Autophagy inhibition enhances sulforaphane-induced apoptosis in human breast cancer cells
Kanematsu S, Uehara N, Miki H, Yoshizawa K, Kawanaka A, Yuri T, Tsubura A
Anticancer research · 119 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
- Funding not disclosed
Publication
- Published
- 2010-09-01 · Anticancer Res · vol. 30 · issue 9 · pp. 3381–90
- Publisher
- National Institutes of Health
- Cited
- 147 citations · more than 96% of similar papers · 4.5× the field average
- Impact
- Top 10% most cited in its field
- References
- 41 works
- Access
- Paywalled
- Research areas
- Genomics, phytochemicals, and oxidative stress · Curcumin's Biomedical Applications · Autophagy in Disease and Therapy
- Keywords
- Autophagy, Apoptosis, Viability assay, Programmed cell death, Cell cycle, Trypan blue, Cancer cell, Biology, Flow cytometry, Cyclin B1, Molecular biology, Cell growth, MTT assay, Cancer research, Cell biology, Chemistry, Cyclin-dependent kinase 1, Cancer, Biochemistry
- MeSH
- cell line, tumor, humans, breast neoplasms, thiocyanates, isothiocyanates, sulfoxides, anticarcinogenic agents, enzyme inhibitors, microscopy, electron, transmission, fluorescent antibody technique, blotting, western, flow cytometry, cell separation, signal transduction, apoptosis, cell proliferation, autophagy, female
7 authors
From JP
- Sayaka KanematsuKansai Medical University
- Norihisa UeharaKansai Medical University
- Hisanori MikiKansai Medical University
- Katsuhiko YoshizawaKansai Medical University
- Ayako KawanakaKansai Medical University
- Takashi YuriKansai Medical University
Abstract
Aim
Sulforaphane (SFN), which is present in cruciferous vegetables, induces growth arrest and/or cell death in cancer of various organs. The involvement of autophagy in the SFN-induced apoptotic death of human breast cancer cells was investigated.
Materials and methods
Cell proliferation and viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and trypan blue exclusion assay. Flow cytometry, immunofluorescence, electron microscopy, and Western blot analysis were used for detection of apoptosis and autophagy, and the role of autophagy was assessed using autophagy inhibitors.
Results
SFN dose- and time-dependently retarded the growth and induced cell death in MCF-7 and MDA-MB-231 human breast cancer cells. In MDA-MB-231 cells, 30 μM SFN caused S and G2/M cell-cycle arrest associated with increased p21WAF1 and p27KIP1 levels and decreased cyclin A, cyclin B1 and CDC2 levels. Cell death was due to apoptosis with increased caspase-3 and lowered BCL-2 levels. In addition, the SFN-treated cells exhibited autophagy, as characterized by the appearance of autophagic vacuoles by electron microscopy, the accumulation of acidic vesicular organelles by flow cytometry, and the punctuate patterns of microtubule-associated protein 1 light chain 3 (LC3) by fluorescein microscopy. The levels of LC3-I and -II proteins (processed forms of LC3-I) and LC3 mRNA were increased. Treatment with autophagy inhibitor bafilomycin A1 (but not 3-methyladenine) with SFN significantly enhanced apoptosis, which was accompanied by increases in the level of BAX and the cleavage of caspase-3 and poly(ADP-ribose)polymerase (PARP)-1 and decreases in the mitochondrial membrane potential (ΔΨm).
Conclusion
These results indicate a cytoprotective role of autophagy against SFN-induced apoptosis and that the combination of SFN treatment with autophagy inhibition may be a promising strategy for breast cancer control.
Abstract via Europe PMC. Copyright remains with the authors or publisher.
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