Recombinant expression, different downstream processing of the disulfide-rich anti-tumor peptide Ranpirnase and its effect on the growth of human glioma cell line SHG-44

Wang, Xiaomin; Guo, Zhan‐Yun

doi:10.3892/br.2013.138

Cited by 8 publications

(7 citation statements)

References 12 publications

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“…has indicated that Onconase may inhibit cell growth in the glioma SHG-44 cell line (26). In the present study, the results demonstrated that RC-RNase exerts antitumor activity on the human glioblastoma DBTRG, GBM8901 and GBM8401 cell lines.…”

Section: A B Csupporting

confidence: 56%

“…These results suggest that a number of the GBM8401 and GBM8901 cells may be resistant to RC-RNase. However, a previous study has revealed that Onconase can induce cytotoxic effects in the human glioma SHG-44 cell line (26), and the present study demonstrated that RC-RNase can exert cytotoxic effects on the human glioblastoma DBTRG, GBM8901 and GBM8401 cell lines. Overall, these studies suggest that frog ribonucleases exert potential antitumor effects on glioblastoma cells.…”

Section: Discussionmentioning

confidence: 80%

“…In particular, Onconase has been used as an antitumor agent in clinical trials (7,19,25). Additionally, a previous study reported that Onconase exerts a cytotoxic effect on the human glioma SHG-44 cell line (26). This result indicated that frog ribonuclease may be a potential antitumor agent for the therapy of brain tumors arising from glial cells.…”

Section: Introductionmentioning

confidence: 81%

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Rana catesbeiana ribonuclease induces cell apoptosis via the caspase-9/-3 signaling pathway in human glioblastoma DBTRG, GBM8901 and GBM8401 cell lines

Chen¹,

Yiang²,

Lin³

et al. 2015

Oncology Letters

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Abstract. Human glioblastoma multiforme is one of the most aggressive malignant brain tumor types, and the mean survival time of patients with a brain tumor is <2 years when traditional therapies are administered. Thus, numerous studies have focused on the development of novel treatments for brain tumors. Frog ribonucleases, such as Onconase and Rana catesbeiana ribonuclease (RC-RNase), exert antitumor effects on various tumor cells, including cervical cancer, breast cancer, hepatoma, leukemia, pancreatic cancer and prostate cancer cells. In addition, frog Onconase has been applied as a treatment in clinical trials. However, the antitumor effects of frog ribonucleases on brain tumors are unclear. Previous studies have indicated that RC-RNase demonstrates a decreased cytotoxic effect in normal cells compared with Onconase. Therefore, the present study investigated the ability of RC-RNase to exert antitumor activities on human glioblastoma.It was found that RC-RNase inhibits the growth of the human glioblastoma DBTRG, GBM8901 and GBM8401 cells. In addition, the present study revealed that RC-RNase induces caspase-9/-3 activity and triggers the apoptotic cell death pathway in human glioblastoma cells. Notably, it was also demonstrated that RC-RNase effectively inhibits the growth of human glioblastoma tumors in a nude mouse model. Overall, the present study indicates that RC-RNase may be a potential agent for the treatment of human glioblastoma.

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Section: A B Csupporting

confidence: 56%

Section: Discussionmentioning

confidence: 80%

Section: Introductionmentioning

confidence: 81%

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Rana catesbeiana ribonuclease induces cell apoptosis via the caspase-9/-3 signaling pathway in human glioblastoma DBTRG, GBM8901 and GBM8401 cell lines

Chen¹,

Yiang²,

Lin³

et al. 2015

Oncology Letters

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“…The recombinant CTX was prepared from a GST-6′His-CTX precursor by enzymatic cleavage and in vitro refolding, according to our previously described procedure ( 34 ). The recombinant Onc was prepared through heterologous expression of an N-terminally 6xHis-tagged Onc (6xHis-Onc) precursor by enzymatic cleavage, N-terminal cyclization and in vitro refolding, according to our previously described procedure ( 35 ).…”

