The involvement and possible targeting of cardiolipins degradation and disturbed linoleic acid metabolism in cardiac atrophy under cancer cachexia.

Cardiac atrophy is one of the critical characteristics of cancer cachexia though its mechanisms had not been fully clarified. In the present study, to study the mechanisms of cardiac atrophy in cancer cachexia and search for possible drug targets, cancer cachexia mice bearing C26 colon tumor cells and cultured H9c2 cardiomyocytes induced with simulated cancer cachexia injuries were used as in vivo and in vitro model, respectively. Results of both spatial metabolomics and LC-MS non-targeted metabolomics analysis of heart tissues suggested the disturbance of glycerophospholipid and fatty acid metabolism in the cancer cachexia hearts.

Carnosol ameliorated cancer cachexia-associated myotube atrophy by targeting P5CS and its downstream pathways.

Carnosol exhibited ameliorating effects on muscle atrophy of mice developed cancer cachexia in our previous research. Here, the ameliorating effects of carnosol on the C2C12 myotube atrophy result from simulated cancer cachexia injury, the conditioned medium of the C26 tumor cells or the LLC tumor cells, were observed. To clarify the mechanisms of carnosol, the possible direct target proteins of carnosol were searched using DARTS (drug affinity responsive target stability) assay and then confirmed using CETSA (cellular thermal shift assay).

GDF-15 in tumor-derived exosomes promotes muscle atrophy via Bcl-2/caspase-3 pathway.

Tumor-derived exosomes are emerging mediators of cancer cachexia, a kind of multifactorial syndrome characterized by serious loss of skeletal muscle mass and function. Our previous study had showed that microRNAs in exosomes of C26 colon tumor cells were involved in induction of muscle atrophy. Here, we focus on studying proteins in tumor-derived exosomes which might also contribute to the development of cancer cachexia.

Bile acid metabolism dysregulation associates with cancer cachexia: roles of liver and gut microbiome.

Background: Cancer cachexia is a multifactorial metabolic syndrome in which bile acid (BA) metabolism might be involved. The aim of the present study was to clarify the contribution of liver and gut microbiota to BA metabolism disturbance in cancer cachexia and to check the possibility of targeting BA metabolism using agents such as tauroursodeoxycholic acid (TUDCA) for cancer cachexia therapy.

Methods: The BA profiles in liver, intestine, and serum of mice with cancer cachexia induced by inoculation of colon C26 tumour cells were analysed using metabolomics methods and compared with that of control mice.

miR-92b-3p Regulates Cell Cycle and Apoptosis by Targeting , Thereby Affecting the Sensitivity of Colorectal Cancer Cells to Chemotherapeutic Drugs.

Colorectal cancer (CRC) is the third most common malignant tumor in the world and the second leading cause of cancer death. Multidrug resistance (MDR) has become a major obstacle in the clinical treatment of CRC. The clear molecular mechanism of MDR is complex, and miRNAs play an important role in drug resistance.

Cancer-derived exosome miRNAs induce skeletal muscle wasting by Bcl-2-mediated apoptosis in colon cancer cachexia.

Cancer cachexia is a kind of whole-body metabolic disorder syndrome accompanied by severe wasting of muscle tissue in which cancer exosomes may be involved. Analysis of clinical samples showed that the serum exosome concentrations were correlated with the development of cancer cachexia. Exosomes secreted by C26 cells could decrease the diameter of C2C12 myotubes and decrease mouse muscle strength and tibialis anterior (TA) muscle weight .

Binding of RNA m6A by IGF2BP3 triggers chemoresistance of HCT8 cells via upregulation of ABCB1.

The overexpression of ATP-binding cassette transporters subfamily B member 1 (ABCB1) is known to be the primary trigger of multidrug resistance (MDR) in colorectal cancer (CRC), leading to chemotherapy failure. However, factors that regulate chemoresistance in CRC cells are largely unknown. To identify proteins involved in MDR in CRC, we used proteomics and transcriptomics approaches to analyze HCT8/T cells and parental HCT8 cells.

NEK2 promotes proliferation, migration and tumor growth of gastric cancer cells via regulating KDM5B/H3K4me3.

The mechanisms of how Never in Mitosis (NIMA) Related Kinase 2 (NEK2) coordinates altered signaling to malignant gastric cancer (GC) transformation remain unclear. Overexpression of NEK2 and KDM5B were observed in GC cell lines with high sensitivity to NEK2 inhibitors. Here we investigated the biological behaviors of NEK2 and the possible mechanisms of regulative effects of NEK2 on KDM5B in GC cell lines both and .

