2′-Hydroxycinnamaldehyde induces ROS-mediated apoptosis in cancer cells by targeting PRX1 and PRX2
2′-Hydroxycinnamaldehyde (HCA) is a component of the commonly used spice cinnamon, which has beneficial effects on cancer, allergies, bacterial/viral infections, and Alzheimer’s disease. Our previous study showed that HCA induced reactive oxygen species (ROS) and apoptosis in cancer cells, and pretr...
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Elsevier
2025-01-01
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| Series: | Results in Chemistry |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211715624006271 |
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| author | Yae Jin Yoon Yu-Jin Lee Jiyeon Choi Seung-Wook Chi Sangku Lee Kyung Chan Park Byoung-Mog Kwon Dong Cho Han |
| author_facet | Yae Jin Yoon Yu-Jin Lee Jiyeon Choi Seung-Wook Chi Sangku Lee Kyung Chan Park Byoung-Mog Kwon Dong Cho Han |
| author_sort | Yae Jin Yoon |
| collection | DOAJ |
| description | 2′-Hydroxycinnamaldehyde (HCA) is a component of the commonly used spice cinnamon, which has beneficial effects on cancer, allergies, bacterial/viral infections, and Alzheimer’s disease. Our previous study showed that HCA induced reactive oxygen species (ROS) and apoptosis in cancer cells, and pretreatment of cancer cells with antioxidants abolished HCA-mediated ROS production and apoptosis. This indicates that ROS are critical effector for HCA activity. However, the molecular target of HCA for ROS induction has not been identified. In the present study, we identified peroxiredoxin 1 (PRX1) and peroxiredoxin 2 (PRX2) as target proteins of HCA using affinity chromatography, and further confirmed these association using a cellular thermal shift assay (CETSA). In addition, we used mutagenesis to identify important cysteine residues in PRX1 for HCA binding. PRX1 has four cysteines (Cys52, Cys71, Cys83, and Cys173), and when Cys173 (but not the other cysteine sites) was mutated to serine, it was unable to bind biotin-conjugated HCA, suggesting that Cys173 is important for HCA binding. Treatment of SW620 cancer cells transfected by control vector with 20 μM HCA increased ROS levels by 5.2-fold compared to DMSO-treated cells. However, downregulation of target proteins PRX1 and PRX2 using shRNAs (short hairpin RNA) significantly reduced HCA-mediated ROS induction (1.6-fold), supporting that PRX1 and PRX2 are targets of HCA for ROS elevation. Additionally, intraperitoneal injection of 50 mg/kg HCA inhibited SW620 tumor growth, resulting in a 59.9 % reduction in tumor volume. CETSA analysis of tumor tissues showed that PRX1 and PRX2 were bound and thus inactivated by HCA in a mouse xenograft model. These findings demonstrate that PRX1 and PRX2 are molecular target proteins responsible for HCA-induced ROS elevation and cancer cell death. |
| format | Article |
| id | doaj-art-2a40fc64cf2b44f78547b6a1f7d16573 |
| institution | Kabale University |
| issn | 2211-7156 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Results in Chemistry |
| spelling | doaj-art-2a40fc64cf2b44f78547b6a1f7d165732025-01-29T05:00:36ZengElsevierResults in Chemistry2211-71562025-01-01131019312′-Hydroxycinnamaldehyde induces ROS-mediated apoptosis in cancer cells by targeting PRX1 and PRX2Yae Jin Yoon0Yu-Jin Lee1Jiyeon Choi2Seung-Wook Chi3Sangku Lee4Kyung Chan Park5Byoung-Mog Kwon6Dong Cho Han7Laboratory of Chemical Biology and Genomics, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahakro Daejeon 34141, Republic of KoreaPersonalized Genomic Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahakro Daejeon 34141, Republic of KoreaLaboratory of Chemical Biology and Genomics, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahakro Daejeon 34141, Republic of KoreaMedical Proteomics Research Center, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahakro Daejeon 34141, Republic of Korea; University of Science and Technology in Korea, Daejeon 34113, Republic of KoreaChemical Biology Research Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju 28116, Republic of