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Propolis extracts from the northern region of Thailand suppress cancer cell growth through induction of apoptosis pathways

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Summary

The continual increase in mortality rates and number of cancer cases is a matter of serious concern in developing countries. The incorporation of natural products into classical cancer treatment approaches is a promising direction. The mechanisms of A549 and HeLa cancer cell death induction by ethanolic extracts of propolis samples from Phayao, Chiang Mai, and Nan provinces in northern Thailand were investigated in this study. The propolis extract from Chiang Mai showed the highest antioxidant activity and the greatest total phenolic content. The propolis extract from Nan also exhibited the highest total flavonoid content. The proliferation of A549 and HeLa cells grown in the presence of the propolis extracts was suppressed in a dose- and time-dependent manner. Moreover, treatment of both cancer cells with the propolis extracts showed DNA fragmentation and significantly increased the number of the apoptotic cells. On A549 cells, the extrinsic and intrinsic pathways of caspase enzymes were activated by the propolis extracts from Phayao and Chiang Mai. In the case of the propolis extract from Nan, the mechanisms involved apoptosis on the A549 cells were caspase-independent pathway. The extrinsic pathway of the caspase enzyme was triggered by all of the propolis extracts on HeLa cells. Finally, oral administration of the propolis granule produced from the propolis extract from Nan resulted in extended survival of tumour-bearing mice. Therefore, propolis extracts from the northern region of Thailand demonstrated pharmacological properties, both antioxidant and anticancer activities. From these findings, it is evident that propolis extracts can be considered as a naturally obtained agent extremely useful in cancer treatment.

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Acknowledgments

We would like to thank the Research and Researcher for Industry (RRi) of The Thailand Research Fund (Grant No. PHD56I0018), Bee Product Industry Co., Ltd. and the National Research Council of Thailand (NRCT) for the financial support. We also would like to thank Prof. Dr. André M. Lieber, University of Washington, Seattle Washington, USA for kindly suggestion, providing the cervical carcinoma cell lines (HeLa), advice on flow cytometry and animal studies. We also thank Dr. Khanittha Punturee of Division of Clinical Chemistry, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University for kindly provided lung carcinoma cell lines (A549). We would like to thank Chiang Mai University Press and Mr. Matthew Hawkins, Department of English, Faculty of Humanity and Language Institute, Chiang Mai University for proof reading of the manuscript.

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Authors and Affiliations

  1. Biotechnology, Graduate School, Chiang Mai University, Chiang Mai, Thailand, 50200

    Supakit Khacha-ananda

  2. Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand, 50200

    Khajornsak Tragoolpua

  3. Department of Biology, Faculty of Science, Chiang Mai University, Chiang Mai, Thailand, 50200

    Panuwan Chantawannakul & Yingmanee Tragoolpua

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  1. Supakit Khacha-ananda
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  2. Khajornsak Tragoolpua
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  3. Panuwan Chantawannakul
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  4. Yingmanee Tragoolpua
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Correspondence to Yingmanee Tragoolpua.

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Conflict of interest

The authors; SK, KT, PC and YT declare that they have no conflict of interest.

Funding

The work was supported by Research and Researcher for Industry (RRi) of The Thailand Research Fund (Grant No. PHD56I0018) and the National Research Council of Thailand (NRCT).

Ethical approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures about animal testing were performed according to the Animal Ethics Committees, Department of Biology, Faculty of Science, Chiang Mai University (Approved protocol No. 001/14) and the Institutional Animal Care and Use Committee (IACUC), Office of Animal Welfare, University of Washington (Approved protocol No. 3108-01).

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Khacha-ananda, S., Tragoolpua, K., Chantawannakul, P. et al. Propolis extracts from the northern region of Thailand suppress cancer cell growth through induction of apoptosis pathways. Invest New Drugs 34, 707–722 (2016). https://doi.org/10.1007/s10637-016-0392-1

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