Targeted suppression of μ-calpain and caspase 9 expression and its effect on caspase 3 and caspase 7 in satellite cells of Korean Hanwoo cattle

TheCordycepsspecies have been widely used for treating various cancer diseases. Although the Cordyceps species have been widely known as an alternative anticancer remedy, which compounds are responsible for their anticancer activity is not fully understood. In this study, therefore, we examined the anticancer activity of 5 isolated compounds derived from the butanol fraction (Cb-BF) ofCordyceps bassiana. For this purpose, several cancer cell lines such as C6 glioma, MDA-MB-231, and A549 cells were employed and details of anticancer mechanism were further investigated. Of 5 compounds isolated by activity-guided fractionation from BF of Cb-EE, KTH-13, and 4-isopropyl-2,6-bis(1-phenylethyl)phenol, Cb-BF was found to be the most potent antiproliferative inhibitor of C6 glioma and MDA-MB-231 cell growth. KTH-13 treatment increased DNA laddering, upregulated the level of Annexin V positive cells, and altered morphological changes of C6 glioma and MDA-MB-231 cells. In addition, KTH-13 increased the levels of caspase 3, caspase 7, and caspase 9 cleaved forms as well as the protein level of Bax but not Bcl-2. It was also found that the phosphorylation of AKT and p85/PI3K was also clearly reduced by KTH-13 exposure. Therefore, our results suggest KTH-13 can act as a potent antiproliferative and apoptosis-inducing component fromCordyceps bassiana, contributing to the anticancer activity of this mushroom.

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Immunoreactivity to caspase-3, caspase-7, caspase-8, and caspase-9 forms is frequently lost in human prostate tumors

Human Pathology ◽

10.1016/j.humpath.2011.04.024 ◽

2012 ◽

Vol 43 (2) ◽

pp. 229-237 ◽

Cited By ~ 15

Author(s):

Gonzalo Rodríguez-Berriguete ◽

Laura Galvis ◽

Benito Fraile ◽

Fermín R de Bethencourt ◽

Pilar Martínez-Onsurbe ◽

...

Keyword(s):

Caspase 3 ◽

Human Prostate ◽

Caspase 8 ◽

Caspase 9 ◽

Prostate Tumors ◽

Caspase 7

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Caspase-9, caspase-3 and caspase-7 have distinct roles during intrinsic apoptosis

BMC Cell Biology ◽

10.1186/1471-2121-14-32 ◽

2013 ◽

Vol 14 (1) ◽

pp. 32 ◽

Cited By ~ 339

Author(s):

Matthew Brentnall ◽

Luis Rodriguez-Menocal ◽

Rebeka De Guevara ◽

Enrique Cepero ◽

Lawrence H Boise

Keyword(s):

Caspase 3 ◽

Intrinsic Apoptosis ◽

Caspase 9 ◽

Caspase 7

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Indole-3-Carbinol Induces Apoptosis in Human Osteosarcoma MG-63 and U2OS Cells

BioMed Research International ◽

10.1155/2018/7970618 ◽

2018 ◽

Vol 2018 ◽

pp. 1-13 ◽

Cited By ~ 2

Author(s):

Chang Min Lee ◽

Jongsung Lee ◽

Myeong Jin Nam ◽

See-Hyoung Park

Keyword(s):

Cell Sorting ◽

Caspase 3 ◽

Terminal Deoxynucleotidyl Transferase ◽

Dependent Manner ◽

Facs Analysis ◽

Caspase 9 ◽

Human Osteosarcoma ◽

Caspase 7 ◽

U2os Cells ◽

Induced Apoptosis

This study was focused on investigating the anticancer potential of indole-3-carbinol (I3C) against osteosarcoma MG-63 and U2OS cells. A wound healing assay indicated that IC3 inhibited migration of MG-63 and U2OS cells. MTT, WST-1, and colony formation assays revealed that treatment of MG-63 and U2OS cells with I3C decreased cell viability. Fluorescence-activated cell sorting (FACS) analysis showed that I3C induced apoptosis in a dose- and time-dependent manner in MG-63 and U2OS cells. Moreover, via terminal deoxynucleotidyl transferase- (TdT-) mediated dUTP-biotin nick-end labeling (TUNEL) assay, we detected that I3C induced DNA fragmentation. Western blotting demonstrated that activated forms of caspase-3, caspase-7, and caspase-9, as well as poly (ADP-ribose) polymerase (PARP) were increased in MG-63 and U2OS cells, following treatment with I3C. Furthermore, protein expression levels of FOXO3, Bax, and Bim extra-large form were increased while those of Akt, JNK, p38, phosphorylated ERK, and Bcl-xL were decreased by I3C treatment in MG-63 and U2OS cells. Thus, the study indicates that I3C may induce apoptosis in human osteosarcoma MG-63 and U2OS cells via the activation of apoptotic signaling pathways by FOXO3.