Section: Methodsmentioning

confidence: 99%

Chlorotoxin-conjugated onconase as a potential anti-glioma drug

Wang

Guo

2014

Oncology Letters

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Abstract. Gliomas are rarely curable malignant brain tumors arising from normal glial cells. The scorpion-derived small peptide, chlorotoxin (CTX), can selectively bind malignant gliomas. In the present study, a CTX-conjugated onconase (Onc), a small cytotoxic ribonuclease, was prepared as a potential anti-glioma drug. In this conjugate, recombinant CTX was covalently linked with recombinant Onc by reversible disulfide linkage. The chemically conjugated CTX-Onc showed much higher cytotoxicity to the cultured glioma U251 and SHG-44 cells than the physical mixture of CTX and Onc (CTX + Onc). In the nude mouse models bearing subcutaneous U251 or SHG-44 tumors, the CTX-Onc conjugate also showed improved anti-tumor effects than the CTX + Onc control. These results suggested that the reversible chemical-conjugated CTX promoted the tumor targeting of Onc, and thus the present CTX-Onc conjugate could be further developed as a potential targeted anti-glioma drug.

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“…ONC specifically evades the interaction with the cytosolic ribonuclease inhibitor (RI) owing to its particular structure which lacks the RNase A key-loop residues involved in the interaction with RI [4][5][6]. Such a capacity confers to ONC a high cytotoxic activity against several human cancer cell types, such as glioma cells [7] or lymphoma B cells [8]. Notably, ONC is currently used in Phase II and Phase IIIb clinical trials as therapy against non-small cell lung cancer and against unresectable malignant mesothelioma, respectively [9].…”

Section: Introductionmentioning

confidence: 99%

Onconase induces autophagy sensitizing pancreatic cancer cells to gemcitabine and activates Akt/mTOR pathway in a ROS-dependent manner

Fiorini

Cordani

Gotte

et al. 2015

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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Keywords: autophagy onconase pancreatic cancer reactive oxygen species (ROS) mammalian target of rapamycin (mTOR) gemcitabine Onconase® (ONC) is a member of the RNase super-family that is secreted in oocytes and early embryos of Rana pipiens. Over the last years, research interest about this small and basic frog RNase, also called ranpirnase, constantly increased because of its high cytotoxicity and anticancer properties. Onconase is currently used in clinical trials for cancer therapy; however, the precise mechanisms determining cytotoxicity in cancer cells have not yet been fully investigated. In the present manuscript, we evaluate the antitumoral property of onconase in pancreatic adenocarcinoma cells and in non-tumorigenic cells as a control. We demonstrate that ONC stimulates a strong antiproliferative and proapoptotic effect in cancer cells by reporting for the first time that ONC triggers Beclin1-mediated autophagic cancer cell death. In addition, ONC inhibits the expression of mitochondrial uncoupling protein 2 (UCP2) and of manganese-dependent superoxide dismutase (MnSOD) triggering mitochondrial superoxide ion production. ONC-induced reactive oxygen species (ROS) are responsible for Akt/ mTOR pathway stimulation determining the sensitivity of cancer cells to mTOR inhibitors and lessening autophagic stimulation. This indicates ROS/Akt/mTOR axis as a strategy adopted by cancer cells to reduce ONC-mediated cytotoxic autophagy stimulation. In addition, we demonstrate that ONC can sensitize pancreatic cancer cells to the standard chemotherapeutic agent gemcitabine allowing a reduction of drug concentration when used in combination settings, thus suggesting a lowering of chemotherapy-related side effects. Altogether, our results shed more light on the mechanisms lying at the basis of ONC antiproliferative effect in cancer cells and support its potential use to develop new anticancer strategies.

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Recombinant expression, different downstream processing of the disulfide-rich anti-tumor peptide Ranpirnase and its effect on the growth of human glioma cell line SHG-44

Cited by 8 publications

References 12 publications

Rana catesbeiana ribonuclease induces cell apoptosis via the caspase-9/-3 signaling pathway in human glioblastoma DBTRG, GBM8901 and GBM8401 cell lines

Rana catesbeiana ribonuclease induces cell apoptosis via the caspase-9/-3 signaling pathway in human glioblastoma DBTRG, GBM8901 and GBM8401 cell lines

Chlorotoxin-conjugated onconase as a potential anti-glioma drug

Onconase induces autophagy sensitizing pancreatic cancer cells to gemcitabine and activates Akt/mTOR pathway in a ROS-dependent manner

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