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Pulmonary administration of curcumin inhibits B16F10 melanoma lung metastasis and invasion in mice

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Abstract

Purpose

Curcumin is expected to have beneficial effects including an anti-cancer effect. However, its lower bioavailability is a critical concern and limits the utility of curcumin in clinical practice. In this study, we investigated whether transpulmonary delivery of curcumin is pharmacologically effective along with improving its bioavailability in mice with lung metastasis.

Methods

C57BL/6J mice were injected with B16F10 melanoma cells via their tail vein and given curcumin by pulmonary administration every other day. The lung tissue of the vehicle-treated mice on day 17 was covered by nodules of metastatic melanoma.

Results

Pulmonary curcumin administration significantly and dose-dependently protected the lung metastasis of melanoma. The phosphorylation of JNK (c-Jun NH2 terminal kinase) and HLJ1 expression levels in the lung metastatic nodules of the melanoma were significantly increased by pulmonary curcumin administration. The anti-metastatic effect of curcumin was blunted in mice injected with HLJ1 knocked-down B16F10 melanoma. Systemic bioavailability after pulmonary administration was 61-times higher than after oral administration. Additionally, the curcumin concentration in the lung tissue was sustained to a high level until 24 h after pulmonary administration.

Conclusions

This study showed the usefulness of curcumin to suppress lung metastasis of melanoma by pulmonary administration, a method that may overcome the low-bioavailability of curcumin.

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Acknowledgements

We thank Theravalues (Tokyo, Japan) for suppling theracurmin®. We thank Renee Mosi, PhD, from Edanz Group (http://www.edanzediting.com/ac) for editing a draft of this manuscript.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Author information

Author notes

  1. Michiko Horiguchi

    Present address: Division of Pediatric Hematology, Oncology, and Stem Cell Transplantation, Columbia University Medical Center, New York, USA

Authors and Affiliations

  1. Division of Clinical Pharmacology, Department of Pharmacology, School of Medicine, Jichi Medical University, Tochigi, 329-0498, Japan

    Ken Shimada, Kentaro Ushijima, Chisato Suzuki & Akio Fujimura

  2. Department of Pharmaceutics and Drug Delivery, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba, Japan

    Ken Shimada, Chisato Suzuki, Michiko Horiguchi, Tomomi Akita, Mizuki Shimamura, Junki Fujii & Chikamasa Yamashita

  3. Department of Cellular and Molecular Function Analysis, Graduate School of Medical Sciences, Kanazawa University, Ishikawa, Japan

    Hitoshi Ando

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  1. Ken Shimada
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Correspondence to Kentaro Ushijima.

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The authors declare that they have no conflicts of interest.

Ethical approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. This study does not contain any studies with human participants performed by any of the authors.

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Shimada, K., Ushijima, K., Suzuki, C. et al. Pulmonary administration of curcumin inhibits B16F10 melanoma lung metastasis and invasion in mice. Cancer Chemother Pharmacol 82, 265–273 (2018). https://doi.org/10.1007/s00280-018-3616-6

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  • DOI: https://doi.org/10.1007/s00280-018-3616-6

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