University of Hertfordshire

  • Cijo George Vazhappilly
  • Rawad Hodeify
  • Shoib Sarwar Siddiqui
  • Amina Jamal Laham
  • Varsha Menon
  • Raafat El-Awady
  • Rachel Matar
  • Maxime Merheb
  • John Marton
  • Hussain Abdel Karim Al Zouabi
  • Rajan Radhakrishnan
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Original languageEnglish
Number of pages15
JournalPhytotherapy Research
Early online date7 Dec 2020
DOIs
Publication statusE-pub ahead of print - 7 Dec 2020

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.

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