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The expression of caspase-3, caspase-7, caspase-9 and cytokeratin AE1/AE3 in goats with enzootic nasal adenocarcinoma: an immunohistochemical study

Veterinární Medicína ◽

10.17221/6981-vetmed ◽

2013 ◽

Vol 58 (No. 8) ◽

pp. 417-421 ◽

Cited By ~ 2

Author(s):

A. Aydogan ◽

M. Haligur ◽

O. Ozmen

Keyword(s):

Caspase 3 ◽

Immunohistochemical Study ◽

Histopathological Examination ◽

Tumour Cells ◽

Nasal Discharge ◽

Immunoperoxidase Technique ◽

Caspase 9 ◽

Caspase 7 ◽

Nasal Adenocarcinoma ◽

Avidin Biotin Complex

The aim of this study was to examine the expression of caspase-3, caspase-7, caspase-9 and cytokeratin AE-1/AE-3 using the avidin-biotin complex (ABC) immunoperoxidase technique in 20 goats with enzootic nasal adenocarcinoma (ENA). Clinically, dyspnoea and nasal discharge were observed in all cases. Macroscopically, polypoid and sessile masses were seen in the ethmoidal area. At the histopathological examination, tubular, papillary and mixed patterns of ENA were diagnosed. Immunohistochemically, strong positive reactions were generally seen for caspase-3, while strong to moderate and slight reactions were observed for caspase-7 and caspase-9 in the cytoplasm of the tumour cells. Positive reactions for cytokeratin AE-1/AE-3 were only seen in epithelial cells. In addition, the causative agent of ENA, retrovirus, was detected immunohistochemically in tumour cells.  

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Caspase 3 attenuates XIAP (X-linked inhibitor of apoptosis protein)–mediated inhibition of caspase 9

Biochemical Journal ◽

10.1042/bj20070288 ◽

2007 ◽

Vol 405 (1) ◽

pp. 11-19 ◽

Cited By ~ 66

Author(s):

Jean-Bernard Denault ◽

Brendan P. Eckelman ◽

Hwain Shin ◽

Cristina Pop ◽

Guy S. Salvesen

Keyword(s):

Caspase 3 ◽

Alternative Mechanism ◽

Caspase 9 ◽

Inhibitory Interaction ◽

Iap Antagonist ◽

Apoptosis Protein ◽

Caspase 7 ◽

Amplification Process ◽

Amplification Loop ◽

Executioner Caspases

During apoptosis, the initiator caspase 9 is activated at the apoptosome after which it activates the executioner caspases 3 and 7 by proteolysis. During this process, caspase 9 is cleaved by caspase 3 at Asp330, and it is often inferred that this proteolytic event represents a feedback amplification loop to accelerate apoptosis. However, there is substantial evidence that proteolysis per se does not activate caspase 9, so an alternative mechanism for amplification must be considered. Cleavage at Asp330 removes a short peptide motif that allows caspase 9 to interact with IAPs (inhibitors of apoptotic proteases), and this event may control the amplification process. We show that, under physiologically relevant conditions, caspase 3, but not caspase 7, can cleave caspase 9, and this does not result in the activation of caspase 9. An IAP antagonist disrupts the inhibitory interaction between XIAP (X-linked IAP) and caspase 9, thereby enhancing activity. We demonstrate that the N-terminal peptide of caspase 9 exposed upon cleavage at Asp330 cannot bind XIAP, whereas the peptide generated by autolytic cleavage of caspase 9 at Asp315 binds XIAP with substantial affinity. Consistent with this, we found that XIAP antagonists were only capable of promoting the activity of caspase 9 when it was cleaved at Asp315, suggesting that only this form is regulated by XIAP. Our results demonstrate that cleavage by caspase 3 does not activate caspase 9, but enhances apoptosis by alleviating XIAP inhibition of the apical caspase.

