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Published on: May 12, 2020
Differential Cytotoxicity of Hydroxycinnamic Acids in Cancer Cells: Structure-Activity Insights From a Broad Panel of
Kadriye Aslıhan Onat Taşdelen1, Merve Sezer Kürkçü2,3, Hatice Öztürkel Kabakaş1
1Graduate School of Natural and Applied Science, Biology, Muğla Sıtkı Koçman University, Muğla, Türkiye.
Abstract:
Phenolic acids, abundant in plant-based foods, are increasingly investigated for their anticancer potential. This study systematically evaluated the cytotoxic effects of three hydroxycinnamic acids-trans-cinnamic acid (tCA), p-coumaric acid (pCA), and ferulic acid (FA)-across 10 cancer cell lines (A-673, HeLa, PC-3, SW48, HT-29, Caco-2, HUH-7, MG-63, 2A3, CARM-L12-TG3) and one non-cancerous cell line (Phoenix) after 48 and 72 h of treatment. IC50 values were determined via MTT assay. At 48 h, tCA showed the most significant reduction in metabolic activity in Caco-2 and HUH-7 cells, while HT-29 was the most resistant. pCA showed selective potency in A-673 and PC-3 cells, whereas FA demonstrated broad cytotoxic activity, with pronounced effects in SW48 and HeLa cells. Cytotoxicity increased in a time-dependent manner at 72 h. The non-cancerous Phoenix cells were generally less sensitive, supporting the selective inhibitory effect of these compounds toward malignant cells. Statistical analyses revealed highly significant effects of treatment and time factors, with significant treatment and time interactions in A-673, HeLa, and PC-3 cells. These findings indicate that pCA is the most selective compound, FA exerts the broadest cytotoxicity, and tCA shows a balanced but time-dependent effect. Collectively, this study highlights hydroxycinnamic acids as promising scaffolds for developing selective anticancer agents.
Insights
This study reveals that hydroxycinnamic acids, like p-coumaric acid and ferulic acid, show promising selective anticancer effects against various cancer cell lines. These plant-derived compounds demonstrate varying potencies and broad cytotoxicity, highlighting their potential in cancer treatment.
Area of Science:
- Biochemistry and Molecular Biology
- Pharmacology and Toxicology
- Plant-based Medicine
Background:
- Phenolic acids from plant sources are recognized for their potential anticancer properties.
- Hydroxycinnamic acids, including trans-cinnamic acid (tCA), p-coumaric acid (pCA), and ferulic acid (FA), are key compounds under investigation.
- Understanding their selective cytotoxicity against cancer cells is crucial for therapeutic development.
Purpose of the Study:
- To systematically evaluate the cytotoxic effects of tCA, pCA, and FA on 10 distinct cancer cell lines and one non-cancerous cell line.
- To determine the dose-dependent and time-dependent cytotoxicity of these phenolic acids.
- To assess the selectivity of these compounds towards malignant cells.
Main Methods:
- Utilized MTT assay to determine IC50 values for tCA, pCA, and FA.
- Treated A-673, HeLa, PC-3, SW48, HT-29, Caco-2, HUH-7, MG-63, 2A3, CARM-L12-TG3, and Phoenix cell lines.
- Assessed cytotoxicity at 48 and 72 hours post-treatment.
Main Results:
- pCA exhibited selective potency against A-673 and PC-3 cells.
- FA demonstrated broad cytotoxicity, particularly effective against SW48 and HeLa cells.
- tCA showed significant effects on Caco-2 and HUH-7 cells, with increased cytotoxicity over time.
- Non-cancerous Phoenix cells displayed lower sensitivity, indicating selective action.
Conclusions:
- pCA is identified as the most selective hydroxycinnamic acid.
- FA exhibits the broadest cytotoxic activity among the tested compounds.
- Hydroxycinnamic acids represent promising scaffolds for developing targeted anticancer therapies.
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