Thesis (M.Sc. in Pharm)--Chulalongkorn University, 2012

Anoikisis apoptosis that is induced by loss of adhesion. Anoikisis recognized as a key inhibitory process of cancer metastasis. Because lung cancer cells possess an ability to resist anoikisresulting in a high rate of metastasis and death, the present study aimed to investigate a possible anoikis-sensitizing effect of artonin E (AE). AE was extracted from bark of Artocarpusgomezianus. Anoikis sensitization of AE was investigated in H460 human lung cancer cells. The viable cells were measured by 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) and level of anoikis-related proteins was determined by western blot analysis. AE was shown to enhance H460 cell anoikisin a concentration-dependent manner. We investigated the underlying mechanism of AE and found that AE sensitized the cells by down-regulating antiapoptotic myeloid leukemia cell sequence 1 (Mcl-1) protein but had no significant effect on other proteins including Bcl-2, Bcl-2-associated X protein (Bax), cav-1 and p53. Furthermore, anoikis sensitization of AE was consistently observed in A549 and H292 lung cancer cells. The present study demonstrates a novel activity of AE on lung cancer cell anoikis for the first time which might lead to the development of a new strategy for lung cancer therapy.