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Phenethyl Isothiocyanate (PEITC) from Cruciferous Vegetables Targets Human Cancer Stem‐Like Cells
Author(s) -
Upadhyaya Bijaya,
Liu Yi,
Wang Dan,
Knudsen David,
Dey Moul
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.130.3
Subject(s) - phenethyl isothiocyanate , cancer research , apoptosis , cd44 , cancer , metastasis , hela , carcinogenesis , cancer cell , sulforaphane , medicine , chemistry , biology , immunology , cell , biochemistry
Scope Cancer stem cells (CSC) are perceived as a key player in cancer chemo‐and‐radio‐therapy resistance, cancer recurrence, and metastasis. PEITC, a dietary bioactive compound, is pro‐apoptotic in various cancer cell lines and primary tumors but its effect on CSC is less known. Our objective was to examine the effects of PEITC on promoting apoptosis in human cervical HeLa CSC (hCSC) in vitro and on attenuation of tumorigenicity in hCSC‐transplanted mice.
Methods and Results PEITC attenuated proliferation of sphere‐culture‐enriched (ANOVA, p 蠄 0.001), aldehyde dehydrogenase (ALDH1) bright , CD44 high⁄+ /CD24 low⁄– , Hoechst 33342‐excluded hCSC in a concentration‐ and time‐dependent manner. PEITC up‐regulated cleaved poly (ADP‐ribose) polymerase ( p 蠄 0.05) and induced death receptors, DR4 ( p 蠄 0.01) and DR5 ( p 蠄 0.001), of tumor necrotic factor‐related apoptosis‐inducing ligand signaling. In NOD/SCID mice, hCSC induced greater tumorogenicity, elevated serum human‐vascular endothelial growth factor A (ELISA), and lung metastasis (H&E staining) compared to HeLa cells, which were attenuated in 10 µM PEITC‐pretreated hCSC group. Ongoing experiments indicate that PEITC down‐regulates ALDH1 ( p 蠄 0.01) (flow cytometry) and specificity protein 1 (immunoblotting), a transcription factor regulating activity of several multi‐drug resistance genes.
Conclusion and Significance PEITC attenuates cell proliferation and tumorigenicity by promoting apoptosis in CSC. This presents a novel opportunity for a dietary approach for preventing cancer recurrence and improving therapeutic outcomes in patients. Research Support‐ NIH (R00AT4245) and SD‐AES (3AH360)