu...mentioning

confidence: 99%

Identification of potential inhibitors of cutaneous Melanoma and Non-Melanoma skin cancer cells through in-vitro and in-silico screening of a small library of Phenolic compounds

Boateng

Roy

Agbo

et al. 2022

Preprint

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Melanoma and nonmelanoma skin cancer are the most lethal and commonest forms of skin cancers affecting one fifth of the US population. With the aim of identifying new lead compounds as starting point for attaining cost effective therapies, a small library of about 90 molecules was screened in vitro against A375, SKMEL28, A431, SCC12 skin cancer cell lines. About 35 of them, mainly dihydroquinolines, CC and CN linked biphenyls, and substituted methyl gallate or aniline derivatives, displayed low micromolar range activities, primarily against the A431 and SCC12 squamous carcinoma cell lines, with only a handful of these compounds displaying any activity against the A375 and SKMEL28 melanoma cell lines. Compounds 11 (A431: IC50 = 5.0 lower case Greek muM, SCC12: IC50 = 2.9 lower case Greek muM, SKMEL-28: IC50 = 4.9 lower case Greek muM, A375: IC50 = 6.7 lower case Greek muM) and 13 (A431: IC50 = 5.0 lower case Greek muM, SCC-12: IC50 = 3.3 lower case Greek muM, SKMEL-28: IC50 = 13.8 lower case Greek muM, A375: IC50 = 17.1 lower case Greek muM) were the most active across all these cell lines. Furthermore, many of the hit compounds showed little to no activity against mammalian nontumorigenic immortalized HaCaT cells, with a far better selectivity index than cisplatin (a well-known anticancer agent used as a positive control). Compounds 11 and 13 significantly and dose dependently induced apoptosis of SCC12 and SKMEL28 cells as evidenced by the downregulation of Bcl2 and upregulation of Bax protein expression levels, and by cleaved caspase 3, caspase 9 and PARP levels. Both agents also significantly reduced scratch wound healing, colony formation, and activated expression levels of major cancer molecular targets such as RSK/AKT/ERK1/2 and S6K1. To provide a better attribute profile for each of the hit molecules, in silico target(s) prediction, pharmacokinetic and ADMET studies are also reported, together with some preliminary structure activity relationship outlines. The SwissTargetPrediction web-based tool identified CDK8, CLK4, nuclear receptor ROR, tyrosine protein-kinase Fyn/LCK, ROCK1/2, and PARP, all of which are dysregulated in skin cancers, as likely targets for these hit compounds. Furthermore, the SwissADME web_tool predicted these compounds to exhibit high GI tract absorption, good skin permeation, and a viable biodegradability profile. To summarize, these data highlight the promising anticancer potential of these small molecules leads, warranting further investigation and/or optimization towards obtaining clinical candidates for combatting both melanoma and nonmelanoma skin cancers.

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22β-hydroxytingenone induces apoptosis and suppresses invasiveness of melanoma cells by inhibiting MMP-9 activity and MAPK signaling

Cited by 12 publications

References 58 publications

Cold atmospheric plasma induces apoptosis in human colon and lung cancer cells through modulating mitochondrial pathway

Cold atmospheric plasma induces apoptosis in human colon and lung cancer cells through modulating mitochondrial pathway

Correlation Analysis of Gene and Radiomic Features in Colorectal Cancer Liver Metastases

Identification of potential inhibitors of cutaneous Melanoma and Non-Melanoma skin cancer cells through in-vitro and in-silico screening of a small library of Phenolic compounds

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