Carnosic acid enhances cisplatin sensitivity and suppresses gastric cancer progression via the TP53/SLC7A11/ALOX12 axis
Abstract Background Gastric cancer (GC) remains a significant global health challenge due to its high mortality and frequent resistance to chemotherapy drugs like cisplatin (DDP). Carnosic acid (CA), a phenolic diterpene, exhibits potential anti-cancer properties. This study aimed to investigate the...
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BMC
2025-07-01
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| Series: | Hereditas |
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| Online Access: | https://doi.org/10.1186/s41065-025-00508-2 |
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| author | Li Zhou Bin Xu Baojian Li |
| author_facet | Li Zhou Bin Xu Baojian Li |
| author_sort | Li Zhou |
| collection | DOAJ |
| description | Abstract Background Gastric cancer (GC) remains a significant global health challenge due to its high mortality and frequent resistance to chemotherapy drugs like cisplatin (DDP). Carnosic acid (CA), a phenolic diterpene, exhibits potential anti-cancer properties. This study aimed to investigate the role of CA in regulating GC development and DDP sensitivity. Methods The half-maximal inhibitory concentration (IC50) of DDP and cell viability were determined using a cell counting kit-8 assay. Cell proliferation was evaluated by a 5-Ethynyl-2’-deoxyuridine assay, while cell migration was assessed by a transwell assay. Cell death was analyzed through flow cytometry, fluorometric assay, and colorimetric assays. The targets of CA were identified using network pharmacology. Western blotting was employed to detect the protein expression of tumor protein p53 (TP53), solute carrier family 7 member 11 (SLC7A11), and arachidonate 12-lipoxygenase, 12 S type (ALOX12). Results CA treatment significantly inhibited GC cell proliferation and migration and enhanced cell death. The treatment also elevated reactive oxygen species (ROS) and Fe2+ levels, while reducing glutathione (GSH) levels and the IC50 value for DDP in GC cells. In addition, TP53 was identified as a target of CA, and its protein expression was upregulated by CA treatment in GC cells. Silencing TP53 attenuated the effects of CA on cell proliferation, migration, death, and the sensitivity of tumor cells to DDP. Further, CA regulated the TP53-mediated SLC7A11/ALOX12 pathway. Conclusion CA improved the sensitivity of GC cells to DDP and inhibited their malignant progression by regulating the TP53-mediated SLC7A11/ALOX12 axis, highlighting its potential clinical significance for GC treatment. |
| format | Article |
| id | doaj-art-6e14fec17cd044378d8d9050d774a4f4 |
| institution | Kabale University |
| issn | 1601-5223 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
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| series | Hereditas |
| spelling | doaj-art-6e14fec17cd044378d8d9050d774a4f42025-08-20T04:02:55ZengBMCHereditas1601-52232025-07-01162111010.1186/s41065-025-00508-2Carnosic acid enhances cisplatin sensitivity and suppresses gastric cancer progression via the TP53/SLC7A11/ALOX12 axisLi Zhou0Bin Xu1Baojian Li2Department of Traditional Chinese Medicine, Changzhou Fourth People’s HospitalDepartment of Traditional Chinese Medicine, Changzhou Fourth People’s HospitalDepartment of Pharmacy, The Fourth People’s Hospital of ChangzhouAbstract Background Gastric cancer (GC) remains a significant global health challenge due to its high mortality and frequent resistance to chemotherapy drugs like cisplatin (DDP). Carnosic acid (CA), a phenolic diterpene, exhibits potential anti-cancer properties. This study aimed to investigate the role of CA in regulating GC development and DDP sensitivity. Methods The half-maximal inhibitory concentration (IC50) of DDP and cell viability were determined using a cell counting kit-8 assay. Cell proliferation was evaluated by a 5-Ethynyl-2’-deoxyuridine assay, while cell migration was assessed by a transwell assay. Cell death was analyzed through flow cytometry, fluorometric assay, and colorimetric assays. The targets of CA were identified using network pharmacology. Western blotting was employed to detect the protein expression of tumor protein p53 (TP53), solute carrier family 7 member 11 (SLC7A11), and arachidonate 12-lipoxygenase, 12 S type (ALOX12). Results CA treatment significantly inhibited GC cell proliferation and migration and enhanced cell death. The treatment also elevated reactive oxygen species (ROS) and Fe2+ levels, while reducing glutathione (GSH) levels and the IC50 value for DDP in GC cells. In addition, TP53 was identified as a target of CA, and its protein expression was upregulated by CA treatment in GC cells. Silencing TP53 attenuated the effects of CA on cell proliferation, migration, death, and the sensitivity of tumor cells to DDP. Further, CA regulated the TP53-mediated SLC7A11/ALOX12 pathway. Conclusion CA improved the sensitivity of GC cells to DDP and inhibited their malignant progression by regulating the TP53-mediated SLC7A11/ALOX12 axis, highlighting its potential clinical significance for GC treatment.https://doi.org/10.1186/s41065-025-00508-2Carnosic acidGastric cancerCisplatinTP53 |
| spellingShingle | Li Zhou Bin Xu Baojian Li Carnosic acid enhances cisplatin sensitivity and suppresses gastric cancer progression via the TP53/SLC7A11/ALOX12 axis Hereditas Carnosic acid Gastric cancer Cisplatin TP53 |
| title | Carnosic acid enhances cisplatin sensitivity and suppresses gastric cancer progression via the TP53/SLC7A11/ALOX12 axis |
| title_full | Carnosic acid enhances cisplatin sensitivity and suppresses gastric cancer progression via the TP53/SLC7A11/ALOX12 axis |
| title_fullStr | Carnosic acid enhances cisplatin sensitivity and suppresses gastric cancer progression via the TP53/SLC7A11/ALOX12 axis |
| title_full_unstemmed | Carnosic acid enhances cisplatin sensitivity and suppresses gastric cancer progression via the TP53/SLC7A11/ALOX12 axis |
| title_short | Carnosic acid enhances cisplatin sensitivity and suppresses gastric cancer progression via the TP53/SLC7A11/ALOX12 axis |
| title_sort | carnosic acid enhances cisplatin sensitivity and suppresses gastric cancer progression via the tp53 slc7a11 alox12 axis |
| topic | Carnosic acid Gastric cancer Cisplatin TP53 |
| url | https://doi.org/10.1186/s41065-025-00508-2 |
| work_keys_str_mv | AT lizhou carnosicacidenhancescisplatinsensitivityandsuppressesgastriccancerprogressionviathetp53slc7a11alox12axis AT binxu carnosicacidenhancescisplatinsensitivityandsuppressesgastriccancerprogressionviathetp53slc7a11alox12axis AT baojianli carnosicacidenhancescisplatinsensitivityandsuppressesgastriccancerprogressionviathetp53slc7a11alox12axis |