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

• Published in: Phytotherapy research Vol. 35; no. 4; pp. 2185 - 2199
• Main Authors: Vazhappilly, Cijo George, Hodeify, Rawad, Siddiqui, Shoib Sarwar, Laham, Amina Jamal, Menon, Varsha, El‐Awady, Raafat, Matar, Rachel, Merheb, Maxime, Marton, John, Al Zouabi, Hussain Abdel Karim, Radhakrishnan, Rajan
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01-04-2021; Wiley Subscription Services, Inc
• Subjects: Apoptosis; Apoptosis - drug effects; BAX protein; BRCA1 protein; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - genetics; Caspase; caspases; Catechol; Catechols - pharmacology; Catechols - therapeutic use; Cell cycle; Cell death; Cell Line, Tumor; Cell proliferation; Cyclin E; Cyclin-dependent kinase 2; Cytotoxicity; Damage; Deoxyribonucleic acid; DNA; DNA damage; DNA Damage - genetics; DNMT1 protein; Female; G1 Phase Cell Cycle Checkpoints - drug effects; Gene expression; Humans; p53 Protein; Regulatory proteins; Signal transduction; Signal Transduction - drug effects; Signaling; Toxicity; catechol; apoptosis; breast cancer; cell cycle; caspases; DNA damage
• ISSN: 0951-418X; 1099-1573
• DOI: 10.1002/ptr.6970

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.