The Natural Product Parthenolide Inhibits Both Angiogenesis and Invasiveness and Improves Gemcitabine Resistance by Suppressing Nuclear Factor κB Activation in Pancreatic Cancer Cell Lines
We previously established pancreatic cancer (PaCa) cell lines resistant to gemcitabine and found that the activity of nuclear factor κB (NF-κB) was enhanced upon the acquisition of gemcitabine resistance. Parthenolide, the main active ingredient in feverfew, has been reported to exhibit antitumor ac...
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MDPI AG
2024-02-01
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| Series: | Nutrients |
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| Online Access: | https://www.mdpi.com/2072-6643/16/5/705 |
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| author | Yuki Denda Yoichi Matsuo Saburo Sugita Yuki Eguchi Keisuke Nonoyama Hiromichi Murase Tomokatsu Kato Hiroyuki Imafuji Kenta Saito Mamoru Morimoto Ryo Ogawa Hiroki Takahashi Akira Mitsui Masahiro Kimura Shuji Takiguchi |
| author_facet | Yuki Denda Yoichi Matsuo Saburo Sugita Yuki Eguchi Keisuke Nonoyama Hiromichi Murase Tomokatsu Kato Hiroyuki Imafuji Kenta Saito Mamoru Morimoto Ryo Ogawa Hiroki Takahashi Akira Mitsui Masahiro Kimura Shuji Takiguchi |
| author_sort | Yuki Denda |
| collection | DOAJ |
| description | We previously established pancreatic cancer (PaCa) cell lines resistant to gemcitabine and found that the activity of nuclear factor κB (NF-κB) was enhanced upon the acquisition of gemcitabine resistance. Parthenolide, the main active ingredient in feverfew, has been reported to exhibit antitumor activity by suppressing the NF-κB signaling pathway in several types of cancers. However, the antitumor effect of parthenolide on gemcitabine-resistant PaCa has not been elucidated. Here, we confirmed that parthenolide significantly inhibits the proliferation of both gemcitabine-resistant and normal PaCa cells at concentrations of 10 µM and higher, and that the NF-κB activity is significantly inhibited, even by 1 µM parthenolide. In Matrigel invasion assays and angiogenesis assays, the invasive and angiogenic potentials were higher in gemcitabine-resistant than normal PaCa cells and were inhibited by a low concentration of parthenolide. Furthermore, Western blotting showed suppressed MRP1 expression in gemcitabine-resistant PaCa treated with a low parthenolide concentration. In a colony formation assay, the addition of 1 µM parthenolide improved the sensitivity of gemcitabine-resistant PaCa cell lines to gemcitabine. These results suggest that parthenolide may be used as a novel therapeutic agent for the treatment of gemcitabine-resistant PaCa. |
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| issn | 2072-6643 |
| language | English |
| last_indexed | 2024-04-25T00:22:29Z |
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| series | Nutrients |
| spelling | doaj.art-b969aef5a19c453293d7e293f4a007842024-03-12T16:52:17ZengMDPI AGNutrients2072-66432024-02-0116570510.3390/nu16050705The Natural Product Parthenolide Inhibits Both Angiogenesis and Invasiveness and Improves Gemcitabine Resistance by Suppressing Nuclear Factor κB Activation in Pancreatic Cancer Cell LinesYuki Denda0Yoichi Matsuo1Saburo Sugita2Yuki Eguchi3Keisuke Nonoyama4Hiromichi Murase5Tomokatsu Kato6Hiroyuki Imafuji7Kenta Saito8Mamoru Morimoto9Ryo Ogawa10Hiroki Takahashi11Akira Mitsui12Masahiro Kimura13Shuji Takiguchi14Department of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Sciences, 1-Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, JapanDepartment of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Sciences, 1-Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, JapanDepartment of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Sciences, 1-Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, JapanDepartment of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Sciences, 1-Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, JapanDepartment of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Sciences, 1-Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, JapanDepartment of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Sciences, 1-Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, JapanDepartment of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Sciences, 1-Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, JapanDepartment of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Sciences, 