Isoalantolactone suppresses gallbladder cancer progression via inhibiting the ERK signalling pathway
AbstractContext Gallbladder cancer (GBC) is the most common malignant tumour of the biliary tract. Isoalantolactone (IAL), an active sesquiterpene lactone compound isolated from the roots of Inula helenium L. (Asteraceae), has antitumour effects.Objective This study investigates the effects of IAL o...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2023-12-01
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| Series: | Pharmaceutical Biology |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/13880209.2023.2191645 |
| _version_ | 1827302093949501440 |
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| author | Xingyu Lv Yuqi Lin Xi Zhu Xiujun Cai |
| author_facet | Xingyu Lv Yuqi Lin Xi Zhu Xiujun Cai |
| author_sort | Xingyu Lv |
| collection | DOAJ |
| description | AbstractContext Gallbladder cancer (GBC) is the most common malignant tumour of the biliary tract. Isoalantolactone (IAL), an active sesquiterpene lactone compound isolated from the roots of Inula helenium L. (Asteraceae), has antitumour effects.Objective This study investigates the effects of IAL on GBC.Materials and methods In vitro, NOZ and GBC-SD cells were treated with IAL (0, 10, 20 and 40 μM) for 24 h. The DMSO-treated cells were selected as a control. Cell proliferation, migration, invasion and apoptosis were measured by the CCK-8 assay, transwell assay, flow cytometry and western blot. In vivo, subcutaneous tumour xenografts were constructed by injecting nude mice (BALB/C) with 5 × 106 NOZ cells. Mice were divided into the control group (equal amount of DMSO), the IAL group (10 mg/kg/day) and the IAL + Ro 67-7476 group (IAL, 10 mg/kg/day; Ro 67-7476, 4 mg/kg/day). The study duration was 30 days.Results Compared with the DMSO group, cell proliferation of NOZ (IC50 15.98 μM) and GBC-SD (IC50 20.22 μM) was inhibited by about 70% in the IAL 40 μM group. Migration and invasion were suppressed by about 80%. Cell apoptosis rate was increased about three-fold. The phosphorylation level of ERK was decreased to 30–35%. Tumour volume and weight (about 80% reduction) were suppressed by IAL in vivo. Moreover, the effects of IAL were abolished by Ro 67-7476 in vitro and in vivo.Discussion and conclusions Our findings indicate that IAL could inhibit GBC progression in vitro and in vivo by inhibiting the ERK signalling pathway. |
| first_indexed | 2024-03-09T00:09:22Z |
| format | Article |
| id | doaj.art-92417d74df3c422eaef8baec3658f08d |
| institution | Directory Open Access Journal |
| issn | 1388-0209 1744-5116 |
| language | English |
| last_indexed | 2024-04-24T16:38:34Z |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Pharmaceutical Biology |
| spelling | doaj.art-92417d74df3c422eaef8baec3658f08d2024-03-29T11:10:26ZengTaylor & Francis GroupPharmaceutical Biology1388-02091744-51162023-12-0161155656710.1080/13880209.2023.2191645Isoalantolactone suppresses gallbladder cancer progression via inhibiting the ERK signalling pathwayXingyu Lv0Yuqi Lin1Xi Zhu2Xiujun Cai3Department of General Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of General Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of General Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of General Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaAbstractContext Gallbladder cancer (GBC) is the most common malignant tumour of the biliary tract. Isoalantolactone (IAL), an active sesquiterpene lactone compound isolated from the roots of Inula helenium L. (Asteraceae), has antitumour effects.Objective This study investigates the effects of IAL on GBC.Materials and methods In vitro, NOZ and GBC-SD cells were treated with IAL (0, 10, 20 and 40 μM) for 24 h. The DMSO-treated cells were selected as a control. Cell proliferation, migration, invasion and apoptosis were measured by the CCK-8 assay, transwell assay, flow cytometry and western blot. In vivo, subcutaneous tumour xenografts were constructed by injecting nude mice (BALB/C) with 5 × 106 NOZ cells. Mice were divided into the control group (equal amount of DMSO), the IAL group (10 mg/kg/day) and the IAL + Ro 67-7476 group (IAL, 10 mg/kg/day; Ro 67-7476, 4 mg/kg/day). The study duration was 30 days.Results Compared with the DMSO group, cell proliferation of NOZ (IC50 15.98 μM) and GBC-SD (IC50 20.22 μM) was inhibited by about 70% in the IAL 40 μM group. Migration and invasion were suppressed by about 80%. Cell apoptosis rate was increased about three-fold. The phosphorylation level of ERK was decreased to 30–35%. Tumour volume and weight (about 80% reduction) were suppressed by IAL in vivo. Moreover, the effects of IAL were abolished by Ro 67-7476 in vitro and in vivo.Discussion and conclusions Our findings indicate that IAL could inhibit GBC progression in vitro and in vivo by inhibiting the ERK signalling pathway.https://www.tandfonline.com/doi/10.1080/13880209.2023.2191645IALtraditional Chinese medicineantitumour drugRo 67-7476MAPK |
| spellingShingle | Xingyu Lv Yuqi Lin Xi Zhu Xiujun Cai Isoalantolactone suppresses gallbladder cancer progression via inhibiting the ERK signalling pathway Pharmaceutical Biology IAL traditional Chinese medicine antitumour drug Ro 67-7476 MAPK |
| title | Isoalantolactone suppresses gallbladder cancer progression via inhibiting the ERK signalling pathway |
| title_full | Isoalantolactone suppresses gallbladder cancer progression via inhibiting the ERK signalling pathway |
| title_fullStr | Isoalantolactone suppresses gallbladder cancer progression via inhibiting the ERK signalling pathway |
| title_full_unstemmed | Isoalantolactone suppresses gallbladder cancer progression via inhibiting the ERK signalling pathway |
| title_short | Isoalantolactone suppresses gallbladder cancer progression via inhibiting the ERK signalling pathway |
| title_sort | isoalantolactone suppresses gallbladder cancer progression via inhibiting the erk signalling pathway |
| topic | IAL traditional Chinese medicine antitumour drug Ro 67-7476 MAPK |
| url | https://www.tandfonline.com/doi/10.1080/13880209.2023.2191645 |
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