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Treatment with Melittin Induces Apoptosis and Autophagy of Fibroblast-like Synoviocytes in Patients with Rheumatoid Arthritis

Current Pharmaceutical Biotechnology ◽

10.2174/1389201021666191210110826 ◽

2020 ◽

Vol 21 (8) ◽

pp. 734-740 ◽

Cited By ~ 1

Author(s):

Shou-di He ◽

Ning Tan ◽

Chen-xia Sun ◽

Kang-han Liao ◽

Hui-jun Zhu ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Caspase 3 ◽

Joint Destruction ◽

Joint Disease ◽

Enzyme Linked Immunosorbent Assay ◽

Caspase 9 ◽

Inflammatory Processes ◽

Related Proteins ◽

Local Stimulation ◽

Fibroblast Like Synoviocytes

Background: Melittin, the major medicinal component of honeybee venom, exerts antiinflammatory, analgesic, and anti-arthritic effects in patients with Rheumatoid Arthritis (RA). RA is an inflammatory autoimmune joint disease that leads to irreversible joint destruction and functional loss. Fibroblast-Like Synoviocytes (FLS) are dominant, special mesenchymal cells characterized by the structure of the synovial intima, playing a crucial role in both the initiation and progression of RA. Objective: In this study, we evaluated the effects of melittin on the viability and apoptosis of FLS isolated from patients with RA. Methods: Cell viability was determined using CCK-8 assays; apoptosis was evaluated by flow cytometry, and the expression levels of apoptosis-related proteins (caspase-3, caspase-9, BAX, and Bcl-2) were also determined. To explore whether melittin alters inflammatory processes in RA-FLS, IL-1β levels were determined using an enzyme-linked immunosorbent assay (ELISA). Furthermore, we performed GFP-LC3 punctate fluorescence dot assays and western blotting (for LC3, ATG5, p62, and Beclin 1) to assess autophagy in RA-FLS. Results: Our results show that melittin can significantly impair viability, promote apoptosis and autophagy, and inhibit IL-1β secretion in RA-FLS. Conclusion: Melittin may be useful in preventing damage to the joints during accidental local stimulation.

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Amiloride Alleviates Neurological Deficits Following Transient Global Ischemia and Engagement of Central IL-6 and TNF-α Signal

Current Molecular Medicine ◽

10.2174/1566524019666190704100444 ◽

2019 ◽

Vol 19 (8) ◽

pp. 597-604

Author(s):

Li Pang ◽

Shouqin Ji ◽

Jihong Xing

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Caspase 3 ◽

Global Ischemia ◽

Neurological Deficits ◽

Global Cerebral Ischemia ◽

Caspase 9 ◽

Tnf Α ◽

The Central Nervous System ◽

Transient Global Ischemia

Background: Central pro-inflammatory cytokine (PIC) signal is involved in neurological deficits after transient global ischemia induced by cardiac arrest (CA). The present study was to examine if blocking acid sensing ion channels (ASICs) using amiloride in the Central Nervous System can alleviate neurological deficits after the induction of CA and further examine the participation of PIC signal in the hippocampus for the effects of amiloride. Methods: CA was induced by asphyxia and then cardiopulmonary resuscitation was performed in rats. Western blot analysis and ELISA were used to determine the protein expression of ASIC subunit ASIC1 in the hippocampus, and the levels of PICs. As noted, it is unlikely that this procedure is clinically used although amiloride and other pharmacological agents were given into the brain in this study. Results: CA increased ASIC1 in the hippocampus of rats in comparison with control animals. This was associated with the increase in IL-1β, IL-6 and TNF-α together with Caspase-3 and Caspase-9. The administration of amiloride into the lateral ventricle attenuated the upregulation of Caspase-3/Caspase-9 and this further alleviated neurological severity score and brain edema. Inhibition of central IL-6 and TNF-α also decreased ASIC1 in the hippocampus of CA rats. Conclusion: Transient global ischemia induced by CA amplifies ASIC1a in the hippocampus likely via PIC signal. Amiloride administered into the Central Nervous System plays a neuroprotective role in the process of global ischemia. Thus, targeting ASICs (i.e., ASIC1a) is suggested for the treatment and improvement of CA-evoked global cerebral ischemia.