1-Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, JapanDepartment of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Sciences, 1-Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, JapanDepartment of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Sciences, 1-Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, JapanDepartment of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Sciences, 1-Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, JapanDepartment of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Sciences, 1-Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, JapanDepartment of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Sciences, 1-Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, JapanDepartment of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Sciences, 1-Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, JapanDepartment of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Sciences, 1-Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, JapanWe previously established pancreatic cancer (PaCa) cell lines resistant to gemcitabine and found that the activity of nuclear factor κB (NF-κB) was enhanced upon the acquisition of gemcitabine resistance. Parthenolide, the main active ingredient in feverfew, has been reported to exhibit antitumor activity by suppressing the NF-κB signaling pathway in several types of cancers. However, the antitumor effect of parthenolide on gemcitabine-resistant PaCa has not been elucidated. Here, we confirmed that parthenolide significantly inhibits the proliferation of both gemcitabine-resistant and normal PaCa cells at concentrations of 10 µM and higher, and that the NF-κB activity is significantly inhibited, even by 1 µM parthenolide. In Matrigel invasion assays and angiogenesis assays, the invasive and angiogenic potentials were higher in gemcitabine-resistant than normal PaCa cells and were inhibited by a low concentration of parthenolide. Furthermore, Western blotting showed suppressed MRP1 expression in gemcitabine-resistant PaCa treated with a low parthenolide concentration. In a colony formation assay, the addition of 1 µM parthenolide improved the sensitivity of gemcitabine-resistant PaCa cell lines to gemcitabine. These results suggest that parthenolide may be used as a novel therapeutic agent for the treatment of gemcitabine-resistant PaCa.https://www.mdpi.com/2072-6643/16/5/705parthenolidepancreatic cancergemcitabine resistanceNF-κBinvasionangiogenesis |
| spellingShingle | Yuki Denda Yoichi Matsuo Saburo Sugita Yuki Eguchi Keisuke Nonoyama Hiromichi Murase Tomokatsu Kato Hiroyuki Imafuji Kenta Saito Mamoru Morimoto Ryo Ogawa Hiroki Takahashi Akira Mitsui Masahiro Kimura Shuji Takiguchi The Natural Product Parthenolide Inhibits Both Angiogenesis and Invasiveness and Improves Gemcitabine Resistance by Suppressing Nuclear Factor κB Activation in Pancreatic Cancer Cell Lines Nutrients parthenolide pancreatic cancer gemcitabine resistance NF-κB invasion angiogenesis |
| title | The Natural Product Parthenolide Inhibits Both Angiogenesis and Invasiveness and Improves Gemcitabine Resistance by Suppressing Nuclear Factor κB Activation in Pancreatic Cancer Cell Lines |
| title_full | The Natural Product Parthenolide Inhibits Both Angiogenesis and Invasiveness and Improves Gemcitabine Resistance by Suppressing Nuclear Factor κB Activation in Pancreatic Cancer Cell Lines |
| title_fullStr | The Natural Product Parthenolide Inhibits Both Angiogenesis and Invasiveness and Improves Gemcitabine Resistance by Suppressing Nuclear Factor κB Activation in Pancreatic Cancer Cell Lines |
| title_full_unstemmed | The Natural Product Parthenolide Inhibits Both Angiogenesis and Invasiveness and Improves Gemcitabine Resistance by Suppressing Nuclear Factor κB Activation in Pancreatic Cancer Cell Lines |
| title_short | The Natural Product Parthenolide Inhibits Both Angiogenesis and Invasiveness and Improves Gemcitabine Resistance by Suppressing Nuclear Factor κB Activation in Pancreatic Cancer Cell Lines |
| title_sort | natural product parthenolide inhibits both angiogenesis and invasiveness and improves gemcitabine resistance by suppressing nuclear factor κb activation in pancreatic cancer cell lines |
| topic | parthenolide pancreatic cancer gemcitabine resistance NF-κB invasion angiogenesis |
| url | https://www.mdpi.com/2072-6643/16/5/705 |
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