Treatment of Vemurafenib-Resistant SKMEL-28 Melanoma Cells with Paclitaxel

Thắng, Nguyễn Đình; Phan, Tuan‐Nghia; Kumasaka, Mayuko Y.; Yajima, Ichiro; Kato, Masashi

doi:10.7314/apjcp.2015.16.2.699

Cited by 11 publications

(7 citation statements)

References 40 publications

(49 reference statements)

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“…Growth factor receptors may also cross activate PI3K/Akt separately or in addition to MAPK/Erk activation. Resistance induced in SKMEL28 cells increased expression of EGFR and activated Akt (34). Resistant LM17 cells had increased IGF1R expression as well as increased Akt phosphorylation (35).…”

Section: Introductionmentioning

confidence: 99%

“…However, it has been shown that lower vemurafenib plasma concentration was significantly associated with higher likelihood of tumor progression, and patients had high inter-individual variability in vemurafenib plasma concentration (13.0–109.8 μg/ml) (59). Others have noted that the melanoma cell lines may become dependent on the presence of the BRAF inhibitor for continued growth and continuous treatment is often required, which may potentially be mitigated through a pulsed treatment method (13, 28, 34, 60). Mechanisms regulating development of resistance in each type of model may be different, and clear distinctions should be made between which type of model was employed.…”

Section: Introductionmentioning

confidence: 99%

“…Care must also be taken when reporting drug sensitivity since common colorimetric assays may not be accurate or reproducible due to variations in growth rate; a cell counting based method should be employed when possible (61, 62). Multiple studies have observed changes in cell line growth rate after developing treatment resistance, which may be dependent on the presence of drug (13, 34, 47, 60). Growth rate changes may confound the measurement of drug sensitivity between treatment resistant and pre-treatment cells.…”

Section: Introductionmentioning

confidence: 99%

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Diverse Mechanisms of BRAF Inhibitor Resistance in Melanoma Identified in Clinical and Preclinical Studies

2019

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BRAF inhibitor therapy may provide profound initial tumor regression in metastatic melanoma with BRAF V600 mutations, but treatment resistance often leads to disease progression. A multi-center analysis of BRAF inhibitor resistant patient tissue samples detected genomic changes after disease progression including multiple secondary mutations in the MAPK/Erk signaling pathway, mutant BRAF copy number gains, and BRAF alternative splicing as the predominant putative mechanisms of resistance, but 41.7% of samples had no known resistance drivers. In vitro models of BRAF inhibitor resistance have been developed under a wide variety of experimental conditions to investigate unknown drivers of resistance. Several in vitro models developed genetic alterations observed in patient tissue, but others modulate the response to BRAF inhibitors through increased expression of receptor tyrosine kinases. Both secondary genetic alterations and expression changes in receptor tyrosine kinases may increase activation of MAPK/Erk signaling in the presence of BRAF inhibitors as well as activate PI3K/Akt signaling to support continued growth. Melanoma cells that develop resistance in vitro may have increased dependence on serine or glutamine metabolism and have increased cell motility and metastatic capacity. Future studies of BRAF inhibitor resistance in vitro would benefit from adhering to experimental parameters that reflect development of BRAF inhibitor resistance in patients through using multiple cell lines, fully characterizing the dosing strategy, and reporting the fold change in drug sensitivity.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Diverse Mechanisms of BRAF Inhibitor Resistance in Melanoma Identified in Clinical and Preclinical Studies

2019

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“…Statistical analysis was performed according to methods previously described (Dinh Thang et al, 2015;Nguyen et al, 2015). For toxicity/teratogenicity tests on zebrafish embryos, all statistical analyses, including regressions and comparison tests, were carried out using GraphPad Prism v.5.04 for Windows (GraphPad Software, La Jolla, CA).…”

Section: Discussionmentioning

confidence: 99%

“…The cDNA was then synthesized by reverse transcription of total RNA using Super-scriptTMIII reverse transcriptase, according to a previously published protocol (Dinh Thang et al, 2015;Nguyen et al, 2015). Real-time quantitative RT-PCR with SYBR green was performed using power SYBR1 Green PCR master mix (Applied Biosystems, i.e.…”

Section: Gene Analysismentioning

confidence: 99%

Toxicological and melanin synthesis effects of Polygonum multiflorum root extracts on zebrafish embryos and human melanocytes

