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Natural compound catechol induces DNA damage, apoptosis, and G1 cell cycle arrest in breast cancer cells
Author(s) -
Vazhappilly Cijo George,
Hodeify Rawad,
Siddiqui Shoib Sarwar,
Laham Amina Jamal,
Me Varsha,
ElAwady Raafat,
Matar Rachel,
Merheb Maxime,
Marton John,
Al Zouabi Hussain Abdel Karim,
Radhakrishnan Rajan
Publication year - 2021
Publication title -
phytotherapy research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.019
H-Index - 129
eISSN - 1099-1573
pISSN - 0951-418X
DOI - 10.1002/ptr.6970
Subject(s) - cell cycle checkpoint , cell cycle , apoptosis , dna damage , cancer cell , programmed cell death , cell growth , cancer research , cyclin d1 , cancer , biology , chemistry , microbiology and biotechnology , biochemistry , dna , genetics
Targeting cell cycle and inducing DNA damage by activating cell death pathways are considered as effective therapeutic strategy for combating breast cancer progression. Many of the naturally known small molecules target these signaling pathways and are effective against resistant and/or aggressive types of breast cancers. Here, we investigated the effect of catechol, a naturally occurring plant compound, for its specificity and chemotherapeutic efficacies in breast cancer (MCF‐7 and MDA‐MB‐231) cells. Catechol treatment showed concentration‐dependent cytotoxicity and antiproliferative growth in both MCF‐7 and MDA‐MB‐231 cells while sparing minimal effects on noncancerous (F‐180 and HK2) cells. Catechol modulated differential DNA damage effects by activating ATM/ATR pathways and showed enhanced γ–H2AX expression, as an indicator for DNA double‐stranded breaks. MCF‐7 cells showed G1 cell cycle arrest by regulating p21‐mediated cyclin E/Cdk2 inhibition. Furthermore, activation of p53 triggered a caspase‐mediated cell death mechanism by inhibiting regulatory proteins such as DNMT1, p‐BRCA1, MCL‐1, and PDCD6 with an increased Bax/Bcl‐2 ratio. Overall, our results showed that catechol possesses favorable safety profile for noncancerous cells while specifically targeting multiple signaling cascades to inhibit proliferation in breast cancer cells.