Dataset Information

An in-silico study examining the induction of apoptosis by Cryptotanshinone in metastatic melanoma cell lines.

ABSTRACT:

Background

Metastatic melanoma is an aggressive form of skin cancer that evades various anti-cancer treatments including surgery, radio-,immuno- and chemo-therapy. TRAIL-induced apoptosis is a desirable method to treat melanoma since, unlike other treatments, it does not harm non-cancerous cells. The pro-inflammatory response to melanoma by nF ?B and STAT3 pathways makes the cancer cells resist TRAIL-induced apoptosis. We show that due to to its dual action on DR5, a death receptor for TRAIL and on STAT3, Cryptotanshinone can be used to increase sensitivity to TRAIL.

Methods

The development of chemoresistance and invasive properties in melanoma cells involves several biological pathways. The key components of these pathways are represented as a Boolean network with multiple inputs and multiple outputs.

Results

The possible mutations in genes that can lead to cancer are captured by faults in the combinatorial circuit and the model is used to theoretically predict the effectiveness of Cryptotanshinone for inducing apoptosis in melanoma cell lines. This prediction is experimentally validated by showing that Cryptotanshinone can cause enhanced cell death in A375 melanoma cells.

Conclusion

The results presented in this paper facilitate a better understanding of melanoma drug resistance. Furthermore, this framework can be used to detect additional drug intervention points in the pathway that could amplify the action of Cryptotanshinone.

SUBMITTER: Saraf RS

PROVIDER: S-EPMC6116360 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Publications

An in-silico study examining the induction of apoptosis by Cryptotanshinone in metastatic melanoma cell lines.

Saraf Radhika S RS Datta Aniruddha A Sima Chao C Hua Jianping J Lopes Rosana R Bittner Michael M

BMC cancer 20180829 1

<h4>Background</h4>Metastatic melanoma is an aggressive form of skin cancer that evades various anti-cancer treatments including surgery, radio-,immuno- and chemo-therapy. TRAIL-induced apoptosis is a desirable method to treat melanoma since, unlike other treatments, it does not harm non-cancerous cells. The pro-inflammatory response to melanoma by nF κB and STAT3 pathways makes the cancer cells resist TRAIL-induced apoptosis. We show that due to to its dual action on DR5, a death receptor for T ...[more]

PMID: 30157799

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Project description:Melanoma can progress rapidly from a slow-growing surgically curable lesion to aggressive metastatic disease, with high mortality and poor response to current therapies. The mechanisms underlying melanoma progression and resistance to therapeutic agents are not well understood. There are few treatment options for melanoma once it has metastasized, and new biomarkers that aid diagnosis, predict clinical outcome, and suggest new therapies are required. This aim of this study was to invesigate the molecular basis of melanoma biology and heterogeneity by defining genomic characteristics that correlated with tumour phenotype in a novel panel of 25 cell lines derived largely from New Zealand patients with metastatic melanoma. The goals of this study were to (i) stratify melanoma cell lines by using global gene expression profiling ; (ii) correlate gene expression profiles with invasive potential; and (iii) identify new prognostic markers and therapeutic targets that might aid clinical cancer diagnosis and management. Two-colour spotted oligonucleotide microarrays were used to measure global gene expression in metastatic melanoma cell lines against a common universal reference. Biological replication was achieved by performing replicate arrays on a subset of randomly selected cell lines, in which the replicate total RNA samples were isolated from different vials of cells at different passage numbers, grown by different researchers, and often in different laboratories. Further, NZM01 and NZM02 were derived from different tumours from the same patient at different surgeries, and NZM07.2 and 07.4 were derived from the NZM07 cell line. The array hybridisations were peformed in three batches. Technical replication was achieved by using intra- and inter-batch replicates with different RNA samples from 6/25 of the cell lines: NZM04, 2 x batch 1, 1 x batch 2; NZM22, 2 x batch 1; NZM40, 1 x batch 1, 1 x batch 2; NZM06, 1 x batch 1, 1 x batch 3; NZM09, 1 x batch 1, 1 x batch 2; NZM15, 1 x batch 2, 1 x batch 3.

Dataset Information

An in-silico study examining the induction of apoptosis by Cryptotanshinone in metastatic melanoma cell lines.

Background

Methods

Results

Conclusion

Publications

An in-silico study examining the induction of apoptosis by Cryptotanshinone in metastatic melanoma cell lines.

Similar Datasets

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