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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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.958443/full |
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| author | Umar Mehraj Nissar Ahmad Wani Abid Hamid Mustfa Alkhanani Abdullah Almilaibary Manzoor Ahmad Mir |
| author_facet | Umar Mehraj Nissar Ahmad Wani Abid Hamid Mustfa Alkhanani Abdullah Almilaibary Manzoor Ahmad Mir |
| author_sort | Umar Mehraj |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-10T17:12:47Z |
| format | Article |
| id | doaj.art-e25dcab2afa949f89ef3b4c3de36057d |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-10T17:12:47Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-e25dcab2afa949f89ef3b4c3de36057d2022-12-22T01:40:16ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-08-011310.3389/fphar.2022.958443958443Adapalene inhibits the growth of triple-negative breast cancer cells by S-phase arrest and potentiates the antitumor efficacy of GDC-0941Umar Mehraj0Nissar Ahmad Wani1Abid Hamid2Mustfa Alkhanani3Abdullah Almilaibary4Manzoor Ahmad Mir5Department of Bioresources, School of Biological Sciences, University of Kashmir, Srinagar, J&K, IndiaDepartment of Biotechnology, School of Life Sciences, Central University of Kashmir, Ganderbal, J&K, IndiaDepartment of Biotechnology, School of Life Sciences, Central University of Kashmir, Ganderbal, J&K, IndiaBiology Department, College of Science, University of Hafr Al Batin, Hafr Al Batin, Saudi ArabiaDepartment of Family and Community Medicine, Albaha University, Albaha, Saudi ArabiaDepartment of Bioresources, School of Biological Sciences, University of Kashmir, Srinagar, J&K, IndiaAlthough 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.https://www.frontiersin.org/articles/10.3389/fphar.2022.958443/fullBreast cancertriple-negative breast canceradapalenecombination therapyChou–TalalayGDC-0941 |
| spellingShingle | Umar Mehraj Nissar Ahmad Wani Abid Hamid Mustfa Alkhanani Abdullah Almilaibary Manzoor Ahmad Mir Adapalene inhibits the growth of triple-negative breast cancer cells by S-phase arrest and potentiates the antitumor efficacy of GDC-0941 Frontiers in Pharmacology Breast cancer triple-negative breast cancer adapalene combination therapy Chou–Talalay GDC-0941 |
| title | Adapalene inhibits the growth of triple-negative breast cancer cells by S-phase arrest and potentiates the antitumor efficacy of GDC-0941 |
| title_full | Adapalene inhibits the growth of triple-negative breast cancer cells by S-phase arrest and potentiates the antitumor efficacy of GDC-0941 |
| title_fullStr | Adapalene inhibits the growth of triple-negative breast cancer cells by S-phase arrest and potentiates the antitumor efficacy of GDC-0941 |
| title_full_unstemmed | Adapalene inhibits the growth of triple-negative breast cancer cells by S-phase arrest and potentiates the antitumor efficacy of GDC-0941 |
| title_short | Adapalene inhibits the growth of triple-negative breast cancer cells by S-phase arrest and potentiates the antitumor efficacy of GDC-0941 |
| title_sort | adapalene inhibits the growth of triple negative breast cancer cells by s phase arrest and potentiates the antitumor efficacy of gdc 0941 |
| topic | Breast cancer triple-negative breast cancer adapalene combination therapy Chou–Talalay GDC-0941 |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.958443/full |
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