Natural compound catechol induces DNA damage, apoptosis, and G1 cell cycle arrest in breast cancer cells

Abstract

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.

Genome-wide identification of resistance genes and response mechanism analysis of key gene knockout strain to catechol in Saccharomyces cerevisiae

“…Catechol has oxidative-reductive activity and can induce further membrane damage. Additionally, after membrane damage, CA can more easily enter cells and cause genetic toxicity such as DNA and protein damage ( Vazhappilly et al, 2021 ). Therefore, these may be the reasons why ERG2 and ERG6 knockout strains are extremely sensitive to CA stress.…”

Lenvatinib resistance mechanism and potential ways to conquer

“…Guo Y et al ( Guo et al, 2021a ) concluded that ATR-CHK1 signaling would be a therapeutic target for liver cancer. As reported, the role of ATR-CHK1 has been considered as a necessary regulator of the DDR, which especially involved in sensing DNA replication stress ( Smith et al, 2020 ; Khazaaleh et al, 2021 ; Vazhappilly et al, 2021 ). Further, this signal could activate oncogene and regulate G1 checkpoint ( Khazaaleh et al, 2021 ).…”

Promoting Apoptosis, a Promising Way to Treat Breast Cancer With Natural Products: A Comprehensive Review

“…In 2021, a study by Vazhappilly et al indicated that catechol could inhibit proliferation and result in apoptosis in MCF-7 cells by activating p53, inhibiting of regulatory proteins such as DNMT1, P-BRCA1, Mcl-1, and PDCD6, and increasing the Bax/Bcl-2 ratio. Ultimately, caspase-mediated cell death is triggered (Vazhappilly et al, 2021). In their study, Sp et al (2021) showed that 6-zingerol might induce apoptosis in MDA-MB-231 and MCF-7 BC cell lines by activating p53, regulating the Bax/ Bcl-2 ratio, and increasing the release of CytoC.…”