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Mar. Drugs 2017, 15(7), 221; doi:10.3390/md15070221

Mertensene, a Halogenated Monoterpene, Induces G2/M Cell Cycle Arrest and Caspase Dependent Apoptosis of Human Colon Adenocarcinoma HT29 Cell Line through the Modulation of ERK-1/-2, AKT and NF-κB Signaling

1
Institut Pasteur de Tunis, Laboratoire de Toxines Alimentaires, LR11IPT08 Laboratoire des Venins et Molécules Thérapeutiques, 1002 Tunis, Tunisia
2
Faculté des Sciences de Bizerte, Université de Carthage, 1002 Tunis, Tunisia
3
Institut Pasteur de Tunis, LR11IPT04 Laboratoire d’Epidémiologie Moléculaire et de Pathologie Expérimentale Appliquée Aux Maladies Infectieuses, 1002 Tunis, Tunisia
4
Université de Tunis El Manar, 1068 Tunis, Tunisia
5
Department of Pharmacognosy and Chemistry of Natural Products, Faculty of Pharmacy, National and Kapodistrian University of Athens, Panepistimiopolis Zografou, Athens 15771, Greece
6
Institut Pasteur de Tunis, LR11IPT02 Laboratoire de Recherche sur la Transmission, le Contrôle et l’Immunobiologie des Infections, 1002 Tunis, Tunisia
*
Authors to whom correspondence should be addressed.
Received: 17 May 2017 / Revised: 29 June 2017 / Accepted: 7 July 2017 / Published: 20 July 2017
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Abstract

Conventional treatment of advanced colorectal cancer is associated with tumor resistance and toxicity towards normal tissues. Therefore, development of effective anticancer therapeutic alternatives is still urgently required. Nowadays, marine secondary metabolites have been extensively investigated due to the fact that they frequently exhibit anti-tumor properties. However, little attention has been given to terpenoids isolated from seaweeds. In this study, we isolated the halogenated monoterpene mertensene from the red alga Pterocladiella capillacea (S.G. Gmelin) Santelices and Hommersand and we highlight its inhibitory effect on the viability of two human colorectal adenocarcinoma cell lines HT29 and LS174. Interestingly, exposure of HT29 cells to different concentrations of mertensene correlated with the activation of MAPK ERK-1/-2, Akt and NF-κB pathways. Moreover, mertensene-induced G2/M cell cycle arrest was associated with a decrease in the phosphorylated forms of the anti-tumor transcription factor p53, retinoblastoma protein (Rb), cdc2 and chkp2. Indeed, a reduction of the cellular level of cyclin-dependent kinases CDK2 and CDK4 was observed in mertensene-treated cells. We also demonstrated that mertensene triggers a caspase-dependent apoptosis in HT29 cancer cells characterized by the activation of caspase-3 and the cleavage of poly (ADP-ribose) polymerase (PARP). Besides, the level of death receptor-associated protein TRADD increased significantly in a concentration-dependent manner. Taken together, these results demonstrate the potential of mertensene as a drug candidate for the treatment of colon cancer. View Full-Text
Keywords: Pterocladiella capillacea; mertensene; colon cancer; cell cycle arrest; apoptosis; cellular effectors Pterocladiella capillacea; mertensene; colon cancer; cell cycle arrest; apoptosis; cellular effectors
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Tarhouni-Jabberi, S.; Zakraoui, O.; Ioannou, E.; Riahi-Chebbi, I.; Haoues, M.; Roussis, V.; Kharrat, R.; Essafi-Benkhadir, K. Mertensene, a Halogenated Monoterpene, Induces G2/M Cell Cycle Arrest and Caspase Dependent Apoptosis of Human Colon Adenocarcinoma HT29 Cell Line through the Modulation of ERK-1/-2, AKT and NF-κB Signaling. Mar. Drugs 2017, 15, 221.

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