{"title":"富百里醌黑草甲醇提取物促进胰腺癌细胞凋亡：靶向NRF2/HO-1和TNF-α通路","authors":"Sümeyra Çetinkaya, İlknur Çınar Ayan, Hatice Gül Dursun, İpek Süntar, Kevser Taban, Hasya Nazlı Gök, Mithat Atak","doi":"10.2174/0118715206370057250421061226","DOIUrl":null,"url":null,"abstract":"<p><strong>Aims: </strong>This study explores the therapeutic potential of Nigella sativa L. and its key bioactive compound, thymoquinone (TQ).</p><p><strong>Background: </strong>Pancreatic cancer presents a significant health challenge due to its aggressiveness and limited treatment options. N. sativa and its component TQ have demonstrated anticancer properties in other cancers, warranting exploration in pancreatic cancer models.</p><p><strong>Objective: </strong>To assess the antiproliferative, apoptotic, and anti-invasive effects of N. sativa extracts and TQ on pancreatic cancer cells, with a focus on modulating the NRF2/HO-1 and TNF-α signaling pathways.</p><p><strong>Method: </strong>MIA PaCa-2 and PANC-1 pancreatic cancer cell lines were treated with essential and fixed oils, methanol extracts (from Türkiye and Syria), and TQ. Cell viability, apoptosis, and invasiveness were assessed via XTT, Annexin V, and Matrigel assays, respectively. Gene expression and cytokine levels were evaluated using RTqPCR and ELISA. HPLC was conducted to confirm TQ concentrations in extracts.</p><p><strong>Result: </strong>The methanol extract of Türkiye-originated N. sativa seeds (TM) exhibited the highest cytotoxic effect, reducing cell viability in MIA PaCa-2 and PANC-1 at 0.05 mg/mL, while TQ significantly decreased viability at 20 μM. TM reduced MIA PaCa-2 and PANC-1 invasiveness (42±1.23 and 35±0.73, respectively) and contained a higher concentration of TQ (7.9168 ± 0.0561%) compared to the Syria-originated extract (SM).</p><p><strong>Conclusion: </strong>The findings suggest that TM and TQ exhibit strong anticancer potential by modulating key signaling pathways in pancreatic cancer cells, supporting their potential for further development as therapeutic agents in pancreatic cancer treatment.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6000,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Enhanced Apoptosis in Pancreatic Cancer Cells through Thymoquinone-rich Nigella sativa L. Methanol Extract: Targeting NRF2/HO-1 and TNF-α Pathways.\",\"authors\":\"Sümeyra Çetinkaya, İlknur Çınar Ayan, Hatice Gül Dursun, İpek Süntar, Kevser Taban, Hasya Nazlı Gök, Mithat Atak\",\"doi\":\"10.2174/0118715206370057250421061226\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Aims: </strong>This study explores the therapeutic potential of Nigella sativa L. and its key bioactive compound, thymoquinone (TQ).</p><p><strong>Background: </strong>Pancreatic cancer presents a significant health challenge due to its aggressiveness and limited treatment options. N. sativa and its component TQ have demonstrated anticancer properties in other cancers, warranting exploration in pancreatic cancer models.</p><p><strong>Objective: </strong>To assess the antiproliferative, apoptotic, and anti-invasive effects of N. sativa extracts and TQ on pancreatic cancer cells, with a focus on modulating the NRF2/HO-1 and TNF-α signaling pathways.</p><p><strong>Method: </strong>MIA PaCa-2 and PANC-1 pancreatic cancer cell lines were treated with essential and fixed oils, methanol extracts (from Türkiye and Syria), and TQ. Cell viability, apoptosis, and invasiveness were assessed via XTT, Annexin V, and Matrigel assays, respectively. Gene expression and cytokine levels were evaluated using RTqPCR and ELISA. HPLC was conducted to confirm TQ concentrations in extracts.</p><p><strong>Result: </strong>The methanol extract of Türkiye-originated N. sativa seeds (TM) exhibited the highest cytotoxic effect, reducing cell viability in MIA PaCa-2 and PANC-1 at 0.05 mg/mL, while TQ significantly decreased viability at 20 μM. TM reduced MIA PaCa-2 and PANC-1 invasiveness (42±1.23 and 35±0.73, respectively) and contained a higher concentration of TQ (7.9168 ± 0.0561%) compared to the Syria-originated extract (SM).</p><p><strong>Conclusion: </strong>The findings suggest that TM and TQ exhibit strong anticancer potential by modulating key signaling pathways in pancreatic cancer cells, supporting their potential for further development as therapeutic agents in pancreatic cancer treatment.</p>\",\"PeriodicalId\":7934,\"journal\":{\"name\":\"Anti-cancer agents in medicinal chemistry\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":2.6000,\"publicationDate\":\"2025-04-29\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Anti-cancer agents in medicinal chemistry\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.2174/0118715206370057250421061226\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"CHEMISTRY, MEDICINAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Anti-cancer agents in medicinal chemistry","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2174/0118715206370057250421061226","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
Enhanced Apoptosis in Pancreatic Cancer Cells through Thymoquinone-rich Nigella sativa L. Methanol Extract: Targeting NRF2/HO-1 and TNF-α Pathways.
Aims: This study explores the therapeutic potential of Nigella sativa L. and its key bioactive compound, thymoquinone (TQ).
Background: Pancreatic cancer presents a significant health challenge due to its aggressiveness and limited treatment options. N. sativa and its component TQ have demonstrated anticancer properties in other cancers, warranting exploration in pancreatic cancer models.
Objective: To assess the antiproliferative, apoptotic, and anti-invasive effects of N. sativa extracts and TQ on pancreatic cancer cells, with a focus on modulating the NRF2/HO-1 and TNF-α signaling pathways.
Method: MIA PaCa-2 and PANC-1 pancreatic cancer cell lines were treated with essential and fixed oils, methanol extracts (from Türkiye and Syria), and TQ. Cell viability, apoptosis, and invasiveness were assessed via XTT, Annexin V, and Matrigel assays, respectively. Gene expression and cytokine levels were evaluated using RTqPCR and ELISA. HPLC was conducted to confirm TQ concentrations in extracts.
Result: The methanol extract of Türkiye-originated N. sativa seeds (TM) exhibited the highest cytotoxic effect, reducing cell viability in MIA PaCa-2 and PANC-1 at 0.05 mg/mL, while TQ significantly decreased viability at 20 μM. TM reduced MIA PaCa-2 and PANC-1 invasiveness (42±1.23 and 35±0.73, respectively) and contained a higher concentration of TQ (7.9168 ± 0.0561%) compared to the Syria-originated extract (SM).
Conclusion: The findings suggest that TM and TQ exhibit strong anticancer potential by modulating key signaling pathways in pancreatic cancer cells, supporting their potential for further development as therapeutic agents in pancreatic cancer treatment.
期刊介绍：
Formerly: Current Medicinal Chemistry - Anti-Cancer Agents.
Anti-Cancer Agents in Medicinal Chemistry aims to cover all the latest and outstanding developments in medicinal chemistry and rational drug design for the discovery of anti-cancer agents.
Each issue contains a series of timely in-depth reviews and guest edited issues written by leaders in the field covering a range of current topics in cancer medicinal chemistry. The journal only considers high quality research papers for publication.
Anti-Cancer Agents in Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments in cancer drug discovery.
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