Cell apoptosis induced by delta-elemene in colorectal adenocarcinoma cells via a mitochondrial-mediated pathway.
The chemical compound delta-elemene, isolated from the Chinese herbal medicine plant Curcuma Wenyujin, has been known to exert antitumor activity. In this study we demonstrated that apoptotic cell death induced by delta-elemene in DLD-1 cells was concentration-and time-dependent, and had little inhibition of the normal human liver cell line WRL-68. Apoptosis was further confirmed and quantified by DNA fragmentation ELISA, Annexin V (AnV) binding of externalized phosphatidylserine and the mitochondrial probe JC-1 using flow cytometry. The rapid increase in intracellular reactive oxygen species (ROS) levels was involved in the mechanism of cell death. Western blot analysis demonstrated that delta-elemene activated the caspase-signaling pathway, leading to the proteolysis conversion of pro-caspase-3 to activate caspase-3, and the subsequent cleavage of the caspase substrate PARP. In the process of the induction of apoptotic cell death, Bax translocated into mitochondria, a reduction in Deltapsim was observed and a release of cytochrome c and apoptosis inducing factor (AIF) from mitochondria into the cytosol occurred, indicating that cell death induced by delta-elemene was through a mitochondrial-mediated pathway.
Xie
Chun-Ying
CY
The Sixth Affiliated Hospital, SUN YAT-SEN University, Guangdong, China.
Yang
Wei
W
Li
Ming
M
Ying
Jun
J
Tao
Shu-Juan
SJ
Li
Karen
K
Dong
Jin-Hua
JH
Wang
Xi-Sha
XS
D000230:Adenocarcinoma / Q000473:pathology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000473:pathology*; D030024:Curcuma; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008928:Mitochondria / Q000502:physiology*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012717:Sesquiterpenes / Q000494:pharmacology*; D013997:Time Factors
D000972:Antineoplastic Agents, Phytogenic; D017382:Reactive Oxygen Species; D012717:Sesquiterpenes; C038905:elemene; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3