Pyrrolidine Dithiocarbamate (PDTC) Attenuates Cancer Cachexia by Affecting Muscle Atrophy and Fat Lipolysis.

Cancer cachexia is a kind of whole body metabolic disorder syndrome accompanied with severe wasting of muscle and adipose tissue. NF-κB signaling plays an important role during skeletal muscle atrophy and fat lipolysis. As an inhibitor of NF-κB signaling, Pyrrolidine dithiocarbamate (PDTC) was reported to relieve cancer cachexia; however, its mechanism remains largely unknown.

Agglutinin isolated from Arisema heterophyllum Blume induces apoptosis and autophagy in A549 cells through inhibiting PI3K/Akt pathway and inducing ER stress.

Arisaema heterophyllum Blume is one of the three medicinal plants known as traditional Chinese medicine Rhizoma Arisaematis (RA). RA has been popularly used to treat patients with convulsions, inflammation, and cancer for a long time. However, the underlying mechanisms for RA effects are still unclear.

Nano-LC-ESI MS/MS analysis of proteins in dried sea dragon Solenognathus hardwickii and bioinformatic analysis of its protein expression profiling.

The sea dragon Solenognathus hardwickii has long been used as a traditional Chinese medicine for the treatment of various diseases, such as male impotency. To gain a comprehensive insight into the protein components of the sea dragon, shotgun proteomic analysis of its protein expression profiling was conducted in the present study. Proteins were extracted from dried sea dragon using a trichloroacetic acid/acetone precipitation method and then separated by SDS-PAGE.

Knockdown of Apolipoprotein E Enhanced Sensitivity of Hep3B Cells to Cardiac Steroids via Regulating Na+/K+-ATPase Signalosome.

This study compared the sensitivity of human hepatoma Hep3B, SK-HEP-1, SMMC-7721, and BEL-7402 cells to cardiac steroids, including bufalin (BF), a bufalin derivative (BF211), ouabain (OUA), and digitoxin (DIG). Hep3B cells exhibited relatively low sensitivity to cardiac steroids. Expression levels of subunits of Na/K-ATPase were high in Hep3B cells.

A Novel Bufalin Derivative Exhibited Stronger Apoptosis-Inducing Effect than Bufalin in A549 Lung Cancer Cells and Lower Acute Toxicity in Mice.

BF211 is a synthetic molecule derived from bufalin (BF). The apoptosis-inducing effect of BF211 was stronger than that of BF while the acute toxicity of BF211 was much lower than that of BF. BF211 exhibited promising concentration-dependent anti-cancer effects in nude mice inoculated with A549 cells in vivo.

Proteasome Inhibition Contributed to the Cytotoxicity of Arenobufagin after Its Binding with Na, K-ATPase in Human Cervical Carcinoma HeLa Cells.

Although the possibility of developing cardiac steroids/cardiac glycosides as novel cancer therapeutic agents has been recognized, the mechanism of their anticancer activity is still not clear enough. Toad venom extract containing bufadienolides, which belong to cardiac steroids, has actually long been used as traditional Chinese medicine in clinic for cancer therapy in China. The cytotoxicity of arenobufagin, a bufadienolide isolated from toad venom, on human cervical carcinoma HeLa cells was checked.

Bufalin derivative BF211 inhibits proteasome activity in human lung cancer cells in vitro by inhibiting β1 subunit expression and disrupting proteasome assembly.

Aim: Bufalin is one of the active components in the traditional Chinese medicine ChanSu that is used to treat arrhythmia, inflammation and cancer. BF211 is a bufalin derivative with stronger cytotoxic activity in cancer cells. The aim of this study was to identify the putative target proteins of BF211 and the signaling pathways in cancer cells.

Possible target-related proteins and signal network of bufalin in A549 cells suggested by both iTRAQ-based and label-free proteomic analysis.

Bufalin (BF) exhibited antiproliferation and antimigration effects on human A549 lung cancer cells. To search its target-related proteins, protein expression profiles of BF-treated and control cells were compared using two quantitative proteomic methods, iTRAQ-based and label-free proteomic analysis. A total of 5428 proteins were identified in iTRAQ-based analysis while 6632 proteins were identified in label-free analysis.

