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Open AccessArticle

Comparative Investigation of Frankincense Nutraceuticals: Correlation of Boswellic and Lupeolic Acid Contents with Cytokine Release Inhibition and Toxicity against Triple-Negative Breast Cancer Cells

1
Institute of Pharmacology of Natural Products and Clinical Pharmacology, Ulm University, 89081 Ulm, Germany
2
Medicinal Plants Division, Research Center, Dhofar University, Salalah 211, Oman
*
Authors to whom correspondence should be addressed.
Nutrients 2019, 11(10), 2341; https://doi.org/10.3390/nu11102341
Received: 1 September 2019 / Revised: 22 September 2019 / Accepted: 26 September 2019 / Published: 2 October 2019
(This article belongs to the Special Issue Nutraceutical, Nutrition Supplements and Human Health)
For centuries, frankincense extracts have been commonly used in traditional medicine, and more recently, in complementary medicine. Therefore, frankincense constituents such as boswellic and lupeolic acids are of considerable therapeutic interest. Sixteen frankincense nutraceuticals were characterized by high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS), revealing major differences in boswellic and lupeolic acid compositions and total contents, which varied from 0.4% to 35.7%. Frankincense nutraceuticals significantly inhibited the release of proinflammatory cytokines, such as TNF-α, IL-6, and IL-8, by LPS-stimulated peripheral blood mononuclear cells (PBMC) and whole blood. Moreover, boswellic and lupeolic acid contents correlated with TNF-α, IL-1β, IL-6, IL-8, and IL-10 inhibition. The nutraceuticals also exhibited toxicity against the human triple-negative breast cancer cell lines MDA-MB-231, MDA-MB-453, and CAL-51 in vitro. Nutraceuticals with total contents of boswellic and lupeolic acids >30% were the most active ones against MDA-MB-231 with a half maximal inhibitory concentration (IC50) ≤ 7.0 µg/mL. Moreover, a frankincense nutraceutical inhibited tumor growth and induced apoptosis in vivo in breast cancer xenografts grown on the chick chorioallantoic membrane (CAM). Among eight different boswellic and lupeolic acids tested, β-ABA exhibited the highest cytotoxicity against MDA-MB-231 with an IC50 = 5.9 µM, inhibited growth of cancer xenografts in vivo, and released proinflammatory cytokines. Its content in nutraceuticals correlated strongly with TNF-α, IL-6, and IL-8 release inhibition. View Full-Text
Keywords: frankincense; Boswellia; boswellic acid; lupeolic acid; AKBA; cytokine; breast cancer; pentacyclic triterpenic acid; triterpenoid; chorioallantoic membrane assay frankincense; Boswellia; boswellic acid; lupeolic acid; AKBA; cytokine; breast cancer; pentacyclic triterpenic acid; triterpenoid; chorioallantoic membrane assay
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MDPI and ACS Style

Schmiech, M.; Lang, S.J.; Ulrich, J.; Werner, K.; Rashan, L.J.; Syrovets, T.; Simmet, T. Comparative Investigation of Frankincense Nutraceuticals: Correlation of Boswellic and Lupeolic Acid Contents with Cytokine Release Inhibition and Toxicity against Triple-Negative Breast Cancer Cells. Nutrients 2019, 11, 2341.

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