Cancer-Selective Induction of Apoptosis by Leczyme

Tatsuta, Takeo; Sugawara, Shigeki; Takahashi, Kyoko; Ogawa, Yukiko; Hosono, Masahiro; Nitta, Kazuo

doi:10.3389/fonc.2014.00139

Cited by 15 publications

(12 citation statements)

References 29 publications

(38 reference statements)

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“…Cell apoptosis, proliferation and differentiation are all basic, vital functions of cells, which are closely associated; imbalances in these functions have been associated with tumor development (16,17). In general, apoptosis has a negative regulatory role in cancer cells and may inhibit tumor growth (18). Consistent with the increase in apoptosis observed in the present study, inhibition of Bcl-2 expression in NHERF1 knockdown cells was detected.…”

Section: Discussionsupporting

confidence: 80%

Targeting of NHERF1 through RNA interference inhibits the proliferation and migration of metastatic prostate cancer cells

Jiao²,

Hao

et al. 2015

Oncology Letters

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Abstract. The present study aimed to investigate the effects of Na + /H + exchanger regulatory factor 1 (NHERF1) gene knockdown, using short-hairpin RNA (shRNA), on the malignant behaviors of prostate cancer cells. A pSuper.puro NHERF1 shRNA vector was transfected into PC-3M prostate cancer cells using Lipofectamine 2000. Stable cell lines were obtained and NHERF1 knockdown was verified through western blot analysis. MTT assays were then used to measure PC-3M cell proliferation; in addition, cell migration was assessed using a wound healing assay. Flow cytometry was employed in order to determine the effects of NHERF1 knockdown on apoptosis. Expression levels of apoptotic pathway proteins B cell lymphoma-2 (Bcl-2) and Bcl-2-associated X protein were then determined by western blot analysis. The results demonstrated that shRNA knockdown of NHERF1 significantly suppressed the proliferation of PC-3M cells by >50%. In addition, knockdown of NHERF1 significantly inhibited the migration of PC-3M cells. PC-3M cells harboring NHERF1 shRNA exhibited significantly increased apoptosis, with an ~4-fold increase compared with that of the parental PC-3M cells and cells transfected with an empty vector. Furthermore, the results revealed that knockdown of NHERF1 reduced the protein expression of Bcl-2, although the expression of Bax was unaltered. In conclusion, NHERF1 knockdown using shRNA inhibited the proliferation and migration of PC-3M cells and promoted apoptosis, highlighting the role of NHERF1 in prostate cancer progression.

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Section: Discussionsupporting

confidence: 80%

Targeting of NHERF1 through RNA interference inhibits the proliferation and migration of metastatic prostate cancer cells

Jiao²,

Hao

et al. 2015

Oncology Letters

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“…SBL induces cell death in various types of human cancer cells ( 7 ). To examine the antitumor effect of SBL on breast cancer cells, we used one estrogen-positive cell line (MCF-7) and two estrogen-negative cell lines (SK-BR-3 and MDA-MB231) for a cell viability assay.…”

Section: Resultsmentioning

confidence: 99%

“…SBL also exhibits a prominent antitumor effect on many types of cancer and tumor cells, such as breast, cervical, oral cancer, glioblastoma, and T-cell leukemia, but not normal cells, such as keratinocytes, fibroblasts, and lymphocytes ( 3 – 6 ). Moreover, the treatment of cancer cells with SBL ultimately leads to cell death ( 7 ). In mice with ascites tumor cells, the injection of SBL inhibits tumor growth and prolongs the life span, and sialidase protects cancer cells from SBL toxicity ( 8 ).…”

Section: Introductionmentioning

confidence: 99%

RNase activity of sialic acid-binding lectin from bullfrog eggs drives antitumor effect via the activation of p38 MAPK to caspase-3/7 signaling pathway in human breast cancer cells

