Background: Regardless of the availability of therapeutic options, the overall 5-year survival for patients diagnosed\r\nwith pancreatic cancer remains less than 5%. Gum resins from Boswellia species, also known as frankincense, have\r\nbeen used as a major ingredient in Ayurvedic and Chinese medicine to treat a variety of health-related conditions.\r\nBoth frankincense chemical extracts and essential oil prepared from Boswellia species gum resins exhibit\r\nanti-neoplastic activity, and have been investigated as potential anti-cancer agents. The goals of this study are to\r\nidentify optimal condition for preparing frankincense essential oil that possesses potent anti-tumor activity, and to\r\nevaluate the activity in both cultured human pancreatic cancer cells and a xenograft mouse cancer model.\r\nMethods: Boswellia sacra gum resins were hydrodistilled at 78Ã?°C; and essential oil distillate fractions were collected\r\nat different durations (Fraction I at 0ââ?¬â??2 h, Fraction II at 8ââ?¬â??10 h, and Fraction III at 11ââ?¬â??12 h). Hydrodistillation of the\r\nsecond half of gum resins was performed at 100Ã?°C; and distillate was collected at 11ââ?¬â??12 h (Fraction IV). Chemical\r\ncompositions were identified by gas chromatographyââ?¬â??mass spectrometry (GC-MS); and total boswellic acids\r\ncontents were quantified by high-performance liquid chromatography (HPLC). Frankincense essential oil-modulated\r\npancreatic tumor cell viability and cytotoxicity were determined by colorimetric assays. Levels of apoptotic markers,\r\nsignaling molecules, and cell cycle regulators expression were characterized by Western blot analysis. A heterotopic\r\n(subcutaneous) human pancreatic cancer xenograft nude mouse model was used to evaluate anti-tumor capability\r\nof Fraction IV frankincense essential oil in vivo. Frankincense essential oil-induced tumor cytostatic and cytotoxic\r\nactivities in animals were assessed by immunohistochemistry.\r\nResults: Longer duration and higher temperature hydrodistillation produced more abundant high molecular\r\nweight compounds, including boswellic acids, in frankincense essential oil fraactions. Human pancreatic cancer cells\r\nwere sensitive to Fractions III and IV (containing higher molecular weight compounds) treatment with suppressed\r\ncell viability and increased cell death. Essential oil activated the caspase-dependent apoptotic pathway, induced a\r\nrapid and transient activation of Akt and Erk1/2, and suppressed levels of cyclin D1 cdk4 expression in cultured\r\npancreatic cancer cells. In addition, Boswellia sacra essential oil Fraction IV exhibited anti-proliferative and\r\npro-apoptotic activities against pancreatic tumors in the heterotopic xenograft mouse model.
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