Adapalene inhibits the growth of triple-negative breast cancer cells by S-phase arrest and potentiates the antitumor efficacy of GDC-0941

Although advances in diagnostics and therapeutics have prolonged the survival of triple-negative breast cancer (TNBC) patients, metastasis, therapeutic resistance, and lack of targeted therapies remain the foremost hurdle in the effective management of TNBC. Thus, evaluation of new therapeutic agent...

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Published in:Frontiers in pharmacology Vol. 13; p. 958443
Main Authors: Mehraj, Umar, Wani, Nissar Ahmad, Hamid, Abid, Alkhanani, Mustfa, Almilaibary, Abdullah, Mir, Manzoor Ahmad
Format: Journal Article
Language:English
Published: Frontiers Media S.A 08.08.2022
Subjects:
adapalene
Breast cancer
Chou–Talalay
combination therapy
GDC-0941
Pharmacology
triple-negative breast cancer
ISSN:1663-9812, 1663-9812
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Summary:Although advances in diagnostics and therapeutics have prolonged the survival of triple-negative breast cancer (TNBC) patients, metastasis, therapeutic resistance, and lack of targeted therapies remain the foremost hurdle in the effective management of TNBC. Thus, evaluation of new therapeutic agents and their efficacy in combination therapy is urgently needed. The third-generation retinoid adapalene (ADA) has potent antitumor activity, and using ADA in combination with existing therapeutic regimens may improve the effectiveness and minimize the toxicities and drug resistance. The current study aimed to assess the anticancer efficacy of adapalene as a combination regimen with the PI3K inhibitor (GDC-0941) in TNBC in vitro models. The Chou–Talalay’s method evaluated the pharmacodynamic interactions (synergism, antagonism, or additivity) of binary drug combinations. Flow cytometry, Western blotting, and in silico studies were used to analyze the mechanism of GDC–ADA synergistic interactions in TNBC cells. The combination of GDC and ADA demonstrated a synergistic effect in inhibiting proliferation, migration, and colony formation of tumor cells. Accumulation of reactive oxygen species upon co-treatment with GDC and ADA promoted apoptosis and enhanced sensitivity to GDC in TNBC cells. The findings indicate that ADA is a promising therapeutic agent in treating advanced BC tumors and enhance sensitivity to GDC in inhibiting tumor growth in TNBC models while reducing therapeutic resistance.
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Martin Perez-Santos, Benemérita Universidad Autónoma de Puebla, Mexico
Edited by: Andrea Cavazzoni, University of Parma, Italy
This article was submitted to Pharmacology of Anti-Cancer Drugs, a section of the journal Frontiers in Pharmacology
Reviewed by: Kamal Eltayeb, University of Parma, Italy
ISSN:1663-9812
1663-9812
DOI:10.3389/fphar.2022.958443