All-trans retinoic acid and protein kinase C α/β1 inhibitor combined treatment targets cancer stem cells and impairs breast tumor progression. Academic Article uri icon

Overview

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.

publication date

  • March 15, 2021

Research

keywords

  • Antineoplastic Combined Chemotherapy Protocols
  • Mammary Neoplasms, Experimental
  • Neoplasm Proteins
  • Neoplastic Stem Cells
  • Protein Kinase C beta
  • Protein Kinase C-alpha

Identity

PubMed Central ID

  • PMC7961031

Scopus Document Identifier

  • 85102520120

Digital Object Identifier (DOI)

  • 10.1158/0008-5472.CAN-09-2968

PubMed ID

  • 33723318

Additional Document Info

volume

  • 11

issue

  • 1