Dataset Information

Curcumin-Induced Global Profiling of Transcriptomes in Small Cell Lung Cancer Cells.

ABSTRACT:

Background

Curcumin, one of the promising candidates for supplementary therapy in cancer treatment, has been demonstrated by numerous preclinical and clinical evidence to be beneficial in treating various cancers. Apart from the critical role in a deluge of pathological processes, some mRNAs, in particular, microRNAs (miRNAs), are also involved in the anti-tumor activity. Therefore, our research focused on the possible effects of curcumin on small cell lung cancer (SCLC) cells and drew a comprehensive transcriptomes profile by high throughput sequencing to understand the molecular mechanism of curcumin as an anti-tumor agent.

Methods

First, we calculated the apoptosis rate of H446 cells (a human SCLC cell line) cultured with curcumin. The high output sequencing uncovered the altered expression profile of genes and miRNAs. KEGG analysis selected the potential signal pathway associated with the antiproliferative property of curcumin. Finally, miRNAs significantly changed, as well as the regulatory roles of those miRNAs in cell apoptosis were determined.

Result

The apoptosis rate of H446 cells increased under the elevated concentration of curcumin treatment. And cell cycle-related genes downregulated in the curcumin-treated cells. Besides, miRNA-548ah-5p of a high level acted as a negative role in the anticarcinogenic activity of curcumin.

Conclusion

Our findings not only enriched the understanding of anti-tumor activity initiated by curcumin through figuring out the downregulated cell cycle-related pathways but also shed light on its novel therapeutic application.

SUBMITTER: Mo F

PROVIDER: S-EPMC7835540 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Publications

Curcumin-Induced Global Profiling of Transcriptomes in Small Cell Lung Cancer Cells.

Mo Fei F Xiao Yinan Y Zeng Hao H Fan Dian D Song Jinen J Liu Xiaobei X Luo Meng M Ma Xuelei X

Frontiers in cell and developmental biology 20210112

<h4>Background</h4>Curcumin, one of the promising candidates for supplementary therapy in cancer treatment, has been demonstrated by numerous preclinical and clinical evidence to be beneficial in treating various cancers. Apart from the critical role in a deluge of pathological processes, some mRNAs, in particular, microRNAs (miRNAs), are also involved in the anti-tumor activity. Therefore, our research focused on the possible effects of curcumin on small cell lung cancer (SCLC) cells and drew a ...[more]

PMID: 33511113

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Project description:BackgroundEpidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are being wildly used as target therapy in non-small-cell lung cancer (NSCLC). However, NSCLC patients with wild-type EGFR and KRAS mutation are primary resistant to EGFR-TKIs such as gefitinib. Curcumin has been known as a potential therapeutic agent for several major human cancers. In this study, we investigated the effect of curcumin on the reversal of gefitinib resistance in NSCLC cells as well as their molecular bases.MethodsH157 (wild-type EGFR and KARS mutation) and H1299 (wild-type EGFR and HRAS mutation) cells were treated with gefitinib or curcumin alone, or the two combination, and then cell viability, EGFR activity, expressions of Sp1 and Sp1-dependent proteins and receptor tyrosine kinases, markers of autophagy and apoptosis were examined by using CCK-8, colony formation, immunoblot, quantitative PCR, immunofluoscence, and flow cytometry assays. Also xenograft experiments were conduced to test the synergism of curcumin to gefitinib.ResultsOur results showed that curcumin significantly enhanced inhibitory effect of gefitinib on primary gefitinib-resistant NSCLC cell lines H157 and H1299. Combination treatment with curcumin and gefitinib markedly downregulated EGFR activity through suppressing Sp1 and blocking interaction of Sp1 and HADC1, and markedly suppressed receptor tyrosine kinases as well as ERK/MEK and AKT/S6K pathways in the resistant NSCLC cells. Meanwhile, combination treatment of curcumin and gefitinib caused dramatic autophagy induction, autophagic cell death and autophagy-mediated apoptosis, compared to curcumin or gefitinib treatment alone, as evidenced by the findings that curcumin and gefitinib combination treatment-produced synergistic growth inhibition and apoptosis activation can be reversed by pharmacological autophagy inhibitors (Baf A1 or 3-MA) or knockdown of Beclin-1 or ATG7, also can be partially returned by pan-caspase inhibitor (Z-VAD-FMK) in H157 and H1299 cells. Xenograft experiments in vivo yielded similar results.ConclusionsThese data indicate that the synergism of curcumin on gefitinib was autophagy dependent. Curcumin can be used as a sensitizer to enhance the efficacy of EGFR-TKIs and overcome the EGFR-TKI resistance in NSCLC patients with wild-type EGFR and/or KRAS mutation.

Project description:Molecular profiling of NSCLC is essential for optimising treatment decisions, but often incomplete. We assessed the efficacy of protocolised molecular profiling in the current standard-of-care (SoC) in a prospective observational study in the Netherlands and measured the effect of providing standardised diagnostic procedures. We also explored the potential of plasma-based molecular profiling in the primary diagnostic setting. This multi-centre prospective study was designed to explore the performance of current clinical practice during the run-in phase using local SoC tissue profiling procedures. The subsequent phase was designed to investigate the extent to which comprehensive molecular profiling (CMP) can be maximized by protocolising tumour profiling. Successful molecular profiling was defined as completion of at least EGFR and ALK testing. Additionally, PD-L1 tumour proportions scores were explored. Lastly, the additional value of centralised plasma-based testing for EGFR and KRAS mutations using droplet digital PCR was evaluated. Total accrual was 878 patients, 22.0% had squamous cell carcinoma and 78.0% had non-squamous NSCLC. Stage I-III was seen in 54.0%, stage IV in 46.0%. Profiling of EGFR and ALK was performed in 69.9% of 136 patients included in the run-in phase, significantly more than real-world data estimates of 55% (p<0.001). Protocolised molecular profiling increased the rate to 77.0% (p = 0.049). EGFR and ALK profiling rates increased from 77.9% to 82.1% in non-squamous NSCLC and from 43.8% to 57.5% in squamous NSCLC. Plasma-based testing was feasible in 98.4% and identified oncogenic driver mutations in 7.1% of patients for whom tissue profiling was unfeasible. This study shows a high success rate of tissue-based molecular profiling that was significantly improved by a protocolised approach. Tissue-based profiling remains unfeasible for a substantial proportion of patients. Combined analysis of tumour tissue and circulating tumour DNA is a promising approach to allow adequate molecular profiling of more patients.

Dataset Information

Curcumin-Induced Global Profiling of Transcriptomes in Small Cell Lung Cancer Cells.

Background

Methods

Result

Conclusion

Publications

Curcumin-Induced Global Profiling of Transcriptomes in Small Cell Lung Cancer Cells.

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