All-trans retinoic acid and protein kinase C α/ß1 inhibitor combined treatment targets cancer stem cells and impairs breast tumor progression.
Sci Rep
; 11(1): 6044, 2021 03 15.
Article
in En
| MEDLINE
| ID: mdl-33723318
ABSTRACT
Breast cancer is the leading cause of cancer death among women worldwide. Blocking a single signaling pathway is often an ineffective therapy, especially in the case of aggressive or drug-resistant tumors. Since we have previously described the mechanism involved in the crosstalk between Retinoic Acid system and protein kinase C (PKC) pathway, the rationale of our study was to evaluate the effect of combining all-trans-retinoic acid (ATRA) with a classical PCK inhibitor (Gö6976) in preclinical settings. Employing hormone-independent mammary cancer models, Gö6976 and ATRA combined treatment induced a synergistic reduction in proliferative potential that correlated with an increased apoptosis and RARs modulation towards an anti-oncogenic profile. Combined treatment also impairs growth, self-renewal and clonogenicity potential of cancer stem cells and reduced tumor growth, metastatic spread and cancer stem cells frequency in vivo. An in-silico analysis of "Kaplan-Meier plotter" database indicated that low PKCα together with high RARα mRNA expression is a favorable prognosis factor for hormone-independent breast cancer patients. Here we demonstrate that a classical PKC inhibitor potentiates ATRA antitumor effects also targeting cancer stem cells growth, self-renewal and frequency.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Neoplastic Stem Cells
/
Antineoplastic Combined Chemotherapy Protocols
/
Protein Kinase C-alpha
/
Protein Kinase C beta
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Mammary Neoplasms, Experimental
/
Neoplasm Proteins
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Sci Rep
Year:
2021
Document type:
Article
Affiliation country: