Ribonucleases of different origins with a wide spectrum of medicinal applications

Fang, Evandro Fei; Ng, Tzi Bun

doi:10.1016/j.bbcan.2010.09.001

Cited by 78 publications

(87 citation statements)

References 128 publications

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“…55), there are still some bottlenecks with regard to the development of protein therapeutics in humans. For example, proteins would be digested after oral intake and whether the fragments produced still remain biologically active needs investigation.…”

Section: Discussionmentioning

confidence: 99%

Momordica Charantia Lectin, a Type II Ribosome Inactivating Protein, Exhibits Antitumor Activity toward Human Nasopharyngeal Carcinoma Cells In Vitro and In Vivo

Fang

Zhang

et al. 2012

Cancer Prevention Research

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The incidence of nasopharyngeal carcinoma (NPC) remains high in endemic regions, including southern China, northern Africa, and North America. One of the promising therapeutic approaches on NPC is drug screening from natural products, such as components from traditional Chinese medicine. In this study, the antitumor activity of Momordica charantia lectin (MCL), a type II ribosome inactivating protein from bitter gourd, on NPC was investigated. MCL evinced potent cytotoxicity toward NPC CNE-1 (IC 50 ¼ 6.9) and CNE-2 (IC 50 ¼ 7.4) cells but minimally affected normal NP 69 cells. Further investigation disclosed that MCL induced apoptosis, DNA fragmentation, G 1 -phase arrest, and mitochondrial injury in both types of NPC cells. The reduction of cyclin D1 and phosphoretinoblastoma (Rb) protein expression contributed to arrest at G 1 -phase of the cell cycle. These events were associated with regulation of mitogen-activated protein kinases (MAPK; including p38 MAPK, JNK, and ERK) phosphorylation and promoted downstream nitric oxide (NO) production. Concurrent administration of the p38 MAPK inhibitor SB-203580 significantly diminished NO production and lethality of MCL toward NPC cells. Further studies revealed that MCL increased cytochrome c release into the cytosol, activated caspases-8, -9, and -3, and enhanced production of cleaved PARP, subsequently leading to DNA fragmentation and apoptosis. Finally, an intraperitoneal injection of MCL (1.0 mg/kg/d) led to an average of 45% remission of NPC xenograft tumors subcutaneously inoculated in nude mice. This is the first article that unveils the potential of a type II RIP, MCL, for prevention and therapy of NPC.

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Section: Discussionmentioning

confidence: 99%

Momordica Charantia Lectin, a Type II Ribosome Inactivating Protein, Exhibits Antitumor Activity toward Human Nasopharyngeal Carcinoma Cells In Vitro and In Vivo

Fang

Zhang

et al. 2012

Cancer Prevention Research

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“…[1][2][3][4][5] The antitumor activity was shown for BS-RNase from bovine seminal, [6][7][8][9] onconase from oocytes of Rana pipiens, [10][11][12] bovine pancreatic RNase A, 13 cSBL and jSBL RNases from Rana catesbeiana and Rana japonica, 14 microbial RNases [15][16][17] and conjugates of RNases with various molecules. [18][19][20] One of the properties that are important for potential therapeutic application of RNases is their ability to induce cancer cell death by apoptosis.…”

Section: Introductionmentioning

confidence: 99%

Ribonuclease binase inhibits primary tumor growth and metastases via apoptosis induction in tumor cells

et al. 2013

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“…However, the potencies of the antiproliferative and HIV-1 reverse transcriptase inhibitory activities are higher than those of the majority of other mushrooms reported previously. 32 RNase-controlled RNA degradation is a determining factor in the control of gene expression, maturation and turnover, which are further associated with the progression of cancers and infectious diseases. Fang and Ng 32 presented a review of the representative RNases of fungal, bacterial, plant and animal origins and outlined their potential medicinal value in the treatment of tumor and AIDS.…”

