Artemisia absinthium (AA): a novel potential complementary and alternative medicine for breast cancer.

forrás: https://www.ncbi.nlm.nih.gov/pubmed/22311047


2016-09-30 12:24:02


Natural products have become increasingly important in pharmaceutical discoveries, and traditional herbalism has been a pioneering specialty in biomedical science. The search for effective plant-derived anticancer agents has continued to gain momentum in recent years. The present study aimed to investigate the role of crude extracts of the aerial parts of Artemisia absinthium (AA) extract in modulating intracellular signaling mechanisms, in particular its ability to inhibit cell proliferation and promote apoptosis in a human breast carcinoma estrogenic-unresponsive cell line, MDA-MB-231, and an estrogenic-responsive cell line, MCF-7. Cells were incubated with various concentrations of AA, and anti-proliferative activity was assessed by MTT assays, fluorescence microscopy after propidium iodide staining, western blotting and cell cycle analysis. Cell survival assays indicated that AA was cytotoxic to both MDA-MB-231 and MCF-7 cells. The morphological features typical of nucleic staining and the accumulation of sub-G1 peak revealed that the extract triggered apoptosis. Treatment with 25 ÎĽg/mL AA resulted in activation of caspase-7 and upregulation of Bad in MCF-7 cells, while exposure to 20 ÎĽg/mL AA induced upregulation of Bcl-2 protein in a time-dependent response in MDA-MB-231 cells. Both MEK1/2 and ERK1/2 was inactivated in both cell lines after AA treatment in a time-dependent manner. These results suggest that AA-induced anti-proliferative effects on human breast cancer cells could possibly trigger apoptosis in both cell lines through the modulation of Bcl-2 family proteins and the MEK/ERK pathway. This might lead to its possible development as a therapeutic agent for breast cancer following further investigations.


Effects of transferrin conjugates of artemisinin and artemisinin dimer on breast cancer cell lines.

forrás: http://www.ncbi.nlm.nih.gov/pubmed/23267137


2014-03-11 14:25:19


Transferrin (Tf) conjugates of monomeric artemisinin (ART) and artemisinin dimer were synthesized. The two conjugates, ART-Tf and dimer-Tf, retained the original protein structure, and formed stable aggregates in aqueous buffer. ART-Tf induced declines in proteins involved in apoptosis (survivin), cell cycling (cyclin D1), oncogenesis (cmyelocytomatosis oncogene product (c-MYC)), and dysregulated WNT signaling (betacatenin) in both the human prostate (DU145) and breast (MCF7) cancer cell lines. Both ARTTf and dimer-Tf induced down-regulation of survivin, c-MYC and mutated human epidermal growth factor receptor-2 (ERBB2 or HER2) in the BT474 breast cancer cell line. To our knowledge, this is the first demonstration that an ART derivative can cause a decline of ERBB2 in a human cancer cell line. Potential mechanisms for the observed effects are presented. Both transferrin conjugates strongly inhibited the growth of BT474 cells in the same concentration range that the conjugates caused declines in the levels of ERBB2, survivin, and c-MYC, while showing essentially no toxicity towards MCF10A normal breast cells.


Selective cancer cell cytotoxicity from exposure to dihydroartemisinin and holotransferrin.

forrás: http://www.ncbi.nlm.nih.gov/pubmed/7750093


2014-03-11 14:21:47


Rapid cell death, as evidenced by a decrease in cell counts, was observed when molt-4-lymphoblastoid cells, a human leukemia cell line, were exposed to holotransferrin (12 microM) and dihydroartemisinin (1-200 microM). Incubation with either compound alone was significantly less effective. Significantly less cell death was observed when normal human lymphocytes were exposed to a combination of these 2 drugs. Probit analysis of doseresponse functions shows that the drug combination is approximately 100 times more effective on molt-4 cells than lymphocytes (LD50s for molt-4 and lymphocytes were 2.59 microM and 230 microM, respectively).

This drug combination may provide a novel approach for cancer treatment.


Involvement of the mitochondrial pathway and Bim/Bcl-2 balance in dihydroartemisinin-induced apoptosis in human breast cancer in vitro.

forrás: http://www.ncbi.nlm.nih.gov/pubmed/23138847


2014-03-11 14:13:24


Dihydroartemisinin (DHA), a semi-synthetic derivative and active metabolite of artemisinin, has been shown to have profound anticancer potential in addition to its strong anti-malarial activity. The purpose of the present study was to thoroughly investigate the anti-neoplastic effects induced by DHA and to provide a molecular basis for the use of DHA in the treatment of breast cancer. Our results demonstrated that DHA could significantly inhibit the cell proliferation of breast cancer in a dose- and time-dependent manner that was associated with induced apoptosis and G0/G1 cell cycle arrest, and the half maximal inhibitory concentrations (IC50) of DHA treatment were 60.03, 33.86 and 17.18 ÎĽM for 24, 48 and 72 h, respectively. Moreover, the DHA treatment dramatically increased the protein expression of caspase-8, cleaved caspase-9, activated Bid and induced the release of cytochrome c from mitochondria into the cytosol. In addition, the apoptotic action of DHA was associated with the increased expression of the pro-apoptotic gene Bim and a decreased expression of the anti-apoptotic gene Bcl-2. Therefore, the mitochondrial pathway is involved in the apoptosis of breast cancer cells induced by DHA and the imbalance of the Bim/Bcl-2 interaction may promote the beneficial effect against breast cancer cells. Overall, our study provides the scientific rationale for the clinical usage of DHA for breast cancer.


Effects of artemisinin dimers on rat breast cancer cells in vitro and in vivo.

forrás: http://www.ncbi.nlm.nih.gov/pubmed/22199268


2014-03-11 14:11:18


Artemisinin has been shown to be an effective antimalarial and anticancer compound. Dimers of artemisinin have been synthesized and shown to be potent antimalarials compared with monomers. In the present study, we investigated the effect of two artemisinin dimers (dimeralcohol and dimer-hydrazone) on rat mammary adenocarcinoma cells (MTLn3) in vitro and in vivo compared with that of the artemisinin monomer dihydroartemisinin (DHA). We found that the dimers are considerably more potent than DHA in killing MTLn3 cells in vitro and suppressing the growth of MTLn3 breast tumors in vivo.


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