Article

Boswellic acid acetate induces apoptosis through caspase-mediated pathways in myeloid leukemia cells.

Division of Hematology/Oncology, Department of Medicine, Box 1178, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029-6547. .
Molecular Cancer Therapeutics (Impact Factor: 6.11). 04/2005; 4(3):381-8. DOI: 10.1158/1535-7163.MCT-03-0266
Source: PubMed

ABSTRACT The mechanism of the cytotoxic effect of boswellic acid acetate, a 1:1 mixture of alpha-boswellic acid acetate and beta-boswellic acid acetate, isolated from Boswellia carterri Birdw on myeloid leukemia cells was investigated in six human myeloid leukemia cell lines (NB4, SKNO-1, K562, U937, ML-1, and HL-60 cells). Morphologic and DNA fragmentation assays indicated that the cytotoxic effect of boswellic acid acetate was mediated by induction of apoptosis. More than 50% of the cells underwent apoptosis after treatment with 20 mug/mL boswellic acid for 24 hours. This apoptotic process was p53 independent. The levels of apoptosis-related proteins Bcl-2, Bax, and Bcl-XL were not modulated by boswellic acid acetate. Boswellic acid acetate induced Bid cleavage and decreased mitochondrial membrane potential without production of hydrogen peroxide. A general caspase inhibitor (Z-VAD-FMK) and a specific caspase-8 inhibitor II (Z-IETD-FMK) blocked boswellic acid acetate-induced apoptosis. The mRNAs of death receptors 4 and 5 (DR4 and DR5) were induced in leukemia cells undergoing apoptosis after boswellic acid acetate treatment. These data taken together suggest that boswellic acid acetate induces myeloid leukemia cell apoptosis through activation of caspase-8 by induced expression of DR4 and DR5, and that the activated caspase-8 either directly activates caspase-3 by cleavage or indirectly by cleaving Bid, which in turn decreases mitochondria membrane potential.

0 Bookmarks
 · 
106 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The study investigated the growth-inhibiting and apoptosis mediating effects of B. serrata extract as monotherapy and combination therapy with DOX against hepatocellular carcinoma cell lines. Boswellic acid rich fraction of B. serrata extract was prepared. MTT assay on HepG2 and Hep3B cells was carried out using B. serrata alone and in combination with DOX. Further, caspase-3 activity, TNF-α level, and IL-6 level were estimated. Isobolographic analysis was carried out to evaluate the effect of combination therapy. Additionally, protective effect of B. serrata extract on DOX induced hepatic toxicity was also evaluated in Wistar rats. B. serrata extract inhibited growth of HepG2 (IC50 value of 21.21 ± 0.92 μg/mL) as well as HepG2 (IC50 value of 18.65 ± 0.71 μg/mL). DOX inhibited growth in HepG2 and Hep3B cells with an IC50 of 1.06 ± 0.04 μg/mL and 1.92 ± 0.09 μg/mL. Isobolographic analysis showed combination index (CI) of DOX and B. serrata extract of 0.53 ± 0.03 to 0.79 ± 0.02 suggesting synergistic behavior against the two cell lines. B. serrata extract also caused dose dependent increase in caspase-3 activity, TNF-α level, and IL-6 level which was higher (P < 0.001) with DOX (1 μM) and B. serrata extract (20 μg/mL) combination. B. serrata extract also protected Wistar rats against DOX induced hepatic toxicity.
    BioMed Research International 01/2014; · 2.71 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Frankincense ( Rǔ Xiāng; Boswellia Species), the resinous extract from the trees of the genus Boswellia, has been used for centuries in cultural ceremonies, as a cosmetic agent, and as a traditional medicine to treat a variety of ailments, especially inflammatory diseases including asthma, arthritis, cerebral edema, chronic pain syndrome, chronic bowel diseases, cancer, and some other illnesses. Boswellic acids are the active compounds of frankincense and AKBA (3-O-acetyl-11-keto-β-boswellic acid) is the most important and effective acid among them. Some studies have shown that the use of frankincense can also improve the learning and enhance the memory in animals and human beings. It seems that frankincense might have a potential ability to be used as an alternative natural medicine not only for chronic and inflammatory diseases but also for brain and memory disorders.
    Journal of traditional and complementary medicine. 01/2013; 3(4):221-226.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Introduction Basal-cell carcinoma (BCC) is the most common form of skin cancer. Incidence of BCC is rising rapidly worldwide associated with a significant increase in health care costs. Various treatment options are available for patients diagnosed with BCC ranging from surgery, electrodessication, radiation, photodynamic therapy to non-invasive therapeutic approaches. Traditionally being used for aromatherapy, based on the abundance of highly volatile, aromatic compounds, frankincense essential oil prepared by hydrodistillation of Boswellia sacra gum resins, also possesses anti-cancer activity that can potentially provide non-surgical and non-invasive treatment option for BCC by topical application. This case report discusses the management of BCC of the skin using frankincense (Boswellia sacra) essential oil. Case report We present a case of a male patient, with two foci (arm and chest) of BCC, treated with local and topical application of frankincense essential oil several times a day, for a period of 20 weeks. Biopsies were performed before and after frankincense essential oil treatment. Pathological study demonstrated total resolution of the BCC on the arm and substantial resolution in the BCC of the chest after treatment. Significant increase in apoptotic cells was observed in the residual carcinoma in the chest. Topical application of frankincense essential oil did not cause redness, swelling, erosion, crusts, vesicles, squamae, itching, tingling, or any other local or systemic side effects in this patient. Conclusion Local application of frankincense essential oil may provide a non-surgical treatment alternative, with no or minimal side effect for carcinoma in situ, minimally invasive carcinoma and pre-cancerous conditions such as actinic keratosis. A study with larger number of patients with both squamous-cell carcinoma and BCC is required to confirm our current findings.
    OA Publishing London. 01/2013;