Sulforaphane metabolites reduce resistance to paclitaxel via microtubule disruption
Wang Y, Zhou Y, Zheng Z, Li J, Yan Y, Wu W
Cell death & disease · 38 citations
Review labels
Neutral facts our review recorded about how this study was done. They describe method, never whether we like the result.
How it was studied
- Design
- In vitro/mechanistic study (classified by our AI screen)
- Studied in
- Cells or lab samples
- Main outcome
- Mechanisms only
Who paid for it
- Funding
- Independent funding
- Government
- National Natural Science Foundation of China
- Grants
- National Natural Science Foundation of China (81601993); National Natural Science Foundation of China (81272843); National Natural Science Foundation of China (81272843 and 81601993); National Natural Science Foundation of China (81901993)
Based on 1 listed funder(s) and full-text disclosure statement.
Publication
- Published
- 2018-11-14 · Cell Death Dis · vol. 9 · issue 11 · p. 1134
- Publisher
- Springer Nature
- Cited
- 56 citations · more than 89% of similar papers · 2.2× the field average
- References
- 51 works
- Access
- Open access (journal) · CC-BY
- Research areas
- Genomics, phytochemicals, and oxidative stress · Histone Deacetylase Inhibitors Research · Synthesis and biological activity
- Keywords
- Sulforaphane, Paclitaxel, XIAP, Downregulation and upregulation, Apoptosis, Tubulin, Chemistry, Cancer research, Microtubule, Biology, Caspase, Programmed cell death, Cell biology, Cancer, Biochemistry
- MeSH
- microtubules, humans, carcinoma, non-small-cell lung, lung neoplasms, paclitaxel, isothiocyanates, sulfoxides, proteasome endopeptidase complex, tubulin, mitogen-activated protein kinase 1, mitogen-activated protein kinase 3, rna, small interfering, antineoplastic agents, drug combinations, signal transduction, apoptosis, cell proliferation, gene expression regulation, neoplastic, drug resistance, neoplasm, aged, middle aged, female, male, hsp70 heat-shock proteins, neoplasm grading, a549 cells
6 authors
From CN
- Yalin WangCapital Medical University
- Yan ZhouCapital Medical University
- Zhongnan ZhengCapital Medical University
- Juntao LiCapital Medical University
- Yu‐Ting YanCapital Medical University
- Wei Wu · correspondingCapital Medical University; Chinese Institute for Brain Research; Beijing Institute for Brain Disorders
Abstract
Long treatment with paclitaxel (PTX) might increase resistance and side-effects causing a failure in cancer chemotherapy. Here we uncovered that either sulforaphane-cysteine (SFN-Cys) or sulforaphane-N-acetyl-cysteine (SFN-NAC) induced apoptosis via phosphorylated ERK1/2-mediated upregulation of 26 S proteasome and Hsp70, and downregulation of βIII-tubulin, XIAP, Tau, Stathmin1 and α-tubulin causing microtubule disruption in human PTX-resistant non-small cell lung cancer (NSCLC) cells. Knockdown of either βIII-tubulin or α-tubulin via siRNA increased cell sensitivity to PTX, indicating that these two proteins help cells increase the resistance. Tissue microarray analysis showed that overexpression of βIII-tubulin correlated to NSCLC malignant grading. Immunofluorescence staining also showed that SFN metabolites induced a nest-like microtubule protein distribution with aggregation and disruption. Co-immunoprecipitation showed that SFN metabolites reduced the interaction between βIII-tubulin and Tau, and that between α-tubulin and XIAP. The combination of PTX with SFN metabolites decreased the resistance to PTX, and doses of both PTX and SFN metabolites, and enhanced apoptosis resulting from activated Caspase-3-caused microtubule degradation. Importantly, the effective dose of SFN metabolites combined with 20 nM PTX will be low to 4 μM. Thus, we might combine SFN metabolites with PTX for preclinical trial. Normally, more than 20 μM SFN metabolites only leading to apoptosis for SFN metabolites hindered their applications. These findings will help us develop a low-resistance and high-efficiency chemotherapy via PTX/SFN metabolites combination.
Abstract via Europe PMC. Copyright remains with the authors or publisher (CC BY).
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