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Magnolol induces apoptosis via caspase-independent pathways in non-small cell lung cancer cells

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Abstract

Magnolol, a hydroxylated biphenyl agent isolated from herbal planet Magnolia officinalis, is a component of traditional Asian herbal teas. It has been reported to have anti-microbial, anti-inflammatory, and anti-cancer activity. Non-small cell lung cancer (NSCLC) cell lines (A549, H441 and H520) and normal human bronchial epithelial cells (HBECs) were used to evaluate the cytotoxic effect of magnolol. We show that magnolol inhibited cellular proliferation, increased DNA fragmentation, and decreased mitochondrial membrane potential in all NSCLC cells, but had no cytotoxic effect on HBECs. Magnolol triggered the release of pro-apoptotic proteins: Bid, Bax and cytochrome c from mitochondria, but did not activate the caspase-3, -8, and -9, suggesting that magnolol induces apoptosis of NSCLC cell lines via a caspase-independent pathway. The caspase-independent pathway is mediated through the activation of nuclear translocation of apoptosis-inducing factor, endonuclease G and cleaved poly(ADP-ribose) polymerase, which played important roles in mediating cell death. Furthermore, magnolol inhibited PI3K/AKT and ERK1/2 activity, but up-regulated p38 and JNK activity in A549 cell lines. The results of this study provided a basis for understanding and developing magnolol as a novel treatment of NSCLC.

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Acknowledgments

This study was supported in part by the Grants KMUH9-9M63 and KMUH9-9M64 from Kaohsiung Medical University, the Grants NSC 100-2320-B-037-009, NSC 99-2221-E-037-006-MY3 and NSC 102-2320-B-039-025 from National Science Council, and Grant DOH102-TD-B-111-004 from Taiwan Department of Health Clinical Trial and Research Center of Excellence.

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The authors declare they have no conflict of interest.

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Authors and Affiliations

  1. Department of Respiratory Therapy, College of Medicine, Kaohsiung Medical University, No. 100, Shih-Chuan 1st Road, Kao-hsiung, 80708, Taiwan

    Jong-Rung Tsai, Inn-Wen Chong, Jhi-Jhu Hwang, Shah-Hwa Chou & Po-Len Liu

  2. Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kao-hsiung, Taiwan

    Jong-Rung Tsai, Inn-Wen Chong & Jhi-Jhu Hwang

  3. Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan

    Yung-Hsiang Chen

  4. Department of Medical Research, China Medical University Hospital, Taichung, Taiwan

    Yung-Hsiang Chen

  5. Division of Cardiology, Faculty of Medicine, Cheng-Hsin General Hospital, Taipei, Taiwan

    Wei-Hsian Yin

  6. Cardiovascular Research Centre, School of Medicine, National Yang-Ming University, Taipei, Taiwan

    Wei-Hsian Yin

  7. Department of Pediatrics, Kaohsiung Medical University, Kao-hsiung, Taiwan

    Hsiu-Lin Chen

  8. Division of Chest Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kao-hsiung, Taiwan

    Shah-Hwa Chou

  9. Department of Biotechnology, Kaohsiung Medical University, Kao-hsiung, Taiwan

    Chien-Chih Chiu

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  1. Jong-Rung Tsai
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  9. Po-Len Liu
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Correspondence to Po-Len Liu.

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Tsai, JR., Chong, IW., Chen, YH. et al. Magnolol induces apoptosis via caspase-independent pathways in non-small cell lung cancer cells. Arch. Pharm. Res. 37, 548–557 (2014). https://doi.org/10.1007/s12272-013-0232-1

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