Deoxybouvardin-glucoside induces apoptosis in non-small cell lung cancer cells by targeting EGFR/MET and AKT signaling pathway
Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related deaths worldwide. Its treatment is complicated due to the development of resistance to conventional chemotherapy and targeted therapy. Deoxybouvardin and related cyclic hexapeptides reportedly exhibit antitumor activities, but t...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
IfADo - Leibniz Research Centre for Working Environment and Human Factors, Dortmund
2024-10-01
|
| Series: | EXCLI Journal : Experimental and Clinical Sciences |
| Subjects: | |
| Online Access: | https://www.excli.de/excli/article/view/7359 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1846143806889525248 |
|---|---|
| author | Na Yeong Lee Sang Hoon Joo A-Young Nam Seung-On Lee Goo Yoon Seung-sik Cho Yung Hyun Choi Jin Woo Park Jung-Hyun Shim |
| author_facet | Na Yeong Lee Sang Hoon Joo A-Young Nam Seung-On Lee Goo Yoon Seung-sik Cho Yung Hyun Choi Jin Woo Park Jung-Hyun Shim |
| author_sort | Na Yeong Lee |
| collection | DOAJ |
| description | Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related deaths worldwide. Its treatment is complicated due to the development of resistance to conventional chemotherapy and targeted therapy. Deoxybouvardin and related cyclic hexapeptides reportedly exhibit antitumor activities, but their mechanisms of action remain unclear. This study aimed to investigate the anticancer mechanisms of deoxybouvardin glucoside (DBG), a glucosidic form of deoxybouvardin from Rubia species, in gefitinib (GEF)-sensitive and -resistant NSCLC HCC827 cells. The effects of DBG treatment on cell proliferation were evaluated using a viability assay. The inhibitory effects of DBG treatment on the activities and phosphorylation of the protein kinases epidermal growth factor receptor (EGFR), MET, and AKTs were assessed using in vitro kinase assay and western blot, respectively. DBG treatment inhibited the growth of HCC827 cells in a concentration- and time-dependent manner. Results of in vitro kinase assay and western blotting showed that DBG treatment significantly inhibited the activities and phosphorylation of the protein kinases EGFR, MET, and AKT. Prediction using molecular docking showed that DBG is located in the ATP-binding pockets of these kinases, supporting the kinase inhibition by DBG treatment. Moreover, DBG treatment induced reactive oxygen species (ROS) generation and cell cycle arrest in the cells. The induction of apoptosis by DBG through caspase activation was confirmed by Z-VAD-FMK treatment. In summary, DBG treatment inhibited the growth of GEF-sensitive and -resistant NSCLC cells by targeting EGFR, MET, and AKTs. Moreover, it induced apoptosis by inducing ROS generation and caspase activation. These results indicate that DBG is a potential therapeutic agent for the treatment of GEF-resistant NSCLC. |
| format | Article |
| id | doaj-art-a2f044b6fa1446ff9c60f27c29629e5c |
| institution | Kabale University |
| issn | 1611-2156 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | IfADo - Leibniz Research Centre for Working Environment and Human Factors, Dortmund |
| record_format | Article |
| series | EXCLI Journal : Experimental and Clinical Sciences |
| spelling | doaj-art-a2f044b6fa1446ff9c60f27c29629e5c2024-12-02T10:14:54ZengIfADo - Leibniz Research Centre for Working Environment and Human Factors, DortmundEXCLI Journal : Experimental and Clinical Sciences1611-21562024-10-01231287130210.17179/excli2024-73596798Deoxybouvardin-glucoside induces apoptosis in non-small cell lung cancer cells by targeting EGFR/MET and AKT signaling pathwayNa Yeong Lee0https://orcid.org/0000-0003-2681-3344Sang Hoon Joo1https://orcid.org/0000-0001-8660-884XA-Young Nam2https://orcid.org/0000-0003-0162-108XSeung-On Lee3https://orcid.org/0000-0003-1293-4604Goo Yoon4https://orcid.org/0000-0001-7998-4708Seung-sik Cho5https://orcid.org/0000-0003-1497-0529Yung Hyun Choi6https://orcid.org/0000-0002-1454-3124Jin Woo Park7https://orcid.org/0000-0002-0001-7043Jung-Hyun Shim8https://orcid.org/0000-0002-4062-4016Department of Biomedicine, Health & Life Convergence Sciences, BK21 Four, College of Pharmacy, Mokpo National University, Muan 58554, Republic of KoreaCollege of Pharmacy, Daegu Catholic University, Gyeongsan 38430, Republic of KoreaDepartment of Biomedicine, Health & Life Convergence Sciences, BK21 Four, College of Pharmacy, Mokpo National University, Muan 58554, Republic of KoreaDepartment of Biomedicine, Health & Life Convergence Sciences, BK21 Four, College of Pharmacy, Mokpo National University, Muan 58554, Republic of KoreaDepartment of Pharmacy, College of Pharmacy, Mokpo National University, Muan 58554, Republic of KoreaDepartment of Biomedicine, Health & Life Convergence Sciences, BK21 Four, College of Pharmacy, Mokpo National University, Muan 58554, Republic of Korea; Department of Pharmacy, College of Pharmacy, Mokpo National University, Muan 58554, Republic of KoreaDepartment of