earticle

영어

In this study, we aimed to examine the cellular and molecular mechanisms of KTH-13 (4-isopropyl-2,6-bis(1-phenylethyl)phenol) which is derived from Cordyceps staphylindaecola in the cancer cells survival. The apoptotic effect of KTH-13 on various cancer cells, such as C6 glioma, MDA-MB-231 breast cancer, and A549 cells, was determined by MTT assay, and result showed that KTH-13 (0-100mM) dramatically inhibited the cancer cell survival. IC50 of KTH13 were 60.549, 53.512, >100, in C6, MDA-MB-231, and A549, respectively. DNA fragmentation result revealed that MDA-MB-231 cells treated with KTH-13 100mM undergoes apoptosis. To understand the action mechanism of KTH-13, the effect of KTH-13 on caspase which is key regulator of apoptosis was verified. The amount of cleaved capspase-3 and 7, executioner caspases, was increased by KTH-13 treatment, at time dependent (capspase-3 case) and dose dependent manner (caspase-7 case). And the cleavage of caspase-9 which is initiator caspase was also elevated in KTH-13 treated MDA-MB-231 cells showing time dependent manner. However, caspase-8 was not regulated by KTH-13, indicating KTH-13 specifically targets caspase-9 signal. As caspase-9 is closely associated with intrinsic pathway, the involvement of bcl-2 family was identified. Bax, pro-apoptotic molecule, was up-regulated whereas Bcl-2, anti-apoptotic protein, was down-regulated. And the Bax/Bcl-2 ratio was increased about 10 times. Then, the survival signal was also observed. The phosphorylation of Akt and p85 was diminished by KTH-13 treatment at 2,4,6 and 8 hour. Collectively, results suggest that KTH-13 induces cancer cells apoptosis via caspase3, 7, 8 and Bcl-2 family signaling pathway. And the Akt and p85 is also involved in KTH-13 action mechanism.