Induction of Apoptosis by Buckwheat Trypsin Inhibitor in Chronic Myeloid Leukemia K562 Cells

Wang, Zhuan Hua; Gao, Li; Li, Yu Ying; Zhang, Zheng; Yuan, Jing; Wang, Hong Wei; Zhang, Li; Zhu, Lihong

doi:10.1248/bpb.30.783

Cited by 20 publications

(11 citation statements)

References 18 publications

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“…A Cytochrome C Detection kit and Caspase-3, -8 and-9 Colorimetric Assay kits were obtained from BioVision (Mountain View, CA, USA). The rBTI was prepared in our laboratory by cloning, expression and one-step affinity purification as described previously (22,23). All other chemicals used were of analytical grade.…”

Section: Methodsmentioning

confidence: 99%

“…The DNA of the H22 cells treated with rBTI was extracted according to a procedure described in a previous study by our group (23). The extracted DNA was analyzed on a 1.0% agarose gel (Sigma-Aldrich) with the GeneGenius Bio Imaging system (SynGene, Frederick, MD, USA) and observed under ultraviolet light with an FV1000 fluorescent microscope (Olympus, Tokyo, Japan).…”

Section: Methodsmentioning

confidence: 99%

“…Previous studies by our group revealed that a trypsin inhibitor from buckwheat was able to markedly inhibit the proliferation of the IM-9 and K562 cell lines in vitro (22,23). In order to elucidate whether the recombinant buckwheat trypsin inhibitor (rBTI) has the same effect in vivo and which apoptotic pathway is activated following rBTI treatment, the effect of rBTI treatment on the proliferation of H22 hepatic carcinoma cells was investigated in vitro and in vivo .…”

Section: Introductionmentioning

confidence: 95%

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Anti-tumoral effects of a trypsin inhibitor derived from buckwheat in vitro and in vivo

Bai

Feng

Hao

et al. 2015

Molecular Medicine Reports

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Native buckwheat, a common component of food products and medicine, has been observed to inhibit cancer cell proliferation in vitro. The aim of the present study was to evaluate the in vitro and in vivo anti-tumoral effects of recombinant buckwheat trypsin inhibitor (rBTI) on hepatic cancer cells and the mechanism of apoptosis involved. Apoptosis in the H22 cell line induced by rBTI was identified using MTT assays, DNA electrophoresis, flow cytometry, morphological observation of the nuclei, measurement of cytochrome C and assessment of caspase activation. It was identified that rBTI decreases cell viability by inducing apoptosis, as evidenced by the formation of apoptotic bodies and DNA fragmentation. rBTI-induced apoptosis occurred in association with mitochondrial dysfunction, leading to the release of cytochrome C from the mitochondria to the cytosol, as well as the activation of caspase-3, -8 and -9. In conclusion, the results of the present study suggested that rBTI specifically inhibited the growth of the H22 hepatic carcinoma cell line in vitro and in vivo in a concentration-dependent and time-dependent manner, while there were minimal effects on the 7702 normal liver cell line. In addition, rBTI-induced apoptosis in H22 cells was, at least in part, mediated by a mitochondrial pathway via caspase-9.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 95%

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Anti-tumoral effects of a trypsin inhibitor derived from buckwheat in vitro and in vivo

Bai

Feng

Hao

et al. 2015

Molecular Medicine Reports

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“…In addition, the primary investigation indicated that recombinant buckwheat trypsin inhibitor (rBTI) could inhibit the proliferation in certain tumor cell lines, such as EC9706, Hep G2, HeLa, and other solid tumor cells. 14,15 Molecular mechanisms of tumor cell proliferation inhibited by rBTI may be involved in the disorder of mitochondrial membrane potential and mitochondrial dysfunction. Thus, in this article, we will focus on the molecular mechanisms by which cells coordinate the mitochondria and mitophagy, 16 as induced by rBTI, and also examine the relationship between autophagy and reactive oxygen species (ROS).…”

