Matairesinol Induces Mitochondrial Dysfunction and Exerts Synergistic Anticancer Effects with 5-Fluorouracil in Pancreatic Cancer Cells
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive types of cancer and exhibits a devastating 5-year survival rate. The most recent procedure for the treatment of PDAC is a combination of several conventional chemotherapeutic agents, termed FOLFIRINOX, that includes irinotecan, le...
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MDPI AG
2022-07-01
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| Series: | Marine Drugs |
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| Online Access: | https://www.mdpi.com/1660-3397/20/8/473 |
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| author | Woonghee Lee Gwonhwa Song Hyocheol Bae |
| author_facet | Woonghee Lee Gwonhwa Song Hyocheol Bae |
| author_sort | Woonghee Lee |
| collection | DOAJ |
| description | Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive types of cancer and exhibits a devastating 5-year survival rate. The most recent procedure for the treatment of PDAC is a combination of several conventional chemotherapeutic agents, termed FOLFIRINOX, that includes irinotecan, leucovorin, oxaliplatin, and 5-fluorouracil (5-FU). However, ongoing treatment using these agents is challenging due to their severe side effects and limitations on the range of patients available for PDAC. Therefore, safer and more innovative anticancer agents must be developed. The anticarcinoma activity of matairesinol that can be extracted from seagrass has been reported in various types of cancer, including prostate, breast, cervical, and pancreatic cancer. However, the molecular mechanism of effective anticancer activity of matairesinol against pancreatic cancer remains unclear. In the present study, we confirmed the inhibition of cell proliferation and progression induced by matairesinol in representative human pancreatic cancer cell lines (MIA PaCa-2 and PANC-1). Additionally, matairesinol triggers apoptosis and causes mitochondrial impairment as evidenced by the depolarization of the mitochondrial membrane, disruption of calcium, and suppression of cell migration and related intracellular signaling pathways. Finally, matairesinol exerts a synergistic effect with 5-FU, a standard anticancer agent for PDAC. These results demonstrate the therapeutic potential of matairesinol in the treatment of PDAC. |
| first_indexed | 2024-03-09T04:11:04Z |
| format | Article |
| id | doaj.art-d7170e79043647419bcefad9d919ab31 |
| institution | Directory Open Access Journal |
| issn | 1660-3397 |
| language | English |
| last_indexed | 2024-03-09T04:11:04Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Marine Drugs |
| spelling | doaj.art-d7170e79043647419bcefad9d919ab312023-12-03T14:00:22ZengMDPI AGMarine Drugs1660-33972022-07-0120847310.3390/md20080473Matairesinol Induces Mitochondrial Dysfunction and Exerts Synergistic Anticancer Effects with 5-Fluorouracil in Pancreatic Cancer CellsWoonghee Lee0Gwonhwa Song1Hyocheol Bae2Department of Biotechnology, Institute of Animal Molecular Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02841, KoreaDepartment of Biotechnology, Institute of Animal Molecular Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02841, KoreaDepartment of Oriental Biotechnology, College of Life Sciences, Kyung Hee University, Yongin 17104, KoreaPancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive types of cancer and exhibits a devastating 5-year survival rate. The most recent procedure for the treatment of PDAC is a combination of several conventional chemotherapeutic agents, termed FOLFIRINOX, that includes irinotecan, leucovorin, oxaliplatin, and 5-fluorouracil (5-FU). However, ongoing treatment using these agents is challenging due to their severe side effects and limitations on the range of patients available for PDAC. Therefore, safer and more innovative anticancer agents must be developed. The anticarcinoma activity of matairesinol that can be extracted from seagrass has been reported in various types of cancer, including prostate, breast, cervical, and pancreatic cancer. However, the molecular mechanism of effective anticancer activity of matairesinol against pancreatic cancer remains unclear. In the present study, we confirmed the inhibition of cell proliferation and progression induced by matairesinol in representative human pancreatic cancer cell lines (MIA PaCa-2 and PANC-1). Additionally, matairesinol triggers apoptosis and causes mitochondrial impairment as evidenced by the depolarization of the mitochondrial membrane, disruption of calcium, and suppression of cell migration and related intracellular signaling pathways. Finally, matairesinol exerts a synergistic effect with 5-FU, a standard anticancer agent for PDAC. These results demonstrate the therapeutic potential of matairesinol in the treatment of PDAC.https://www.mdpi.com/1660-3397/20/8/473matairesinolpancreatic cancermitochondria dysfunction5-fluorouracilanticancer drugs |
| spellingShingle | Woonghee Lee Gwonhwa Song Hyocheol Bae Matairesinol Induces Mitochondrial Dysfunction and Exerts Synergistic Anticancer Effects with 5-Fluorouracil in Pancreatic Cancer Cells Marine Drugs matairesinol pancreatic cancer mitochondria dysfunction 5-fluorouracil anticancer drugs |
| title | Matairesinol Induces Mitochondrial Dysfunction and Exerts Synergistic Anticancer Effects with 5-Fluorouracil in Pancreatic Cancer Cells |
| title_full | Matairesinol Induces Mitochondrial Dysfunction and Exerts Synergistic Anticancer Effects with 5-Fluorouracil in Pancreatic Cancer Cells |
| title_fullStr | Matairesinol Induces Mitochondrial Dysfunction and Exerts Synergistic Anticancer Effects with 5-Fluorouracil in Pancreatic Cancer Cells |
| title_full_unstemmed | Matairesinol Induces Mitochondrial Dysfunction and Exerts Synergistic Anticancer Effects with 5-Fluorouracil in Pancreatic Cancer Cells |
| title_short | Matairesinol Induces Mitochondrial Dysfunction and Exerts Synergistic Anticancer Effects with 5-Fluorouracil in Pancreatic Cancer Cells |
| title_sort | matairesinol induces mitochondrial dysfunction and exerts synergistic anticancer effects with 5 fluorouracil in pancreatic cancer cells |
| topic | matairesinol pancreatic cancer mitochondria dysfunction 5-fluorouracil anticancer drugs |
| url | https://www.mdpi.com/1660-3397/20/8/473 |
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