Section: Discussionmentioning

confidence: 99%

Purification and characterization of a novel RNase with antiproliferative activity from the mushroom Lactarius flavidulus

Wang

2011

J Antibiot

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A 14.6-kDa RNase, with a pH optimum of 5.5 and a temperature optimum of 70 1C, was isolated from dried fruiting bodies of the edible mushroom Lactarius flavidulus. The purification procedure involved, in succession, ion exchange chromatography on DEAE-cellulose, CM-cellulose and SP-Sepharose, and finally FPLC-gel filtration on Superdex 75. The RNase was adsorbed on all three ion exchangers. The ranking of its activity toward various polyhomoribonucleotides was poly(C) 4 poly(G) 4 poly(A) 4 poly(U). It suppressed proliferation of HepG2 cells and L1210 cells with an IC 50 of 3.19 lM and 6.52 lM, respectively. It also inhibited the activity of HIV-1 reverse transcriptase with an IC 50 of 2.55 lM. The Journal of Antibiotics (2012) 65, 67-72; doi:10.1038/ja.2011; published online 21 December 2011Keywords: antiproliferative; Lactarius flavidulus; mushroom; RNase INTRODUCTIONThe literature on Lactarius flavidulus is limited to only two reports. Peranylphenols isolated from the mushroom were designated as flavidulols A, B and C, 1-2 which displayed immunosuppressive activity on proliferation of mouse lymphocytes induced by Con A and lipopolysaccharide. 2 The literature on other Lactarius species is more abundant but work related to proteins is confined to five papers on lectins and one paper on an enzyme. Panchak and Antonyuk described the purification of a lectin from fruiting bodies of L. pergamenus 3 and L. rufus 4 and another three lectins have been purified from L. deterrimus, 5 L. lignyotus 6 and L. deliciosus. 7 RNases are found in a host of organisms. Barnase and binase are RNases purified from the bacteria Bacillus amiloliquefaciens and B. internedius, respectively. Despite similarities in structure and physicochemical and catalytic activities, the former is dependent on multifunctional Spo0A regulator controlling sporulation, biofilm formation and cannibalism, whereras binase is synthesized under phosphate starvation. Barnase and binase show some differences in practical applications. Both have been found to be useful in cancer research because of success in targeted delivery and selectivity towards tumor cells. 8 Plant RNases can be used as antiproliferative agents targeting human tumors growing in mice. 9 Onconase from the frog Rana pipiens has antitumor activity and clinical trials on patients with breast, kidney, lung and pancreatic cancers have been carried out. 10 RNases have been isolated from a lot of mushrooms including portabella mushroom, 11 Dictyophora indusiata, 12 Hypsizigus marmoreus, 13 Lyophyllum shimeiji, 14 Pleurotus djamar, 15 Pleurotus eryngii, 16 Russula delica 17 and Russulus virescens. 18 Mushrooms are abundant in bioactive proteins encompassing lectins, antifungal proteins, ribosome inactivating proteins and RNases. 16 RNases isolated from different mushroom species may have distinct N-terminal sequences, pH and temperature optima, and polyhomoribonucleotide specificities. 19 In view of this observation and the meager literature on the mushroom L. flavidulus in particular and on p...

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Ribonucleases of different origins with a wide spectrum of medicinal applications

Cited by 78 publications

References 128 publications

Momordica Charantia Lectin, a Type II Ribosome Inactivating Protein, Exhibits Antitumor Activity toward Human Nasopharyngeal Carcinoma Cells In Vitro and In Vivo

Momordica Charantia Lectin, a Type II Ribosome Inactivating Protein, Exhibits Antitumor Activity toward Human Nasopharyngeal Carcinoma Cells In Vitro and In Vivo

Ribonuclease binase inhibits primary tumor growth and metastases via apoptosis induction in tumor cells

Purification and characterization of a novel RNase with antiproliferative activity from the mushroom Lactarius flavidulus

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