dioscorealide-b and Breast-Neoplasms

Dioscorealide B is an active compound from the rhizome of Dioscorea membranacea Pierre which locally known as "Hua-Khao-Yen". This medicinal plant has long been used in the anticancer prescription of Thai traditional medicine.. To examine the cytotoxic effect and mechanism of Dioscorealide B in human breast carcinoma cells.. Dioscorealide B was isolated from the rhizome of Hua KhaoYen (Dioscorea membranacea).The cytotoxicity of Dioscorealide B was evaluated in two human breast cancer cell lines, MCF-7 and MDA-MB 468 by Sulphorhodamine B (SRB) assay. RT-PCR and Caspase-Glo assay were used to further elucidate its cytotoxic mechanism.. Dioscorealide B showed cytotoxic effect on MCF-7 (IC50 = 2.76 microM) and MDA-MB 468 (IC50 = 9.93 microM). The mRNA level for p53, p21 and Bax were increased while Bcl-2 was decreased after the treatment. MCF-7 treated with Dioscorealide B showed the induction of apoptosis via the activation of caspase-9 and -7.. The results suggested that the mechanisms of Dioscorealide B might be involved in p53 and the intrinsic apoptotic pathway.

Topics: Apoptosis; Breast Neoplasms; Cell Line, Tumor; Dioscorea; Heterocyclic Compounds, 4 or More Rings; Humans; Inhibitory Concentration 50; Plant Extracts; Plants, Medicinal; Reverse Transcriptase Polymerase Chain Reaction; Rhizome; Thailand

Dioscorealide B is a pharmacologically active compound from the rhizome of the Thai medicinal plant Dioscorea membranacea. Here, we demonstrated that in vitro treatment of dioscorealide B resulted in a cytotoxic effect on MCF-7 human breast cancer cells (IC50 = 2.82 microM). To determine whether this compound induces apoptosis in MCF-7, the Annexin V assay was performed. The data showed that the number of apoptotic cells were increased 7-12 folds over that of the control cells after treatment with various concentrations of dioscorealide B (3, 6 and 12 microM) for 24 hours. Dioscorealide B-induced apoptosis was associated with modulation of the multidomain Bcl-2 family members Bax, Bak and Bcl-2. After treatment with 3 microM dioscorealide B, acceleration of the level of proapoptotic proteins Bax and Bak were observed at 6 hours and 12 hours, respectively, while the decrease in the expression of antiapoptotic protein Bcl-2 was observed 3 hours after the treatment. These effects of dioscorealide B might result in the activation of caspase-8, -9 and -7, which lead to apoptosis in MCF-7 cells. Taken together, the results of this study provide evidence that dioscorealide B possesses an antitumor property against human breast cancer cells and thus provide the molecular basis for the further development of dioscorealide B as a novel chemotherapeutic agent for breast cancer treatment.

Topics: Apoptosis; bcl-2 Homologous Antagonist-Killer Protein; bcl-2-Associated X Protein; Breast Neoplasms; Caspase 8; Cell Line, Tumor; Female; Heterocyclic Compounds, 4 or More Rings; Humans; Plants, Medicinal; Proto-Oncogene Proteins c-bcl-2; Thailand