TY - JOUR
T1 - Natural compound catechol induces DNA damage, apoptosis, and G1 cell cycle arrest in breast cancer cells
AU - Vazhappilly, Cijo George
AU - Hodeify, Rawad
AU - Siddiqui, Shoib Sarwar
AU - Laham, Amina Jamal
AU - Menon, Varsha
AU - El-Awady, Raafat
AU - Matar, Rachel
AU - Merheb, Maxime
AU - Marton, John
AU - Al Zouabi, Hussain Abdel Karim
AU - Radhakrishnan, Rajan
N1 - © 2020 John Wiley & Sons, Ltd.
PY - 2020/12/7
Y1 - 2020/12/7
N2 - 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.
AB - 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.
U2 - 10.1002/ptr.6970
DO - 10.1002/ptr.6970
M3 - Article
C2 - 33289235
SN - 0951-418X
JO - Phytotherapy Research
JF - Phytotherapy Research
ER -