Section: ■ Introductionmentioning

confidence: 99%

Recombinant Buckwheat Trypsin Inhibitor Induces Mitophagy by Directly Targeting Mitochondria and Causes Mitochondrial Dysfunction in Hep G2 Cells

Wang

Ren

et al. 2015

J. Agric. Food Chem.

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Mitochondria are essential targets for cancer chemotherapy and other disease treatments. Recombinant buckwheat trypsin inhibitor (rBTI), a member of the potato type I proteinase inhibitor family, was derived from tartary buckwheat extracts. Our results showed that rBTI directly targeted mitochondria and induced mitochondrial fragmentation and mitophagy. This occurs through enhanced depolarization of the mitochondrial membrane potential, increasing reactive oxygen species (ROS) generation associated with the rise of the superoxide dismutase and catalase activity and glutathione peroxidase (GSH) content, and changes in the GSH/oxidized glutathione ratio. Mild and transient ROS induced by rBTI were shown to be important signaling molecules required to induce Hep G2 mitophagy to remove dysfunctional mitochondria. Furthermore, rBTI could directly induce mitochondrial fragmentation. It was also noted that rBTI highly increased colocalization of mitochondria in treated cells compared to nontreated cells. Tom 20, a subunit of the translocase of the mitochondrial outer membrane complex responsible for recognizing mitochondrial presequences, may be the direct target of rBTI.

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“…This study also showed that the trypsin inhibitory activity was responsible for the cytotoxic and pro-apoptotic functions as chemical modification of the inhibitors, by blocking its arginine residue, resulted in the loss of these activities. The cytotoxic effect was also seen in the recombinant form of BWI-1 (rBTI) on multiple myeloma IM-9 cells at 200 μg/ml [46] and myeloid leukemia K562 cells at 12.5 to 200 μg/ml [47] via induction of apoptosis. Li et al [48] demonstrated that the mechanism involved in the cytotoxic effect and proapoptotic properties of rBTI was through the action of caspases as well as the increased permeabilization of the mitochondria.…”

Section: Plant Protease Inhibitorsmentioning

confidence: 99%

The role of nutraceutical proteins and peptides in apoptosis, angiogenesis, and metastasis of cancer cells

Mejía

Dia

2010

Cancer Metastasis Rev

152

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The process of carcinogenesis is complex and not easy to eliminate. It includes the initial occurrence of genetic alterations which can lead to the inactivation of tumor-suppressor genes and further accumulation of genetic alterations during tumor progression. Looking for food and food components with biological properties, collectively called nutraceuticals, that can hinder such alterations and prevent the inactivation of tumor-suppressor genes is a very promising area for cancer prevention. Proteins and peptides are one group of nutraceuticals that show potential results in preventing the different stages of cancer including initiation, promotion, and progression. In this review, we summarized current knowledge on the use of nutraceutical proteins and peptides in cancer prevention and treatment. We focused on the role of plant protease inhibitors, lactoferrin and lactoferricin, shark cartilage, plant lectins, and lunasin in the apoptosis, angiogenesis, and metastasis of cancer cells. Also included are studies on bioavailability and clinical trials conducted on these promising proteins and peptides.

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Induction of Apoptosis by Buckwheat Trypsin Inhibitor in Chronic Myeloid Leukemia K562 Cells

Cited by 20 publications

References 18 publications

Anti-tumoral effects of a trypsin inhibitor derived from buckwheat in vitro and in vivo

Anti-tumoral effects of a trypsin inhibitor derived from buckwheat in vitro and in vivo

Recombinant Buckwheat Trypsin Inhibitor Induces Mitophagy by Directly Targeting Mitochondria and Causes Mitochondrial Dysfunction in Hep G2 Cells

The role of nutraceutical proteins and peptides in apoptosis, angiogenesis, and metastasis of cancer cells

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