Garcioligantone J and K, a pair of epimeric caged-polyprenylated xanthonoids from Garcinia Oligantha, inhibit the growth of lung cancer cells through ER stress-mediated apoptosis
Garcioligantone J and K (GLJ and GLK) are a pair of isomers isolated from Garcinia Oligantha Merr. Herein, we described the structure elucidation including the absolute configurations of GLJ and GLK, explored and compared their anti-cancerous effects and underlying mechanism in A549 and NCI-H292 ce...
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Elsevier
2025-12-01
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| Series: | Pharmaceutical Science Advances |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2773216925000030 |
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| author | Lingyu Li Hao Zheng Qingying Liu Dongmei Ren |
| author_facet | Lingyu Li Hao Zheng Qingying Liu Dongmei Ren |
| author_sort | Lingyu Li |
| collection | DOAJ |
| description | Garcioligantone J and K (GLJ and GLK) are a pair of isomers isolated from Garcinia Oligantha Merr. Herein, we described the structure elucidation including the absolute configurations of GLJ and GLK, explored and compared their anti-cancerous effects and underlying mechanism in A549 and NCI-H292 cells. The results indicated that GLJ and GLK are two isomers with different configuration at C-12, they inhibited cell proliferation and induced apoptosis in two lung cancer cell lines with almost the same extent. The induction of apoptosis by GLJ and GLK was demonstrated by DAPI and annexin-V-FITC/PI staining. Further investigation revealed increased Bax/Bcl-2 ratio, cleaved caspase-3, caspase-9 and PARP, loss of mitochondrial membrane potential (MMP) in cells, indicating that GLJ and GLK induced mitochondrial apoptosis. Increased GRP78, p-eIF2α and GADD153 manifested that endoplasmic reticulum (ER) stress was induced by GLJ and GLK. Meanwhile, upregulated reactive oxygen species (ROS) level was found and GLJ and GLK-induced ER stress and apoptosis could be attenuated by ROS scavenger NAC. Apoptosis induced by GLJ and GLK also could be alleviated by ER stress inhibitor 4-PBA. These showed that GLJ and GLK-induced apoptosis was mediated by ER stress relied on ROS generation. The efficacy of GLJ and GLK on lung cancer cell proliferation was further demonstrated in a zebrafish xenograft model. Collectively, the absolute configurations of GLJ and GLK were identified and they exerted lethal effects on lung cancer cells to the same extent via ROS-ER stress-mitochondrial apoptosis signaling, suggesting that GLJ and GLK might be used as potential modulating agents in lung cancer treatments. |
| format | Article |
| id | doaj-art-2cbeb92543ea4d208b7461df05a45e82 |
| institution | DOAJ |
| issn | 2773-2169 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Elsevier |
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| series | Pharmaceutical Science Advances |
| spelling | doaj-art-2cbeb92543ea4d208b7461df05a45e822025-08-20T03:05:07ZengElsevierPharmaceutical Science Advances2773-21692025-12-01310006510.1016/j.pscia.2025.100065Garcioligantone J and K, a pair of epimeric caged-polyprenylated xanthonoids from Garcinia Oligantha, inhibit the growth of lung cancer cells through ER stress-mediated apoptosisLingyu Li0Hao Zheng1Qingying Liu2Dongmei Ren3Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Wenhua Road, Jinan, 250012, ChinaKey Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Wenhua Road, Jinan, 250012, ChinaSchool of Pharmaceutical Sciences, Shandong Xiandai University, ChinaKey Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Wenhua Road, Jinan, 250012, China; Corresponding author.Garcioligantone J and K (GLJ and GLK) are a pair of isomers isolated from Garcinia Oligantha Merr. Herein, we described the structure elucidation including the absolute configurations of GLJ and GLK, explored and compared their anti-cancerous effects and underlying mechanism in A549 and NCI-H292 cells. The results indicated that GLJ and GLK are two isomers with different configuration at C-12, they inhibited cell proliferation and induced apoptosis in two lung cancer cell lines with almost the same extent. The induction of apoptosis by GLJ and GLK was demonstrated by DAPI and annexin-V-FITC/PI staining. Further investigation revealed increased Bax/Bcl-2 ratio, cleaved caspase-3, caspase-9 and PARP, loss of mitochondrial membrane potential (MMP) in cells, indicating that GLJ and GLK induced mitochondrial apoptosis. Increased GRP78, p-eIF2α and GADD153 manifested that endoplasmic reticulum (ER) stress was induced by GLJ and GLK. Meanwhile, upregulated reactive oxygen species (ROS) level was found and GLJ and GLK-induced ER stress and apoptosis could be attenuated by ROS scavenger NAC. Apoptosis induced by GLJ and GLK also could be alleviated by ER stress inhibitor 4-PBA. These showed that GLJ and GLK-induced apoptosis was mediated by ER stress relied on ROS generation. The efficacy of GLJ and GLK on lung cancer cell proliferation was further demonstrated in a zebrafish xenograft model. Collectively, the absolute configurations of GLJ and GLK were identified and they exerted lethal effects on lung cancer cells to the same extent via ROS-ER stress-mitochondrial apoptosis signaling, suggesting that GLJ and GLK might be used as potential modulating agents in lung cancer treatments.http://www.sciencedirect.com/science/article/pii/S2773216925000030Garcioligantone J and KApoptosisER stressROSLung cancer |
| spellingShingle | Lingyu Li Hao Zheng Qingying Liu Dongmei Ren Garcioligantone J and K, a pair of epimeric caged-polyprenylated xanthonoids from Garcinia Oligantha, inhibit the growth of lung cancer cells through ER stress-mediated apoptosis Pharmaceutical Science Advances Garcioligantone J and K Apoptosis ER stress ROS Lung cancer |
| title | Garcioligantone J and K, a pair of epimeric caged-polyprenylated xanthonoids from Garcinia Oligantha, inhibit the growth of lung cancer cells through ER stress-mediated apoptosis |
| title_full | Garcioligantone J and K, a pair of epimeric caged-polyprenylated xanthonoids from Garcinia Oligantha, inhibit the growth of lung cancer cells through ER stress-mediated apoptosis |
| title_fullStr | Garcioligantone J and K, a pair of epimeric caged-polyprenylated xanthonoids from Garcinia Oligantha, inhibit the growth of lung cancer cells through ER stress-mediated apoptosis |
| title_full_unstemmed | Garcioligantone J and K, a pair of epimeric caged-polyprenylated xanthonoids from Garcinia Oligantha, inhibit the growth of lung cancer cells through ER stress-mediated apoptosis |
| title_short | Garcioligantone J and K, a pair of epimeric caged-polyprenylated xanthonoids from Garcinia Oligantha, inhibit the growth of lung cancer cells through ER stress-mediated apoptosis |
| title_sort | garcioligantone j and k a pair of epimeric caged polyprenylated xanthonoids from garcinia oligantha inhibit the growth of lung cancer cells through er stress mediated apoptosis |
| topic | Garcioligantone J and K Apoptosis ER stress ROS Lung cancer |
| url | http://www.sciencedirect.com/science/article/pii/S2773216925000030 |
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