Kariya

Tatsuta

Sugawara

et al. 2016

International Journal of Oncology

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Sialic acid-binding lectin obtained from bullfrog eggs (SBL) induces cell death in cancer cells but not in normal cells. This antitumor effect is mediated through its ribo-nuclease (RNase) activity. However, the underlying molecular mechanisms remain unclear. We found that the p38 mitogen-activated protein kinase (MAPK) signaling pathway was activated when SBL induced cell death in three human breast cancer cell lines: SK-BR-3, MCF-7, and MDA-MB231. The suppression of p38 MAPK phosphorylation by a p38 MAPK inhibitor as well as short interference RNA knockdown of p38 MAPK expression significantly decreased cell death and increased the cell viability of SBL-treated MDA-MB231 cells. H103A, an SBL mutant lacking in RNase activity, showed decreased SBL-induced cell death compared with native SBL. However, the loss of RNase activity of SBL had no effect on its internalization into cells. The H103A mutant also displayed decreased phosphorylation of p38 MAPK. Moreover, SBL promoted caspase-3/7 activation followed by a cleavage of poly (ADP-ribose)-polymerase, whereas the SBL mutant, H103A, lost this ability. The SBL-induced caspase-3/7 activation was suppressed by the p38 MAPK inhibitor, SB203580, as well as pan-caspase inhibitor, zVAD-fmk. In the presence of zVAD-fmk, the SBL-induced cell death was decreased. In addition, the cell viability of SBL-treated MDA-MB231 cells recovered by zVAD-fmk treatment. Taken together, our results suggest that the RNase activity of SBL leads to breast cancer cell death through the activation of p38 MAPK followed by the activation of caspase-3/7.

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“…79 Sialic acid-binding lectin (SBL) is a multi-functional protein that is isolated from oocytes of Rana catesbeiana which displays caspase 3 dependent killing of cancer cells. 80 Selective treatment of cell lines with SBL revealed that SBL induces cell death on estrogen receptor (ER)-positive breast tumors but not on ER-negative breast tumors. 81 The anti-tumor effect of SBLtreated ER-positive breast tumors is accompanied by the downregulation of ER and Bcl-2.…”

Section: Antibodies As Mimics Of Lectinsmentioning

confidence: 99%

Harnessing benefit from targeting tumor associated carbohydrate antigens

Kieber‐Emmons¹

2017

Eur J Exp Bio

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Integrating additive or synergistic antitumor effects that focus on distinct elements of tumor biology are the most rational strategies for cancer treatment. Treatments for breast cancer have increased overall survival, but remain limited by lack of efficacy in a subset of breast cancer patients. The real challenge is to define what elements of tumor biology make the most sense to be integrated. An emerging strategy is to consider a systems biology approach to impact multiple interactions in networks as compare with hitting a specific protein-protein interaction target. In this review, we consider how targeting tumor associated carbohydrate antigens (TACA) that are fundamental to signal pathways might be tailored to harness benefit from combination therapy of sustained immunity with chemotherapy. An approach we are developing makes use of a carbohydrate mimetic peptide (CMP) to induce polyspecific antibodies, which by their nature have numerous on and off target effects. Linking multi-target TACA recognition with mechanisms affecting tumor growth in the context of network heterogeneity and concepts of immune surveillance to tumor cells and the type of breast cancer patients that would benefit from such an approach provides a novel integrative treatment.

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Cancer-Selective Induction of Apoptosis by Leczyme

Cited by 15 publications

References 29 publications

Targeting of NHERF1 through RNA interference inhibits the proliferation and migration of metastatic prostate cancer cells

Targeting of NHERF1 through RNA interference inhibits the proliferation and migration of metastatic prostate cancer cells

RNase activity of sialic acid-binding lectin from bullfrog eggs drives antitumor effect via the activation of p38 MAPK to caspase-3/7 signaling pathway in human breast cancer cells

Harnessing benefit from targeting tumor associated carbohydrate antigens

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