Biochemistry, College of Korean Medicine, Dong-Eui University, Busan 47227, Republic of KoreaDepartment of Biomedicine, Health & Life Convergence Sciences, BK21 Four, College of Pharmacy, Mokpo National University, Muan 58554, Republic of Korea, Tel: +82-61-450-2704, E-mail: jwpark@mokpo.ac.krDepartment of Biomedicine, Health & Life Convergence Sciences, BK21 Four, College of Pharmacy, Mokpo National University, Muan 58554, Republic of Korea, Tel: +82-61-450-2684, E-mail: s1004jh@gmail.comNon-small cell lung cancer (NSCLC) is a leading cause of cancer-related deaths worldwide. Its treatment is complicated due to the development of resistance to conventional chemotherapy and targeted therapy. Deoxybouvardin and related cyclic hexapeptides reportedly exhibit antitumor activities, but their mechanisms of action remain unclear. This study aimed to investigate the anticancer mechanisms of deoxybouvardin glucoside (DBG), a glucosidic form of deoxybouvardin from Rubia species, in gefitinib (GEF)-sensitive and -resistant NSCLC HCC827 cells. The effects of DBG treatment on cell proliferation were evaluated using a viability assay. The inhibitory effects of DBG treatment on the activities and phosphorylation of the protein kinases epidermal growth factor receptor (EGFR), MET, and AKTs were assessed using in vitro kinase assay and western blot, respectively. DBG treatment inhibited the growth of HCC827 cells in a concentration- and time-dependent manner. Results of in vitro kinase assay and western blotting showed that DBG treatment significantly inhibited the activities and phosphorylation of the protein kinases EGFR, MET, and AKT. Prediction using molecular docking showed that DBG is located in the ATP-binding pockets of these kinases, supporting the kinase inhibition by DBG treatment. Moreover, DBG treatment induced reactive oxygen species (ROS) generation and cell cycle arrest in the cells. The induction of apoptosis by DBG through caspase activation was confirmed by Z-VAD-FMK treatment. In summary, DBG treatment inhibited the growth of GEF-sensitive and -resistant NSCLC cells by targeting EGFR, MET, and AKTs. Moreover, it induced apoptosis by inducing ROS generation and caspase activation. These results indicate that DBG is a potential therapeutic agent for the treatment of GEF-resistant NSCLC.https://www.excli.de/excli/article/view/7359deoxybouvardin glucosidenon-small cell lung canceregfr/met/aktcell cyclereactive oxygen speciesapoptosis |
| spellingShingle | Na Yeong Lee Sang Hoon Joo A-Young Nam Seung-On Lee Goo Yoon Seung-sik Cho Yung Hyun Choi Jin Woo Park Jung-Hyun Shim Deoxybouvardin-glucoside induces apoptosis in non-small cell lung cancer cells by targeting EGFR/MET and AKT signaling pathway EXCLI Journal : Experimental and Clinical Sciences deoxybouvardin glucoside non-small cell lung cancer egfr/met/akt cell cycle reactive oxygen species apoptosis |
| title | Deoxybouvardin-glucoside induces apoptosis in non-small cell lung cancer cells by targeting EGFR/MET and AKT signaling pathway |
| title_full | Deoxybouvardin-glucoside induces apoptosis in non-small cell lung cancer cells by targeting EGFR/MET and AKT signaling pathway |
| title_fullStr | Deoxybouvardin-glucoside induces apoptosis in non-small cell lung cancer cells by targeting EGFR/MET and AKT signaling pathway |
| title_full_unstemmed | Deoxybouvardin-glucoside induces apoptosis in non-small cell lung cancer cells by targeting EGFR/MET and AKT signaling pathway |
| title_short | Deoxybouvardin-glucoside induces apoptosis in non-small cell lung cancer cells by targeting EGFR/MET and AKT signaling pathway |
| title_sort | deoxybouvardin glucoside induces apoptosis in non small cell lung cancer cells by targeting egfr met and akt signaling pathway |
| topic | deoxybouvardin glucoside non-small cell lung cancer egfr/met/akt cell cycle reactive oxygen species apoptosis |
| url | https://www.excli.de/excli/article/view/7359 |
| work_keys_str_mv | AT nayeonglee deoxybouvardinglucosideinducesapoptosisinnonsmallcelllungcancercellsbytargetingegfrmetandaktsignalingpathway AT sanghoonjoo deoxybouvardinglucosideinducesapoptosisinnonsmallcelllungcancercellsbytargetingegfrmetandaktsignalingpathway AT ayoungnam deoxybouvardinglucosideinducesapoptosisinnonsmallcelllungcancercellsbytargetingegfrmetandaktsignalingpathway AT seungonlee deoxybouvardinglucosideinducesapoptosisinnonsmallcelllungcancercellsbytargetingegfrmetandaktsignalingpathway AT gooyoon deoxybouvardinglucosideinducesapoptosisinnonsmallcelllungcancercellsbytargetingegfrmetandaktsignalingpathway AT seungsikcho deoxybouvardinglucosideinducesapoptosisinnonsmallcelllungcancercellsbytargetingegfrmetandaktsignalingpathway AT yunghyunchoi deoxybouvardinglucosideinducesapoptosisinnonsmallcelllungcancercellsbytargetingegfrmetandaktsignalingpathway AT jinwoopark deoxybouvardinglucosideinducesapoptosisinnonsmallcelllungcancercellsbytargetingegfrmetandaktsignalingpathway AT junghyunshim deoxybouvardinglucosideinducesapoptosisinnonsmallcelllungcancercellsbytargetingegfrmetandaktsignalingpathway |