Sulforaphane induces cell cycle arrest and apoptosis in acute lymphoblastic leukemia cells
Suppipat K, Park CS, Shen Y, Zhu X, Lacorazza HD
PloS one · 76 citations
How it was studied
- Design
- In vitro/mechanistic study (classified by our AI screen)
- Studied in
- People, plus animal or lab work
- Main outcome
- Clinical events such as disease or death
Who paid for it
- Funding
- Independent funding
- Nonprofit
- Gabrielle's Angel Foundation for Cancer Research
Based on 1 listed funder(s) and full-text disclosure statement.
Publication
- Published
- 2012-12-12 · PLoS One · vol. 7 · issue 12 · p. e51251
- Publisher
- Public Library of Science
- Cited
- 101 citations · more than 99% of similar papers · 9.9× the field average
- Impact
- Top 10% most cited in its field
- References
- 63 works
- Access
- Open access (journal) · CC-BY
- Research areas
- Acute Lymphoblastic Leukemia research · Genomics, phytochemicals, and oxidative stress · T-cell and Retrovirus Studies
- Keywords
- Sulforaphane, Protein kinase B, Cancer research, Apoptosis, PI3K/AKT/mTOR pathway, Medicine, Cell cycle checkpoint, Programmed cell death, Cyclin-dependent kinase 1, Cell cycle, Pharmacology, Cancer, Immunology, Oncology, Internal medicine, Biology, Biochemistry
- MeSH
- cell line, tumor, humans, thiocyanates, isothiocyanates, sulfoxides, cell cycle, apoptosis, precursor cell lymphoblastic leukemia-lymphoma
5 authors
From US
- Koramit SuppipatTexas Children's Hospital
- Chun Shik ParkBaylor College of Medicine
- Ye ShenBaylor College of Medicine
- Xiao Ping ZhuBaylor College of Medicine
- H. Daniel Lacorazza · correspondingBaylor College of Medicine
Abstract
Acute lymphoblastic leukemia (ALL) is the most common hematological cancer in children. Although risk-adaptive therapy, CNS-directed chemotherapy, and supportive care have improved the survival of ALL patients, disease relapse is still the leading cause of cancer-related death in children. Therefore, new drugs are needed as frontline treatments in high-risk disease and as salvage agents in relapsed ALL. In this study, we report that purified sulforaphane, a natural isothiocyanate found in cruciferous vegetables, has anti-leukemic properties in a broad range of ALL cell lines and primary lymphoblasts from pediatric T-ALL and pre-B ALL patients. The treatment of ALL leukemic cells with sulforaphane resulted in dose-dependent apoptosis and G2/M cell cycle arrest, which was associated with the activation of caspases (3, 8, and 9), inactivation of PARP, p53-independent upregulation of p21(CIP1/WAF1), and inhibition of the Cdc2/Cyclin B1 complex. Interestingly, sulforaphane also inhibited the AKT and mTOR survival pathways in most of the tested cell lines by lowering the levels of both total and phosphorylated proteins. Finally, the administration of sulforaphane to the ALL xenograft models resulted in a reduction of tumor burden, particularly following oral administration, suggesting a potential role as an adjunctive agent to improve the therapeutic response in high-risk ALL patients with activated AKT signaling.
Abstract via Europe PMC. Copyright remains with the authors or publisher (CC BY).
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