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

Abstract

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.

Acetyl-11-keto-β-boswellic acid inhibits proliferation and induces apoptosis of gastric cancer cells through the phosphatase and tensin homolog /Akt/ cyclooxygenase-2 signaling pathway

“…Our animal experiments verified the findings of in vitro experiments. Previous research confirmed that AKBA has an anti-tumor effect in nude mice[ 2 - 4 , 33 , 42 , 43 ]. Our results indicate that the tumor size of AKBA-treated nude mice is significantly smaller compared to the control group.…”

11-Keto-α-Boswellic Acid, a Novel Triterpenoid from Boswellia spp. with Chemotaxonomic Potential and Antitumor Activity against Triple-Negative Breast Cancer Cells

“…Since the chromatographic separation of the constitutional isomers of KBAs and AKBAs with the help of C18 phases was insufficient [ 4 , 5 , 16 , 23 , 24 , 25 , 26 , 27 ], other stationary phases with varying selectivities were investigated. Here, on the basis of our previous study, a fluorinated stationary phase with pentafluorophenyl (PFP) moieties was used [ 18 ].…”

“…Initially, the oleogum resins were extracted exhaustively and analyzed by HPLC-MS/MS with a C18 column, as described previously, to obtain total contents of 11-keto-boswellic acids (KBAs) and acetyl-11-keto-boswellic acids (AKBAs), respectively [ 5 ]. The analysis with C18 stationary phases enables chromatographic separation of several boswellic acids, including respective constitutional isomers, but so far, without sufficient separation of keto-boswellic acid constitutional isomers ( Figure 5 a) [ 4 , 5 , 16 , 23 , 24 , 25 , 26 , 27 ]. However, by using a pentafluorophenyl (PFP) stationary phase and the optimized chromatographic parameters, selective analysis of the constitutional isomers of KBAs and AKBAs, i.e., α-KBA, β-KBA, α-AKBA, and β-AKBA, was achieved ( Figure 5 b).…”

A Naturally Derived Carrier for Photodynamic Treatment of Squamous Cell Carcinoma: In Vitro and In Vivo Models

“…The chorioallantoic membrane is made mainly of type IV collagen, which mimics the basement membrane of the human epithelium. CAM models have been studied to evaluate anticancer drug effects on tumor growth and invasion, including effects on melanoma and head and neck squamous cell carcinoma [ 19 , 20 , 21 , 22 , 23 , 24 ].…”