Cytotoxic effect of artocarpin on T47D cells.
In our screening projects for anticancer agents from natural resources, artocarpin [6-(3-methyl-1-butenyl)-5,2',4'-trihydroxy-3-isoprenyl-7-methoxyflavone] isolated from wood of jack fruit (Artocarpus heterophyllus) showed potent cytotoxic activity on human T47D breast cancer cells. The mode of action of artocarpin was evaluated by its effect on cell viability, nuclear morphology, cell cycle progression, expression of protein markers for apoptosis, and mitochondrial membrane potential (Delta psi m). These results showed that artocarpin caused a reduction of cell viability in a concentration-dependent manner and an alteration of cell and nuclear morphology. Moreover, the percentage of the sub-G1 phase formation was elevated dose-dependently. Artocarpin induced activation of caspase 8 and 10 as indicated by stronger signal intensity of cleaved-caspase 8 and weaker signal intensity of caspase 10 markers detected after artocarpin treatment. In addition, we also noticed the activation of caspase 3 by artocarpin. There were negligible changes in mitochondrial membrane potential (Delta psi m) due to artocarpin treatment. All together, these data indicated that artocarpin induced apoptosis in T47D cells possibly via an extrinsic pathway.
Arung
Enos Tangke
ET
Stem Cell and Cancer Institute, Jalan Ahmad Yani no. 2, Pulomas, Jakarta, 13210, Indonesia. tangkearung@agr.kyushu-u.ac.jp
Wicaksono
Britanto Dani
BD
Handoko
Yohana Ayupriyanti
YA
Kusuma
Irawan Wijaya
IW
Shimizu
Kuniyoshi
K
Yulia
Dina
D
Sandra
Ferry
F
D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D031622:Artocarpus / Q000633:toxicity*; D001943:Breast Neoplasms / Q000473:pathology* / Q000517:prevention & control; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D003603:Cytotoxins / Q000302:isolation & purification / Q000633:toxicity*; D006131:Growth Inhibitors / Q000633:toxicity*; D006801:Humans; D037241:Mannose-Binding Lectins / Q000302:isolation & purification / Q000633:toxicity*; D037121:Plant Lectins / Q000302:isolation & purification / Q000633:toxicity*
D003603:Cytotoxins; D006131:Growth Inhibitors; D037241:Mannose-Binding Lectins; D037121:Plant Lectins; C090683:artocarpin lectin