Thanh

Thắng

2016

Biomed Res Ther

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Abstract-Introduction: Polygonum multiflorum (PM) has been commonly used as folk medicine for treatment of various conditions, such as early graying of hair in humans. However, there have been limited studies which have evaluated the toxicological and biological effects of PM in vitro as well as in vivo. In this study, PM root extracts in ethyl acetate (PM-E) and in distilled water (PM-W) were examined for their effects on the development of teratogenic defects/deaths. Additionally, they were evaluated for their effects on melanin formation in human melanocytes and pigmentation in embryos/larvae of wild type strain AB zebrafish (Danio rerio). Methods: Phytochemicals in PM roots were extracted in several solvents with increasing in their polarities. Chemical exposure tests were performed to investigate the toxic effects of PM root extracts on Zerbrafish embryos/larvae. Total melanins formed in zebrafish embryos/larvae as well as in human melanocytes were measured by spectrophotometer using dual wavelengths of 415 and 400 nm. Gene expressions were analyzed by realtime PCR. All experiments were independently repeated three times and statistical analyzed. Results: Our results showed that PM root extracts at concentrations of 40 mg/L and 105 mg/L induced the development of teratogenic defects, including yolk sac edema (or heart edema), hemovascular defects, necrosis and abnormal trunk in zebrafish embryos at 4 days post fertilization; teratogenic indexes (TIs) were 1.43 and 0.63 for ethyl acetate extract and distilled water extract, respectively. Our results also demonstrated that PM-W significantly increased the pigmentation level of embryos/larvae and induced melanin formation in human melanocytes. The amount of melanin in PM-W-exposed embryos/larvae was 2.2-fold and 1.71-fold greater than those in the control embryos/larvae and control melanocytes, respectively. Conclusion: Our study also showed that the increased level of pigmentation in PM-W embryos/larvae or melanin biosynthesis in melanocytes were both regulated by activation of tyrosinase. Conclusively, our study suggests that PM root extracts could be used as potential agents for treatment of early hair graying as well as various other diseases related to loss of pigmentation. However, these PM root extracts may also have some negative effects on embryos; therefore it should be careful when using for women during pregnancy.

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Application of the metabolomics approach to the discovery of active compounds from Brazilian trees against resistant human melanoma cells

Kato

Stavis

Boaretto

et al. 2021

Phytochemical Analysis

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Introduction:The chemical diversity of plants plays an essential role in the development of new drugs. However, new bioactive compound identification and isolation are challenging due to the complexity and time-consuming nature of the traditional process. Recently, alternative strategies have become popular, such as the statistical approach to correlate compounds with biological activities, overcoming bottlenecks in bioactive natural product research.Objective: We aimed to determine bioactive compounds against resistant human melanoma cells from leaves of Aspidosperma subincanum, Copaifera langsdorffii, Coussarea hydrangeifolia, Guarea guidonea and Tapirira guianensis, using a metabolomics approach. Material and Methods:The extracts and fractions were obtained by accelerated solvent extraction (ASE) and tested against resistant melanoma cells SK-MEL-28 and SK-MEL-103. Chemical analysis was performed by high-performance diode array detector tandem mass spectrometry (HPLC-DAD-MS/MS). Chemical and biological data were analysed through univariate and multivariate analysis. Results:The species present high chemical diversity, including indole alkaloids, glycosylated flavonoids, galloylquinic acid derivatives, cinnamic acid derivatives, and terpenes. The ASE fractionation separated the compounds according to the physicochemical properties; only C. langsdorffii and T. guianensis extracts were active.Both results from the chemical profile and the biological assay were treated using a metabolomics approach to identify the contribution of different classes of secondary metabolites in the viability of human melanoma cells. The analyses showed the metabolites from C. langsdorffii and T. guianensis, such as polyphenols and terpenes, were the main compounds correlated with the biological response. Conclusion:These findings afford alternative pathways that are trustworthy and less time-consuming to identify new bioactive compounds against multidrug-resistant human melanoma cells.

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Treatment of Vemurafenib-Resistant SKMEL-28 Melanoma Cells with Paclitaxel

Cited by 11 publications

References 40 publications

Diverse Mechanisms of BRAF Inhibitor Resistance in Melanoma Identified in Clinical and Preclinical Studies

Diverse Mechanisms of BRAF Inhibitor Resistance in Melanoma Identified in Clinical and Preclinical Studies

Toxicological and melanin synthesis effects of Polygonum multiflorum root extracts on zebrafish embryos and human melanocytes

Application of the metabolomics approach to the discovery of active compounds from Brazilian trees against resistant human melanoma cells

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