Natural compound catechol induces DNA damage, apoptosis, and G1 cell cycle arrest in breast cancer cells
Cijo George Vazhappilly1, Rawad Hodeify1, Shoib Sarwar Siddiqui1
1Department of Biotechnology, American University of Ras Al Khaimah, Ras Al Khaimah, United Arab Emirates.
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.
Insights
Catechol, a plant compound, effectively inhibits breast cancer cell growth and proliferation by inducing DNA damage and activating cell death pathways. It shows a favorable safety profile, sparing noncancerous cells while targeting cancer cells specifically.
Area of Science:
- Biochemistry
- Molecular Biology
- Pharmacology
Background:
- Targeting cell cycle and DNA damage pathways are key strategies for breast cancer therapy.
- Natural small molecules show promise against resistant and aggressive breast cancers.
Purpose of the Study:
- To investigate the chemotherapeutic efficacy and specificity of catechol in breast cancer cells.
- To elucidate the mechanisms underlying catechol's anti-cancer effects.
Main Methods:
- Assessing catechol's cytotoxicity and antiproliferative effects on MCF-7 and MDA-MB-231 breast cancer cells and noncancerous cells.
- Analyzing DNA damage response via ATM/ATR pathways and γ-H2AX expression.
- Investigating cell cycle arrest (G1 phase) and apoptosis induction through p53, caspase activation, and key protein regulation (p21, DNMT1, p-BRCA1, MCL-1, PDCD6, Bax/Bcl-2).
Main Results:
- Catechol demonstrated concentration-dependent cytotoxicity and antiproliferative effects on breast cancer cells, with minimal impact on noncancerous cells.
- Catechol induced DNA double-strand breaks via ATM/ATR activation and enhanced γ-H2AX expression.
- Catechol caused G1 cell cycle arrest in MCF-7 cells and triggered apoptosis by modulating p53, caspase pathways, and key regulatory proteins, leading to an increased Bax/Bcl-2 ratio.
Conclusions:
- Catechol exhibits a favorable safety profile against noncancerous cells.
- Catechol effectively targets multiple signaling cascades to inhibit breast cancer cell proliferation and induce cell death.
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