KoreaPersonalized Genomic Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahakro Daejeon 34141, Republic of Korea; University of Science and Technology in Korea, Daejeon 34113, Republic of KoreaLaboratory of Chemical Biology and Genomics, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahakro Daejeon 34141, Republic of Korea; University of Science and Technology in Korea, Daejeon 34113, Republic of Korea; Corresponding author at: Central Research Institute, VS PharmTech Co. Ltd., Daejeon 35209, Republic of Korea.Personalized Genomic Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahakro Daejeon 34141, Republic of Korea; University of Science and Technology in Korea, Daejeon 34113, Republic of Korea; Corresponding author at: Personalized Genomic Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahakro Daejeon 34141, Republic of Korea.2′-Hydroxycinnamaldehyde (HCA) is a component of the commonly used spice cinnamon, which has beneficial effects on cancer, allergies, bacterial/viral infections, and Alzheimer’s disease. Our previous study showed that HCA induced reactive oxygen species (ROS) and apoptosis in cancer cells, and pretreatment of cancer cells with antioxidants abolished HCA-mediated ROS production and apoptosis. This indicates that ROS are critical effector for HCA activity. However, the molecular target of HCA for ROS induction has not been identified. In the present study, we identified peroxiredoxin 1 (PRX1) and peroxiredoxin 2 (PRX2) as target proteins of HCA using affinity chromatography, and further confirmed these association using a cellular thermal shift assay (CETSA). In addition, we used mutagenesis to identify important cysteine residues in PRX1 for HCA binding. PRX1 has four cysteines (Cys52, Cys71, Cys83, and Cys173), and when Cys173 (but not the other cysteine sites) was mutated to serine, it was unable to bind biotin-conjugated HCA, suggesting that Cys173 is important for HCA binding. Treatment of SW620 cancer cells transfected by control vector with 20 μM HCA increased ROS levels by 5.2-fold compared to DMSO-treated cells. However, downregulation of target proteins PRX1 and PRX2 using shRNAs (short hairpin RNA) significantly reduced HCA-mediated ROS induction (1.6-fold), supporting that PRX1 and PRX2 are targets of HCA for ROS elevation. Additionally, intraperitoneal injection of 50 mg/kg HCA inhibited SW620 tumor growth, resulting in a 59.9 % reduction in tumor volume. CETSA analysis of tumor tissues showed that PRX1 and PRX2 were bound and thus inactivated by HCA in a mouse xenograft model. These findings demonstrate that PRX1 and PRX2 are molecular target proteins responsible for HCA-induced ROS elevation and cancer cell death.http://www.sciencedirect.com/science/article/pii/S2211715624006271Natural productColon cancerReactive oxygen speciesAntioxidantPeroxiredoxin |
| spellingShingle | Yae Jin Yoon Yu-Jin Lee Jiyeon Choi Seung-Wook Chi Sangku Lee Kyung Chan Park Byoung-Mog Kwon Dong Cho Han 2′-Hydroxycinnamaldehyde induces ROS-mediated apoptosis in cancer cells by targeting PRX1 and PRX2 Results in Chemistry Natural product Colon cancer Reactive oxygen species Antioxidant Peroxiredoxin |
| title | 2′-Hydroxycinnamaldehyde induces ROS-mediated apoptosis in cancer cells by targeting PRX1 and PRX2 |
| title_full | 2′-Hydroxycinnamaldehyde induces ROS-mediated apoptosis in cancer cells by targeting PRX1 and PRX2 |
| title_fullStr | 2′-Hydroxycinnamaldehyde induces ROS-mediated apoptosis in cancer cells by targeting PRX1 and PRX2 |
| title_full_unstemmed | 2′-Hydroxycinnamaldehyde induces ROS-mediated apoptosis in cancer cells by targeting PRX1 and PRX2 |
| title_short | 2′-Hydroxycinnamaldehyde induces ROS-mediated apoptosis in cancer cells by targeting PRX1 and PRX2 |
| title_sort | 2 hydroxycinnamaldehyde induces ros mediated apoptosis in cancer cells by targeting prx1 and prx2 |
| topic | Natural product Colon cancer Reactive oxygen species Antioxidant Peroxiredoxin |
| url | http://www.sciencedirect.com/science/article/pii/S2211715624006271 |
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