Protective Effects of Scutellarin on Human Cardiac Microvascular Endothelial Cells against Hypoxia-Reoxygenation Injury and Its Possible Target-Related Proteins.

Scutellarin (SCU) is one of the main components of traditional Chinese medicine plant Erigeron breviscapus (Vant.) Hand.-Mazz.

Inhibition on Proteasome β1 Subunit Might Contribute to the Anti-Cancer Effects of Fangchinoline in Human Prostate Cancer Cells.

Fangchinoline is a bisbenzylisoquinoline alkaloid isolated from Radix Stephaniae tetrandrae S. Moore. Fangchinoline and its structure analogue, tetrandrine, exhibited direct binding affinity with recombinant human proteasome β1 subunit and also inhibited its activity in vitro.

Proteomic Analysis Revealed the Important Role of Vimentin in Human Cervical Carcinoma HeLa Cells Treated With Gambogic Acid.

Gambogic acid (GA) is an anticancer agent in phase IIb clinical trial in China. In HeLa cells, GA inhibited cell proliferation, induced cell cycle arrest at G2/M phase and apoptosis, as showed by results of MTT assay and flow cytometric analysis. Possible target-related proteins of GA were searched using comparative proteomic analysis (2-DE) and nine proteins at early (3 h) stage together with nine proteins at late (24 h) stage were found.

Proteomic and bioinformatic analyses of possible target-related proteins of gambogic acid in human breast carcinoma MDA-MB-231 cells.

Gambogic acid (GA) is an anticancer agent in phase ‖b clinical trial in China but its mechanism of action has not been fully clarified. The present study was designed to search the possible target-related proteins of GA in cancer cells using proteomic method and establish possible network using bioinformatic analysis. Cytotoxicity and anti-migration effects of GA in MDA-MB-231 cells were checked using MTT assay, flow cytometry, wound migration assay, and chamber migration assay.

[Study on proteomics of Hela cell apoptosis in bufalin-induced human cervical carcinoma].

Objective: To seek possible effect targets of bufalin in HeLa cells by studying the impact of bufalin on cell protein expression profile after treatment on human cervical carcinoma cell lines HeLa.

Method: Bufalin's ICs0was measured by MTr assay. The apoptosis of cells was observed by FCM (flow cytometry) and Hoechst 33342 staining assay.

[Expression, purification of proteasome subunit PSMB1 and application in screening of possible proteasome inhibitors].

Proteasome is a multi-subunit protease complex in eukaryocytes, and plays an important role in ubiquitin-proteosome pathway. Recombinant proteasome can be used to screen proteasome inhibitors. In this study, recombinant plasmid of pET28a-PSMB1 was constructed by inserting human proteasome catalytic subunit (PSMB1) cDNA (726 bp) into the prokaryotic expression vector pET28a(+), and transforming the plasmid into E.

Paraptosis accompanied by autophagy and apoptosis was induced by celastrol, a natural compound with influence on proteasome, ER stress and Hsp90.

In the present study, we found that celastrol, a natural compound with well-known apoptosis-inducing effect, could also induce paraptosis-like cytoplasmic vacuolization in cancer cell lines including HeLa cells, A549 cells and PC-3 cells derived from cervix, lung and prostate, respectively. Further study using HeLa cells indicated that the vacuoles induced by celastrol might be derived from dilation of endoplasmic reticulum. And, in celastrol-treated cells, markers of autophagy such as transformation of microtubule-associated protein 1 light chain 3 (LC3)I to LC3II and LC3 punctates formation were identified.

Clarifying the signal network of salvianolic acid B using proteomic assay and bioinformatic analysis.

Salvianolic acid B (SB) is a natural compound with protective effect against ischemia-reperfusion heart injury. However, the signal network of SB including both direct target proteins and downstream signal-related proteins has not been clarified. In the present study, epidermal growth factor receptor (EGFR) was predicted to be the most possible direct protein target of SB by INVDOCK, a ligand-protein inverse-docking algorithm.

Cytotoxicity of 9,11-dehydroergosterol peroxide isolated from Ganoderma lucidum and its target-related proteins.

The cytotoxicty of 9,11-dehydroergosterol peroxide (DHEP) isolated from the fruiting bodies of Ganoderma lucidum on HeLa cells was studied. DHEP treatment for 48 h inhibited the proliferation of HeLa human cervical carcinoma cells with an IC50-value of 8.58 +/- 0.