Leczyme: A New Candidate Drug for Cancer Therapy

Abstract

Sialic acid-binding lectin (SBL), isolated from oocytes of Rana catesbeiana, is leczyme and has both lectin and ribonuclease (RNase) activities. A remarkable antitumor effect of SBL has also been reported. SBL agglutinates various kinds of tumor cells but not normal cells. SBL agglutination activity is not affected by mono- or oligosaccharides. However, SBL-induced agglutination and antitumor effects are inhibited by sialomucin but not asialomucin. In addition, SBL has very little effect on sialidase-treated cells. SBL causes cancer-selective induction of apoptosis by multiple signaling pathways, which target RNA. Synergistic antitumor effects with other molecules, such as tumor necrosis factor-related apoptosis ligand (TRAIL) and interferon-γ (IFN-γ), have been reported. Thus, SBL may be a novel candidate molecule for anticancer drug development. Sialoglycoconjugates on the tumor cell surface may be associated with lectin activity and antitumor effects of SBL. We review the properties of SBL, particularly its lectin, RNase, and antitumor activities, and comprehensively examine the potential application of SBL for clinical purposes.

Ribonucleases. Possible New Approach in Cancer Therapy

“…The recently discovered double-stranded RNase activity of ranpirnase suggests another mechanism for inducing cell death/apoptosis in malignant phenotypes via the RNA interference mechanism involving siRNA and miRNA [27]. Another enzyme sialic acid-binding lectin (SBL), isolated from oocytes of Rana catesbeiana, is leczyme and has both lectin and RNase activities [8]. SBL agglutinates various kinds of tumor cells but not normal cells.…”

“…However, SBL-induced agglutination and antitumor effects are inhibited by sialomucin but not asialomucin. SBL causes cancerselective induction of apoptosis by multiple signaling pathways, which target RNA [8].…”

“…Today, several RNases allocated as possible candidates for anticancer agents [5][6][7][8][9]. The interferon (IFN) antiviral investigations and prostate cancer genetics have merged on a single-strand specific, regulated endoribonuclease.…”

Approaches to Endow Ribonucleases with Antitumor Activity: Lessons Learned from the Native Cytotoxic Ribonucleases

“…Unlike ONC and Amph, these latter ones agglutinate cancer cells [47][48][49] binding to cell membrane glycoproteins with a high content of sialic acids [47,49]. It is also proposed, like for ONC and Amph, that these leczymes require an internalization process to trigger apoptosis [50]; however compared to them, clinical trials and studies on animal models are needed to unveil their mechanism of antitumor activity and clinical potential.…”

Ribonucleases with Antiproliferative Properties: Molecular Biological and Biochemical Characteristics

“…В одной из обзорных работ T. Tatsuta и соавт. [57] при-ведены сведения о лектине из ооцитов R. catesbeiana, связывающем сиаловую кислоту (SBL, sialic acid-binding lectin). Подробно описаны РНКазная активность SBL и антипролиферативный эффект in vivo и in vitro на моделях мышиных лимфолейкозов Р388, L1210 и на широкой панели лейкозов человека [58,59].…”