- Oral presentation
- Open Access
67-kDa laminin receptor and cGMP induced cancer-selective apoptosis
© Kumazoe and Tachibana; licensee BioMed Central Ltd. 2013
- Published: 29 August 2013
- Nitric Oxide
- Multiple Myeloma
- Erectile Dysfunction
In this study, we demonstrate 67LR activated the peculiar apoptotic signalling eNOS/NO/ cGMP/protein kinase Cδ (PKCδ) pathway. Furthermore, we show the upregulation of cGMP is rate-determining process of this cell death pathway. We demonstrate cancer overexpressed negative regulator of cGMP, PDE5 attenuates the cGMP-dependent cell death induced by EGCG. Vardenafil, one of the PDE5 selective inhibitors used for treating erectile dysfunction potentiates anti-cancer effect of EGCG. These results demonstrate that cGMP elevation caused by targeting the overexpressed 67LR and PDE5 in cancer cells may be a useful approach for cancer-specific chemotherapy.
- Shanafelt TD, Call TG, Zent CS, Leis LF, Plant BL, Bowen DA, Roos M, Laumann K, Ghosh AK, Lesnick C, Lee MJ, Yang CS, Jelinek DF, Erlichman C, Kay NE: Phase 2 trial of daily, oral Polyphenon E in patients with asymptomatic, Rai stage 0 to II chronic lymphocytic leukemia. Cancer. 2013, 119: 363-370. 10.1002/cncr.27719.PubMed CentralView ArticlePubMedGoogle Scholar
- Bettuzzi S, Brausi M, Rizzi F, Castagnetti G, Peracchia G, Corti A: Chemo- prevention of human prostate cancer by oral administrationof green tea catechins in volunteers with high-grade prostate intraepithelial neoplasia: a preliminary report from a one-year Proof-of-Principle study. Cancer Res. 2006, 66: 1234-1244. 10.1158/0008-5472.CAN-05-1145.View ArticlePubMedGoogle Scholar
- Tachibana H, Koga K, Fujimura Y, Yamada K: A receptor for green tea polyphenol EGCG. Nat Struct Mol Biol. 2004, 11: 380-381. 10.1038/nsmb743.View ArticlePubMedGoogle Scholar
- Shammas MA, Neri P, Koley H, Batchu PB, Bertheau RC, Munshi V, Prabhala R, Fulciniti M, Tai Y, Steven P, Treon SP, Goyal RK, Anderson CK, Munshi NC: Specific killing of multiple myeloma cells by (-)-epigallocatechin-3-gallate extracted from green tea: biologic activity and therapeutic implications. Blood. 2006, 108: 2804-2810. 10.1182/blood-2006-05-022814.PubMed CentralView ArticlePubMedGoogle Scholar
- Tsukamoto S, Hirotsu K, Kumazoe M, Goto Y, Sugihara K, Suda T, Tsurudome Y, Suzuki T, Yamashita S, Kim Y, Huang Y, Yamada K, Tachibana H: Green tea polyphenol EGCG induces lipid-raft clustering and apoptotic cell death by activating protein kinase Cdelta and acid sphingomyelinase through a 67 kDa laminin receptor in multiple myeloma cells. Biochem J. 2012, 443: 525-534. 10.1042/BJ20111837.View ArticlePubMedGoogle Scholar
- Kumazoe M, Sugihara K, Tsukamoto S, Huang Y, Tsurudome Y, Suzuki T, Suemasu Y, Ueda N, Yamashita S, Kim Y, Yamada K, Tachibana H: 67-kDa laminin receptor increases cGMP to induce cancer-selective apoptosis. J Clin Invest. 2013, 123: 787-799.PubMed CentralPubMedGoogle Scholar
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