11‐Keto‐a‐Boswellic Acid, a Novel Triterpenoid from Boswellia spp., with Cytotoxic Efficacy against Treatment‐Resistant Triple Negative Breast Cancer Cell Lines

Abstract

Triterpenoids including biologically active boswellic acids constitute about twenty percent of frankincense, the oleogum resin of Boswellia spp. trees from the Burseraceae family [1– 2]. Frankincense as well as extracts thereof have been traditionally used by folk medicines, such as Ayurveda, African, Arab, and Chinese medicine, for the treatment of fever and pain. Several clinical pilot trials provided evidence for a potential therapeutic efficacy of frankincense preparations in various chronic inflammatory diseases. Moreover, preclinical studies have demonstrated that boswellic acids may be beneficial for treatment of human cancers because they also inhibit tumor growth in different animal models. We have performed a comparative analysis of more than 40 oleogum resins from different Boswellia species grown in different geographic locations [1] and we have shown that frankincense extracts induce apoptosis in triple negative breast cancer cell lines in vitro and in vivo [1– 2]. Moreover, the cytotoxic efficacy of the extracts correlated positively with the contents of boswellic acids [2]. Boswellic acids exist as two structural isomers, α‐boswellic acids (oleanane‐type skeleton) and β‐boswellic acids (ursane‐type skeleton). In the current study, we have identified the novel oleanane‐type 11‐keto‐α‐boswellic acid (αKBA) in oleogum resins of different Boswellia species. The structure of αKBA was elucidated by 1D and 2D 1H and 13C NMR analysis. The contents of the individual boswellic acid isomers was quantified in different frankincense extracts by high performance reversed‐phase liquid chromatography coupled with tandem mass spectrometric detection (HPLC‐MS/MS) and the help of fluorinated stationary phases. We have compared the toxicities of different known boswellic acids and of the newly identified αKBA against tthe reatment‐resistant, triple negative human breast cancer cell lines MDA‐MB‐231 and CAL‐148. αKBA exhibited cytotoxic activity against the cancer cells and was less toxic to normal peripheral blood mononuclear cells (PBMC) and non‐malignant human breast epithelial cells indicating tumor selectivity. Structure‐activity‐relationship between the cytotoxic activities of different boswellic acid were analyzed. Hence, the study provides evidence for the existence of a novel biologically active boswellic acid with cytotoxic activity against triple negative human breast cancer cell lines in the oleogum resin of Boswellia spp. Additionally, it offers new clues for possible structural modifications of boswellic acids to increase their cytotoxicity against cancer cells.Support or Funding InformationThis work was supported by the Academic Center for Complementary and Integrative Medicine (AZKIM), State Ministry of Baden‐Württemberg for Sciences, Research and Arts.