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The Anti-Proliferative Activity of Anisosciadone: A New Guaiane Sesquiterpene from Anisosciadium lanatum

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520619666190308112732 ◽

2019 ◽

Vol 19 (9) ◽

pp. 1114-1119 ◽

Cited By ~ 2

Author(s):

Ahmed A. Mahmoud ◽

Wael M. El-Sayed

Keyword(s):

Anticancer Agents ◽

Antiproliferative Activity ◽

Molecular Mechanisms ◽

Caspase 3 ◽

Chemical Constituents ◽

Spectroscopic Techniques ◽

Significant Activity ◽

Caspase 9 ◽

P53 Expression ◽

Expression And Activity

Background: The increase in cancer rate and the development of resistant tumors require a continuous search for new anticancer agents. Aims: This study aimed to analyze and identify the chemical constituents of Anisosciadium lanatum, and to investigate the antiproliferative activity of the identified constituents against various human cell lines (HepG2, MCF7, HT29, A549, and PC3) along with the possible molecular mechanisms involved. Methods: The structure of the isolated compounds was determined by spectroscopic techniques including HRFABMS, GC-MS, IR, and 400 MHz 1D and 2D NMR analyses (1H, 13C NMR, DEPT, 1H-1H COSY, HMQC, HMBC and NOESY). The antiproliferative activity and IC50 value of the isolated compounds were measured and compared to doxorubicin. Results: A new guaiane sesquiterpene containing a rare epoxide structural element, 10β,11β−epoxy−1α,4β,5β,7αΗ- guaiane-9-one, anisosciadone (1), and stigmasterol (2) have been isolated from the plant. Anisosciadone (1) showed a significant antiproliferative activity against liver, colon, and lung cells only, while stigmasterol (2) had a significant activity against liver, colon, and breast cells. Both 1 and 2 caused no cytotoxicity to normal fibroblasts. Anisosciadone elevated the expression and activity of Caspase 3 as well as p53 expression without affecting Caspase 9 in HepG2 cells. It also caused ~ 50% downregulation in cdk1 expression. Conclusion: Taken together, anisosciadone was specific in action against cancer cells and induced apoptosis in liver cells. It also has a unique feature by elevating the expression and activity of Caspase 3 without affecting the initiator Caspase 9. Therefore, anisosciadone deserves more investigation as a targeted therapy for cancer.

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Anticancer Activity of Platinum (II) Complex with 2-Benzoylpyridine by Induction of DNA Damage, S-Phase Arrest, and Apoptosis

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520619666191112114340 ◽

2020 ◽

Vol 20 (4) ◽

pp. 504-517

Author(s):

Yu-Lan Li ◽

Xin-Li Gan ◽

Rong-Ping Zhu ◽

Xuehong Wang ◽

Duan-Fang Liao ◽

...

Keyword(s):

Dna Damage ◽

B Cell ◽

Anticancer Activity ◽

Cancer Cells ◽

Hepg2 Cells ◽

Caspase 3 ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

S Phase ◽

Caspase 9

Objective: To overcome the disadvantages of cisplatin, numerous platinum (Pt) complexes have been prepared. However, the anticancer activity and mechanism of Pt(II) complexed with 2-benzoylpyridine [Pt(II)- Bpy]: [PtCl2(DMSO)L] (DMSO = dimethyl sulfoxide, L = 2-benzoylpyridine) in cancer cells remain unknown. Methods: Pt(II)-Bpy was synthesized and characterized by spectrum analysis. Its anticancer activity and underlying mechanisms were demonstrated at the cellular, molecular, and in vivo levels. Results: Pt(II)-Bpy inhibited tumor cell growth, especially HepG2 human liver cancer cells, with a halfmaximal inhibitory concentration of 9.8±0.5μM, but with low toxicity in HL-7702 normal liver cells. Pt(II)- Bpy induced DNA damage, which was demonstrated through a marked increase in the expression of cleavedpoly (ADP ribose) polymerase (PARP) and gamma-H2A histone family member X and a decrease in PARP expression. The interaction of Pt(II)-Bpy with DNA at the molecular level was most likely through an intercalation mechanism, which might be evidence of DNA damage. Pt(II)-Bpy initiated cell cycle arrest at the S phase in HepG2 cells. It also caused severe loss of the mitochondrial membrane potential; a decrease in the expression of caspase-9 and caspase-3; an increase in reactive oxygen species levels; the release of cytochrome c and apoptotic protease activation factor; and the activation of caspase-9 and caspase-3 in HepG2 cells, which in turn resulted in apoptosis. Meanwhile, changes in p53 and related proteins were observed including the upregulation of p53, the phosphorylation of p53, p21, B-cell lymphoma-2-associated X protein, and NOXA; and the downregulation of B-cell lymphoma 2. Moreover, Pt(II)-Bpy displayed marked inhibitory effects on tumor growth in the HepG2 nude mouse model. Conclusion: Pt(II)-Bpy is a potential candidate for cancer chemotherapy.

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