Applied Biochemistry and Biotechnology

, Volume 187, Issue 4, pp 1328–1343 | Cite as

Synergistic Anticancer Effect of a Combination of Paclitaxel and 5-Demethylnobiletin Against Lung Cancer Cell Line In Vitro and In Vivo

  • Kok-Tong Tan
  • Shiming Li
  • Yi Rong Li
  • Shih-Lung Cheng
  • Sheng-Hao LinEmail author
  • Yu-Tang TungEmail author


Lung cancer remains a highly prevalent disease and a leading cause of cancer-related deaths worldwide. Currently, exploring antitumor drugs derived from herbs used in traditional Chinese medicine is increasingly becoming an attractive area of research. Paclitaxel (PTX), a highly effective chemotherapeutic drug, is widely used for treating different cancers; however, the clinical use of PTX is dose limited because of its adverse side effects. Chemotherapeutic agents are being developed to enhance the anticancer activity of PTX, particularly for use in combination therapy. 5-Demethylnobiletin (5-DMN), a natural, active compound isolated from orange peel, has been reported to induce apoptosis in several cancer cell lines. In this study, we tested the synergistic anticancer antiproliferative effects of combinations of PTX and 5-DMN on CL1–5 lung cancer cells through the MTT and propidium iodide assays. After low-dose combination treatments (PTX and 5-DMN), a reduction in cell viability and a concomitant increase in apoptosis were observed in the CL1–5 cells. We propose that 5-DMN cooperates with PTX to induce apoptosis via the caspase pathway (by modulating caspase-3, caspase-8, and caspase-9 activities). Furthermore, we observed that the combination treatment significantly suppressed tumor growth in the nude mouse xenograft model. The results suggest that the synergistic effects of PTX and 5-DMN in lung cancer cells deserve particular attention and indicate the possibility of developing additional new strategies for treating lung cancer.


Paclitaxel 5-Demethylnobiletin Non-small cell lung cancer Apoptosis Synergistic effect 



This study was supported by grants (106-CCH-IRP-072) from Changhua Christian Hospital, Taiwan.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.


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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of SurgeryTungs’ Taichung MetroHarbor HospitalTaichungRepublic of China
  2. 2.Institute of Biomedical ScienceNational Chung-Hsing UniversityTaichungRepublic of China
  3. 3.Department of Food ScienceRutgers UniversityNew BrunswickUSA
  4. 4.Department of Internal MedicineFar Eastern Memorial HospitalTaipeiRepublic of China
  5. 5.Department of Chemical Engineering and Materials ScienceYuan Ze UniversityTaoyuanRepublic of China
  6. 6.Division of Chest Medicine, Department of Internal MedicineChanghua Christian HospitalChanghuaRepublic of China
  7. 7.Graduate Institute of Metabolism and Obesity SciencesTaipei Medical UniversityTaipeiRepublic of China

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