(1S,2S,3E,7E,11E)-3,7,11,15-Cembratetraen-17,2-olide, a cembrenolide diterpene from soft coral Lobophytum sp., inhibits growth and induces apoptosis in human colon cancer cells through reactive oxygen species generation.
We observed that (1S,2S,3E,7E,11E)-3,7,11,15-Cembratetraen-17,2-olide (LS-1), marine cembrenolide diterpene, inhibited growth and induced apoptosis in colon cancer cells via a reactive oxygen species (ROS) dependent mechanism. Treatment of HT-29 cells with LS-1 resulted in ROS generation, which was accompanied by disruption of mitochondrial membrane potential, cytosolic release of cytochrome c, sub-G1 peak accumulation, activation of Bid, caspase-3, -8, and -9, and cleavage of poly(ADP-ribose) polymerase (PARP) along with the suppressive expression of B cell lymphoma-2 (Bcl-2). All these effects were significantly blocked on pretreatment with the ROS inhibitor N-acetylcysteine (NAC), indicating the involvement of increased ROS in the proapoptotic activity of LS-1. Moreover, we showed that LS-1 induced the phosphorylation of c-Jun N-terminal kinase (JNK) and dephosphorylation of p38, extracellular signal-regulated kinase (ERK), Akt, Src and signal transducer and activator of transcription (STAT)3, which were effectively attenuated by NAC. In addition, the expressions of antioxidant catalase and glutathione peroxidase were abrogated by treatment using LS-1 with or without NAC. These findings reveal the novel anticancer efficacy of LS-1 mediated by the induction of apoptosis via ROS generation in human colon cancer cells.
Institute of Medical Sciences, School of Medicine, Jeju National University, Jeju 690-756, Republic of Korea.
Ji-Young
JY
Hong
Hye-Jin
HJ
Boo
Jung-Il
JI
Kang
Min-Kyoung
MK
Kim
Eun-Sook
ES
Yoo
Jin-Won
JW
Hyun
Young-Sang
YS
Koh
Gi Young
GY
Kim
Young Hee
YH
Maeng
Chang Lim
CL
Hyun
Weon Young
WY
Chang
Young Ho
YH
Kim
Young Ree
YR
Kim
Hee-Kyoung
HK
Kang
D000818:Animals; D037421:Anthozoa; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051023:BH3 Interacting Domain Death Agonist Protein / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms; D004224:Diterpenes / Q000494:pharmacology*; D005979:Glutathione Peroxidase / Q000378:metabolism; D019073:HT29 Cells; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006801:Humans; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D000094765:Glutathione Peroxidase GPX1
C576714:(1S,2S,3E,7E,11E)-3,7,11,15-cembratetraen-17,2-olide; D000970:Antineoplastic Agents; D051023:BH3 Interacting Domain Death Agonist Protein; C494814:BID protein, human; D004224:Diterpenes; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D002374:Catalase; D005979:Glutathione Peroxidase; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1; D013482:Superoxide Dismutase; D011065:Poly(ADP-ribose) Polymerases; D011494:Protein Kinases; D020169:Caspases; D000094765:Glutathione Peroxidase GPX1