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Pectenotoxin-2 from Marine Sponges: A Potential Anti-Cancer Agent—A Review
Laboratory of Immunobiology, Department of Marine Life Sciences, Jeju National University, Jeju 690-756, Korea
Department of Urology, Chungbuk National University College of Medicine, Cheongju 361-763, Korea
Department of Biochemistry, College of Oriental Medicine, Dongeui University, Busan 614-052, Korea
Department of Biomaterial Control (BK21 program), Graduate School, and Blue-Bio Industry RIC, Dongeui University, Busan 614-052, Korea
* Author to whom correspondence should be addressed.
Received: 2 September 2011; in revised form: 9 October 2011 / Accepted: 19 October 2011 / Published: 2 November 2011
Abstract: Pectenotoxin-2 (PTX-2), which was first identified as a cytotoxic entity in marine sponges, has been reported to display significant cytotoxicity to human cancer cells where it inhibits mitotic separation and cytokinesis through the depolymerization of actin filaments. In the late stage of endoreduplication, the effects of PTX-2 on different cancer cells involves: (i) down-regulation of anti-apoptotic Bcl-2 members and IAP family proteins; (ii) up-regulation of pro-apoptotic Bax protein and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-receptor 1/receptor 2 (DR4/DR5); and (iii) mitochondrial dysfunction. In addition, PTX-2 induces apoptotic effects through suppression of the nuclear factor κB (NF-κB) signaling pathway in several cancer cells. Analysis of cell cycle regulatory proteins showed that PTX-2 increases phosphorylation of Cdc25c and decreases protein levels of Cdc2 and cyclin B1. Cyclin-dependent kinase (Cdk) inhibitor p21 and Cdk2, which are associated with the induction of endoreduplication, were upregulated. Furthermore, it was found that PTX-2 suppressed telomerase activity through the transcriptional and post-translational suppression of hTERT. The purpose of this review was to provide an update regarding the anti-cancer mechanism of PTX-2, with a special focus on its effects on different cellular signaling cascades.
Keywords: pectenotoxin-2; cancer; cell cycle; apoptosis
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Kim, G.-Y.; Kim, W.-J.; Choi, Y.H. Pectenotoxin-2 from Marine Sponges: A Potential Anti-Cancer Agent—A Review. Mar. Drugs 2011, 9, 2176-2187.
Kim G-Y, Kim W-J, Choi YH. Pectenotoxin-2 from Marine Sponges: A Potential Anti-Cancer Agent—A Review. Marine Drugs. 2011; 9(11):2176-2187.
Kim, Gi-Young; Kim, Wun-Jae; Choi, Yung Hyun. 2011. "Pectenotoxin-2 from Marine Sponges: A Potential Anti-Cancer Agent—A Review." Mar. Drugs 9, no. 11: 2176-2187.