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Exploring the therapeutic potential of rabdoternin E in lung cancer treatment: Targeting the ROS/p38 MAPK/JNK signaling pathway

  • Authors:
    • Jinghui Jin
    • Juan Nan
    • Yanpo Si
    • Xiaohui Chen
    • Haibo Wang
    • Xiaowei Wang
    • Jingwang Huang
    • Tao Guo
  • View Affiliations / Copyright

    Affiliations: School of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, Henan 450046, P.R. China, Academy of Chinese Medical Science, Henan University of Chinese Medicine, Zhengzhou, Henan 450046, P.R. China, NMPA Key Laboratory for Quality Control of Traditional Chinese Medicine (Chinese Materia Medica and Prepared Sections), Henan Institute for Drug and Medical Device Inspection (Henan Vaccine Issuance Center), Zhengzhou, Henan 450018, P.R. China, Henan Jishi Pharmaceutical Co., Ltd., Jiyuan, Henan 459000, P.R. China
    Copyright: © Jin et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 4.0].
  • Article Number: 206
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    Published online on: September 12, 2024
       https://doi.org/10.3892/mmr.2024.13330
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Abstract

Lung cancer has the highest incidence and mortality rates of all cancer types in China and therefore represents a serious threat to human health. In the present study, the mechanism of rabdoternin E against the proliferation of the lung cancer cell line A549 was explored. It was found that rabdoternin E caused the accumulation of large amounts of reactive oxygen species (ROS), promoted cell S phase arrest by reducing the expression of CDK2 and cyclin A2, induced apoptosis by increasing the Bax/Bcl‑2 ratio and promoted the phosphorylation of proteins in the ROS/p38 MAPK/JNK signaling pathway, which is associated with apoptosis and ferroptosis. In addition, it was also found that Z‑VAD‑FMK (an apoptosis inhibitor), ferrostatin‑1 (ferroptosis inhibitor) and N‑acetylcysteine (a ROS inhibitor) could partially or greatly reverse the cytotoxicity of rabdoternin E to A549 cells. Similarly, NAC (N‑acetylcysteine) treatment notably inhibited the rabdoternin E‑stimulated p38 MAPK and JNK activation. Furthermore, in vivo experiments in mice revealed that Rabdoternin E markedly reduced tumor volume and weight and regulated the expression levels of apoptosis and ferroptosis‑related proteins (including Ki67, Bcl‑2, Bax, glutathione peroxidase 4, solute carrier family 7 member 11 and transferrin) in the tumor tissues of mice. Histopathological observation confirmed that the number of tumor cells decreased markedly after administration of rabdoternin E. Taken together, rabdoternin E induced apoptosis and ferroptosis of A549 cells by activating the ROS/p38 MAPK/JNK signaling pathway. Therefore, the results of the present study showed that rabdoternin E is not toxic to MCF‑7 cells (normal lung cells), had no significant effect on body weight and was effective and therefore may be a novel therapeutic treatment for lung cancer.
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Copy and paste a formatted citation
Spandidos Publications style
Jin J, Nan J, Si Y, Chen X, Wang H, Wang X, Huang J and Guo T: Exploring the therapeutic potential of rabdoternin E in lung cancer treatment: Targeting the ROS/p38 MAPK/JNK signaling pathway. Mol Med Rep 30: 206, 2024.
APA
Jin, J., Nan, J., Si, Y., Chen, X., Wang, H., Wang, X. ... Guo, T. (2024). Exploring the therapeutic potential of rabdoternin E in lung cancer treatment: Targeting the ROS/p38 MAPK/JNK signaling pathway. Molecular Medicine Reports, 30, 206. https://doi.org/10.3892/mmr.2024.13330
MLA
Jin, J., Nan, J., Si, Y., Chen, X., Wang, H., Wang, X., Huang, J., Guo, T."Exploring the therapeutic potential of rabdoternin E in lung cancer treatment: Targeting the ROS/p38 MAPK/JNK signaling pathway". Molecular Medicine Reports 30.5 (2024): 206.
Chicago
Jin, J., Nan, J., Si, Y., Chen, X., Wang, H., Wang, X., Huang, J., Guo, T."Exploring the therapeutic potential of rabdoternin E in lung cancer treatment: Targeting the ROS/p38 MAPK/JNK signaling pathway". Molecular Medicine Reports 30, no. 5 (2024): 206. https://doi.org/10.3892/mmr.2024.13330
Copy and paste a formatted citation
x
Spandidos Publications style
Jin J, Nan J, Si Y, Chen X, Wang H, Wang X, Huang J and Guo T: Exploring the therapeutic potential of rabdoternin E in lung cancer treatment: Targeting the ROS/p38 MAPK/JNK signaling pathway. Mol Med Rep 30: 206, 2024.
APA
Jin, J., Nan, J., Si, Y., Chen, X., Wang, H., Wang, X. ... Guo, T. (2024). Exploring the therapeutic potential of rabdoternin E in lung cancer treatment: Targeting the ROS/p38 MAPK/JNK signaling pathway. Molecular Medicine Reports, 30, 206. https://doi.org/10.3892/mmr.2024.13330
MLA
Jin, J., Nan, J., Si, Y., Chen, X., Wang, H., Wang, X., Huang, J., Guo, T."Exploring the therapeutic potential of rabdoternin E in lung cancer treatment: Targeting the ROS/p38 MAPK/JNK signaling pathway". Molecular Medicine Reports 30.5 (2024): 206.
Chicago
Jin, J., Nan, J., Si, Y., Chen, X., Wang, H., Wang, X., Huang, J., Guo, T."Exploring the therapeutic potential of rabdoternin E in lung cancer treatment: Targeting the ROS/p38 MAPK/JNK signaling pathway". Molecular Medicine Reports 30, no. 5 (2024): 206. https://doi.org/10.3892/mmr.2024.13330
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