Deoxybouvardin-glucoside induces apoptosis in non-small cell lung cancer cells by targeting EGFR/MET and AKT signaling pathway

Authors

  • Na Yeong Lee Department of Biomedicine, Health & Life Convergence Sciences, BK21 Four, College of Pharmacy, Mokpo National University, Muan 58554, Republic of Korea https://orcid.org/0000-0003-2681-3344
  • Sang Hoon Joo College of Pharmacy, Daegu Catholic University, Gyeongsan 38430, Republic of Korea https://orcid.org/0000-0001-8660-884X
  • A-Young Nam Department of Biomedicine, Health & Life Convergence Sciences, BK21 Four, College of Pharmacy, Mokpo National University, Muan 58554, Republic of Korea https://orcid.org/0000-0003-0162-108X
  • Seung-On Lee Department of Biomedicine, Health & Life Convergence Sciences, BK21 Four, College of Pharmacy, Mokpo National University, Muan 58554, Republic of Korea https://orcid.org/0000-0003-1293-4604
  • Goo Yoon Department of Pharmacy, College of Pharmacy, Mokpo National University, Muan 58554, Republic of Korea https://orcid.org/0000-0001-7998-4708
  • Seung-sik Cho Department 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 Korea https://orcid.org/0000-0003-1497-0529
  • Yung Hyun Choi Department of Biochemistry, College of Korean Medicine, Dong-Eui University, Busan 47227, Republic of Korea https://orcid.org/0000-0002-1454-3124
  • Jin Woo Park Department 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.kr https://orcid.org/0000-0002-0001-7043
  • Jung-Hyun Shim Department 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.com https://orcid.org/0000-0002-4062-4016

DOI:

https://doi.org/10.17179/excli2024-7359

Keywords:

deoxybouvardin glucoside, non-small cell lung cancer, EGFR/MET/AKT, cell cycle, reactive oxygen species, apoptosis

Abstract

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.

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Published

2024-10-21

How to Cite

Lee, N. Y., Joo, S. H., Nam, A.-Y., Lee, S.-O., Yoon, G., Cho, S.- sik, … Shim, J.-H. (2024). Deoxybouvardin-glucoside induces apoptosis in non-small cell lung cancer cells by targeting EGFR/MET and AKT signaling pathway. EXCLI Journal, 23, 1287–1302. https://doi.org/10.17179/excli2024-7359

Issue

Vol. 23 (2024)

Section

Original articles

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Copyright (c) 2024 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

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