Ascomylactam C Induces an Immunogenic Cell Death Signature via Mitochondria-Associated ER Stress in Lung Cancer and Melanoma
Ascomylactam C (AsC) is a new 13-membered-ring macrocyclic alkaloid, which was first isolated and identified in 2019 from the secondary metabolites of the mangrove endophytic fungus <i>Didymella</i> sp. CYSK-4 in the South China Sea. AsC has been found to have a broad-spectrum cytotoxic...
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MDPI AG
2023-11-01
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| Online Access: | https://www.mdpi.com/1660-3397/21/12/600 |
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| author | Yun Huang Hongmei Yan Bingzhi Zhang Ge Zhu Jianchen Yu Xuhan Xiao Wenxuan He Yan Chen Xiaoxia Gao Zhigang She Mengfeng Li Jie Yuan |
| author_facet | Yun Huang Hongmei Yan Bingzhi Zhang Ge Zhu Jianchen Yu Xuhan Xiao Wenxuan He Yan Chen Xiaoxia Gao Zhigang She Mengfeng Li Jie Yuan |
| author_sort | Yun Huang |
| collection | DOAJ |
| description | Ascomylactam C (AsC) is a new 13-membered-ring macrocyclic alkaloid, which was first isolated and identified in 2019 from the secondary metabolites of the mangrove endophytic fungus <i>Didymella</i> sp. CYSK-4 in the South China Sea. AsC has been found to have a broad-spectrum cytotoxic activity. However, the antitumor effects in vivo and mechanisms of AsC remain unclear. The aim of this study was to describe the effects of AsC on lung cancer and melanoma cells and to explore the antitumor molecular mechanism of AsC. In vitro, we used plate colony formation experiments and demonstrated the ability of AsC to inhibit low-density tumor growth. An Annexin V/PI cell apoptosis detection experiment revealed that AsC induced tumor cell apoptosis. In vivo, AsC suppressed the tumor growth of LLC and B16F10 allograft significantly in mice, and promoted the infiltration of CD4<sup>+</sup> T and CD8<sup>+</sup> T cells in tumor tissues. Mechanistically, by analyses of Western blotting, immunofluorescence and ELISA analysis, we found that AsC increased ROS formation, induced endoplasmic reticulum (ER) stress, activated the protein kinase RNA-like ER kinase (PERK)/eukaryotic translation initiation factor (eIF2α)/activating transcription factor 4 (ATF4)/C/EBP homologous protein (CHOP) signaling pathway, and induced immunogenic cell death (ICD) of tumor cells. Our results suggest that AsC may be a potentially promising antitumor drug candidate. |
| first_indexed | 2024-03-08T20:35:23Z |
| format | Article |
| id | doaj.art-ef03315990e1441da42aa5b5fc25be52 |
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| language | English |
| last_indexed | 2024-03-08T20:35:23Z |
| publishDate | 2023-11-01 |
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| series | Marine Drugs |
| spelling | doaj.art-ef03315990e1441da42aa5b5fc25be522023-12-22T14:22:16ZengMDPI AGMarine Drugs1660-33972023-11-01211260010.3390/md21120600Ascomylactam C Induces an Immunogenic Cell Death Signature via Mitochondria-Associated ER Stress in Lung Cancer and MelanomaYun Huang0Hongmei Yan1Bingzhi Zhang2Ge Zhu3Jianchen Yu4Xuhan Xiao5Wenxuan He6Yan Chen7Xiaoxia Gao8Zhigang She9Mengfeng Li10Jie Yuan11School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, ChinaSchool of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, ChinaSchool of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, ChinaKey Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou 510080, ChinaKey Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou 510080, ChinaKey Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou 510080, ChinaSchool of Life Sciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou 510006, ChinaDepartment of Traditional Chinese Medicine, School of Pharmacy, Anhui Medical University, Hefei 230032, ChinaSchool of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, ChinaSchool of Chemistry, Sun Yat-sen University, Guangzhou 510275, ChinaSchool of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, ChinaKey Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou 510080, ChinaAscomylactam C (AsC) is a new 13-membered-ring macrocyclic alkaloid, which was first isolated and identified in 2019 from the secondary metabolites of the mangrove endophytic fungus <i>Didymella</i> sp. CYSK-4 in the South China Sea. AsC has been found to have a broad-spectrum cytotoxic activity. However, the antitumor effects in vivo and mechanisms of AsC remain unclear. The aim of this study was to describe the effects of AsC on lung cancer and melanoma cells and to explore the antitumor molecular mechanism of AsC. In vitro, we used plate colony formation experiments and demonstrated the ability of AsC to inhibit low-density tumor growth. An Annexin V/PI cell apoptosis detection experiment revealed that AsC induced tumor cell apoptosis. In vivo, AsC suppressed the tumor growth of LLC and B16F10 allograft significantly in mice, and promoted the infiltration of CD4<sup>+</sup> T and CD8<sup>+</sup> T cells in tumor tissues. Mechanistically, by analyses of Western blotting, immunofluorescence and ELISA analysis, we found that AsC increased ROS formation, induced endoplasmic reticulum (ER) stress, activated the protein kinase RNA-like ER kinase (PERK)/eukaryotic translation initiation factor (eIF2α)/activating transcription factor 4 (ATF4)/C/EBP homologous protein (CHOP) signaling pathway, and induced immunogenic cell death (ICD) of tumor cells. Our results suggest that AsC may be a potentially promising antitumor drug candidate.https://www.mdpi.com/1660-3397/21/12/600ascomylactam Clung cancermelanomaendoplasmic reticulum stressoxidative stressimmunogenic cell death |
| spellingShingle | Yun Huang Hongmei Yan Bingzhi Zhang Ge Zhu Jianchen Yu Xuhan Xiao Wenxuan He Yan Chen Xiaoxia Gao Zhigang She Mengfeng Li Jie Yuan Ascomylactam C Induces an Immunogenic Cell Death Signature via Mitochondria-Associated ER Stress in Lung Cancer and Melanoma Marine Drugs ascomylactam C lung cancer melanoma endoplasmic reticulum stress oxidative stress immunogenic cell death |
| title | Ascomylactam C Induces an Immunogenic Cell Death Signature via Mitochondria-Associated ER Stress in Lung Cancer and Melanoma |
| title_full | Ascomylactam C Induces an Immunogenic Cell Death Signature via Mitochondria-Associated ER Stress in Lung Cancer and Melanoma |
| title_fullStr | Ascomylactam C Induces an Immunogenic Cell Death Signature via Mitochondria-Associated ER Stress in Lung Cancer and Melanoma |
| title_full_unstemmed | Ascomylactam C Induces an Immunogenic Cell Death Signature via Mitochondria-Associated ER Stress in Lung Cancer and Melanoma |
| title_short | Ascomylactam C Induces an Immunogenic Cell Death Signature via Mitochondria-Associated ER Stress in Lung Cancer and Melanoma |
| title_sort | ascomylactam c induces an immunogenic cell death signature via mitochondria associated er stress in lung cancer and melanoma |
| topic | ascomylactam C lung cancer melanoma endoplasmic reticulum stress oxidative stress immunogenic cell death |
| url | https://www.mdpi.com/1660-3397/21/12/600 |
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