Sunitinib and Pterostilbene Combination Treatment Exerts Antitumor Effects in Gastric Cancer via Suppression of PDZD8
The use of molecular-targeted drugs in the treatment of gastric cancer is increasing. However, the variety of molecular-targeted drugs in gastric cancer is still limited, and the development of new molecular-targeted therapies is required. The effect of combining sunitinib (SUN) with pterostilbene (...
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MDPI AG
2022-04-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/7/4002 |
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| author | Yudai Hojo Shingo Kishi Shiori Mori Rina Fujiwara-Tani Takamitsu Sasaki Kiyomu Fujii Yukiko Nishiguchi Chie Nakashima Yi Luo Hisashi Shinohara Hiroki Kuniyasu |
| author_facet | Yudai Hojo Shingo Kishi Shiori Mori Rina Fujiwara-Tani Takamitsu Sasaki Kiyomu Fujii Yukiko Nishiguchi Chie Nakashima Yi Luo Hisashi Shinohara Hiroki Kuniyasu |
| author_sort | Yudai Hojo |
| collection | DOAJ |
| description | The use of molecular-targeted drugs in the treatment of gastric cancer is increasing. However, the variety of molecular-targeted drugs in gastric cancer is still limited, and the development of new molecular-targeted therapies is required. The effect of combining sunitinib (SUN) with pterostilbene (PTE) on the human gastric cancer cell lines TMK1 and MKN74 was examined in in vitro and in vivo. Compared with SUN or PTE treatment alone, cotreatment induced pronounced suppression of cell proliferation, with a marked increase in oxidative stress. SUN was associated with a significant retention of mitochondrial Fe<sup>2+</sup>. SUN-treated cells decreased expression of PDZ domain-containing protein 8 (PDZD8). Knockdown of PDZD8 in both cells induced Fe<sup>2+</sup> retention, and siPDZD8+PTE markedly suppressed cell proliferation with suppressed oxidative phosphorylation, as did the combination of SUN+PTE. In a nude mouse tumor model, a pronounced antitumor effect was observed with SUN+PTE treatment compared to SUN alone. PDZD8 may be a newly discovered off-target for SUN, and that the combined use of PTE with SUN significantly promotes antitumor activity in gastric cancer cell lines. The combined use of SUN and PTE might be a new molecular-targeted therapy for gastric cancer. |
| first_indexed | 2024-03-09T11:44:49Z |
| format | Article |
| id | doaj.art-c3ba461418544b7590c180663080c667 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T11:44:49Z |
| publishDate | 2022-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-c3ba461418544b7590c180663080c6672023-11-30T23:25:14ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-04-01237400210.3390/ijms23074002Sunitinib and Pterostilbene Combination Treatment Exerts Antitumor Effects in Gastric Cancer via Suppression of PDZD8Yudai Hojo0Shingo Kishi1Shiori Mori2Rina Fujiwara-Tani3Takamitsu Sasaki4Kiyomu Fujii5Yukiko Nishiguchi6Chie Nakashima7Yi Luo8Hisashi Shinohara9Hiroki Kuniyasu10Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Nara, JapanDepartment of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Nara, JapanDepartment of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Nara, JapanDepartment of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Nara, JapanDepartment of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Nara, JapanDepartment of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Nara, JapanDepartment of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Nara, JapanDepartment of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Nara, JapanKey Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-Innovation Center of Neuroregeneration, Nantong University, Nantong 226001, ChinaDepartment of Surgery, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya 663-8501, Hyogo, JapanDepartment of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Nara, JapanThe use of molecular-targeted drugs in the treatment of gastric cancer is increasing. However, the variety of molecular-targeted drugs in gastric cancer is still limited, and the development of new molecular-targeted therapies is required. The effect of combining sunitinib (SUN) with pterostilbene (PTE) on the human gastric cancer cell lines TMK1 and MKN74 was examined in in vitro and in vivo. Compared with SUN or PTE treatment alone, cotreatment induced pronounced suppression of cell proliferation, with a marked increase in oxidative stress. SUN was associated with a significant retention of mitochondrial Fe<sup>2+</sup>. SUN-treated cells decreased expression of PDZ domain-containing protein 8 (PDZD8). Knockdown of PDZD8 in both cells induced Fe<sup>2+</sup> retention, and siPDZD8+PTE markedly suppressed cell proliferation with suppressed oxidative phosphorylation, as did the combination of SUN+PTE. In a nude mouse tumor model, a pronounced antitumor effect was observed with SUN+PTE treatment compared to SUN alone. PDZD8 may be a newly discovered off-target for SUN, and that the combined use of PTE with SUN significantly promotes antitumor activity in gastric cancer cell lines. The combined use of SUN and PTE might be a new molecular-targeted therapy for gastric cancer.https://www.mdpi.com/1422-0067/23/7/4002sunitinibpterostilbenePDZD8mitochondriaoxidative stress |
| spellingShingle | Yudai Hojo Shingo Kishi Shiori Mori Rina Fujiwara-Tani Takamitsu Sasaki Kiyomu Fujii Yukiko Nishiguchi Chie Nakashima Yi Luo Hisashi Shinohara Hiroki Kuniyasu Sunitinib and Pterostilbene Combination Treatment Exerts Antitumor Effects in Gastric Cancer via Suppression of PDZD8 International Journal of Molecular Sciences sunitinib pterostilbene PDZD8 mitochondria oxidative stress |
| title | Sunitinib and Pterostilbene Combination Treatment Exerts Antitumor Effects in Gastric Cancer via Suppression of PDZD8 |
| title_full | Sunitinib and Pterostilbene Combination Treatment Exerts Antitumor Effects in Gastric Cancer via Suppression of PDZD8 |
| title_fullStr | Sunitinib and Pterostilbene Combination Treatment Exerts Antitumor Effects in Gastric Cancer via Suppression of PDZD8 |
| title_full_unstemmed | Sunitinib and Pterostilbene Combination Treatment Exerts Antitumor Effects in Gastric Cancer via Suppression of PDZD8 |
| title_short | Sunitinib and Pterostilbene Combination Treatment Exerts Antitumor Effects in Gastric Cancer via Suppression of PDZD8 |
| title_sort | sunitinib and pterostilbene combination treatment exerts antitumor effects in gastric cancer via suppression of pdzd8 |
| topic | sunitinib pterostilbene PDZD8 mitochondria oxidative stress |
| url | https://www.mdpi.com/1422-0067/23/7/4002 |
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