Phenethyl isothiocyanate hampers growth and progression of HER2-positive breast and ovarian carcinoma by targeting their stem cell compartment.
Animals
Breast Neoplasms
/ metabolism
Cell Line, Tumor
Cell Proliferation
/ drug effects
Female
Humans
Isothiocyanates
/ pharmacology
Mice, Transgenic
Neoplasm Proteins
/ metabolism
Neoplastic Stem Cells
/ drug effects
Ovarian Neoplasms
/ metabolism
Receptor, ErbB-2
/ metabolism
Signal Transduction
/ drug effects
Trastuzumab
/ pharmacology
Breast cancer
Cancer stem cells
HER2
Phenethyl isothiocyanate
Trastuzumab
d16HER2 isoform
Journal
Cellular oncology (Dordrecht)
ISSN: 2211-3436
Titre abrégé: Cell Oncol (Dordr)
Pays: Netherlands
ID NLM: 101552938
Informations de publication
Date de publication:
Dec 2019
Dec 2019
Historique:
accepted:
11
07
2019
pubmed:
4
8
2019
medline:
9
4
2020
entrez:
4
8
2019
Statut:
ppublish
Résumé
Isothiocyanates elicit anticancer effects by targeting cancer stem cells (CSCs). Here, we tested the antitumor activity of phenethyl-isothiocyanate (PEITC), either alone or in combination with trastuzumab, in HER2-positive tumor models. We assessed the in vitro anticancer activity of PEITC, alone or combined with trastuzumab, in HER2-positive BT474, SKBR3, HCC1954 and SKOV3 cancer cells by measuring their sphere forming efficiency (SFE). The expression of the human/rodent CSC biomarkers aldehyde-dehydrogenase (ALDH) and CD29 We found that PEITC significantly impaired the SFE of HER2-positive human cancer cells by decreasing their ALDH-positive compartments. The anti-CSC activity of PEITC was demonstrated by a reduced expression/activation of established cancer-stemness biomarkers. Similar results were obtained with MI6 cells, where PEITC, alone or in combination with trastuzumab, significantly inhibited their SFE. We also found that PEITC hampered the in vivo growth of MI6 nodules by inducing hemorrhagic and necrotic intra-tumor areas and, in combination with trastuzumab, by significantly reducing spontaneous tumor development in d16HER2 transgenic mice. Our results indicate that PEITC targets HER2-positive CSCs and that its combination with trastuzumab may pave the way for a novel therapeutic strategy for HER2-positive tumors.
Identifiants
pubmed: 31376137
doi: 10.1007/s13402-019-00464-w
pii: 10.1007/s13402-019-00464-w
doi:
Substances chimiques
Isothiocyanates
0
Neoplasm Proteins
0
phenethyl isothiocyanate
6U7TFK75KV
Receptor, ErbB-2
EC 2.7.10.1
Trastuzumab
P188ANX8CK
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
815-828Subventions
Organisme : Associazione Italiana per la Ricerca sul Cancro
ID : 10352
Organisme : Ministero della Salute
ID : RF-2009-1532281
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