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Safety of herbal medicine use during chemotherapy in patients with ovarian cancer: a “bedside-to-bench” approach

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Abstract

In this study, we explored herbal supplements used by patients during chemotherapy and test for herb-drug interactions and response of cancer cells to treatment. Patients with gynecological cancer referred to a complementary and integrative medicine (CIM) service were asked about their use of herbal medicine during chemotherapy. The leading five clinically relevant herbs selected for cytotoxicity analysis included the following: wheatgrass (Triticum aestivum), European mistletoe (Viscum album), ginger (Zingiber officinale), Ephedra (Ephedra campylopoda), and Oriental mistletoe (Viscum cruciatum). Cytotoxicity was examined using XTT assays in cisplatin-sensitive and resistant ovarian cancer cell lines (A2780, A2780CisR), and non-cancer kidney cells (HEK-293). The effect of the selected herbs on carboplatin and paclitaxel cytotoxicity was tested as well. Pro-apoptotic effects were tested using Poly(ADP-ribose) polymerase (PARP) cleavage. Of 98 patients referred to the CIM service, 42 (42.9%) reported using/intending to use herbal products during chemotherapy. European mistletoe and ginger exhibited significant anti-cancer activity in cisplatin-sensitive and resistant ovarian cells. Wheatgrass and ephedra reduced cytotoxicity of carboplatin on cisplatin-sensitive ovarian cancer cells, while ginger, European and Oriental mistletoe increased chemosensitivity in both cancer cell lines. Wheatgrass, European mistletoe, and ginger increased sensitivity to cisplatin-resistant cells treated with carboplatin and paclitaxel. No effect was observed with the addition of any of the herbs on non-cancerous embryonic kidney cells (HEK-293). Herbal medicine use by patients with ovarian cancer may influence anti-cancer activity of chemotherapy. Integrative physicians can provide “bedside-to-bench” guidance on the safety of these products.

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Acknowledgements

We would like to thank the Israel Cancer Association for supporting our research (research Grant 20150892). We would also like to thank the Galilee Biomedical Research Administration for providing partial funding to JM. We thanks Mr. Sharon Kotzer (Bara herbs) for supplying the ginger extracts; Arka Stamper for supplying wheatgrass; Eli Ben-Arye for identifying and harvesting Oriental mistletoe; and Dr. Samuelov Pharmacies Ltd for supplying Iscador preparation.

Authors contribution

Prof. Eran Ben-Arye contributed to conception and design of the study, acquisition of the data, analysis and interpretation of the data, drafting the article and revising it critically for important content, and final approval of the version to be submitted. Prof. Ofer Lavie and Dr. Elad Schiff helped in conception and design of the study, drafting the article and revising it critically for important content, and final approval of the version to be submitted. Dr. Hazem Khamaisie contributed to analysis and interpretation of the data, drafting the article and revising it critically for important content, and final approval of the version to be submitted. Dr. Orit Gressel Raz and Prof. Jamal Mahajna helped in conception and design of the study, analysis and interpretation of the data, drafting the article and revising it critically for important content, and final approval of the version to be submitted.

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    Authors and Affiliations

    1. Integrative Oncology Program, Oncology Service, Lin Medical Center, Clalit Health Services, 35 Rothschild St., Haifa and Western Galilee District, Israel

      Eran Ben-Arye, Noah Samuels & Orit Gressel Raz

    2. Complementary and Traditional Medicine Unit, Department of Family Medicine, Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel

      Eran Ben-Arye

    3. Gynecological Oncology Unit, Department of Obstetrics and Gynecology, Gynecologic Oncology Service, Carmel Medical Center, Haifa, Israel

      Ofer Lavie

    4. Tal Center for Integrative Oncology, Institute of Oncology, Sheba Medical Center, Tel Hashomer, Israel

      Noah Samuels

    5. Cancer Drug Discovery Program, Galilee Technology Center (Migal), Kiryat Shmona, Israel

      Hazem Khamaisie & Jamal Mahajna

    6. Departments of Internal Medicine and Integrative Surgery Service, Bnai Zion Hospital, Haifa, Israel

      Elad Schiff

    7. Nutritional Sciences Department, Tel Hai College, Kiryat Shmona, Israel

      Jamal Mahajna

    Authors
    1. Eran Ben-Arye
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    Correspondence to Eran Ben-Arye.

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    The authors declare that they have no conflict of interest.

    Ethical approval

    All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study protocol received the approval of the Ethics Review Board (Helsinki Committee) at the Carmel Medical Center, Haifa (ClinicalTrials.gov identification No.: NCT01860365).

    Human and animal rights

    This article does not contain any studies with animals performed by any of the authors.

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    Informed consent was obtained from all individual participants included in the study.

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    Eran Ben-Arye and Ofer Lavie should be regarded as co-first authors based on their equal contribution to the research.

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    Cite this article

    Ben-Arye, E., Lavie, O., Samuels, N. et al. Safety of herbal medicine use during chemotherapy in patients with ovarian cancer: a “bedside-to-bench” approach. Med Oncol 34, 54 (2017). https://doi.org/10.1007/s12032-017-0910-9

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    • DOI: https://doi.org/10.1007/s12032-017-0910-9

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