Cadmium promotes the binding and centrosomal translocation of CCDC85C and PLK4 via ROS-GCLM pathway to trigger centrosome amplification in colon cancer cells.

Cadmium (Cd) is a prevalent heavy metal contaminant that can cause centrosome amplification (CA) and cancer. Since CA can initiate tumorigenesis, it is plausible that cadmium initiates tumorigenesis via CA. The present study investigated the signaling pathways underlying CA by Cd.

Advanced glycation end products initiate the mutual promoting cycle between centrosome amplification and the release of inflammatory cytokines in human vascular endothelial cells.

Inflammation is implicated in the development of diabetic complications including vascular pathology. Centrosome is known to play a role in cell secretion. We have reported that diabetes can trigger centrosome amplification (CA).

Hexavalent chromium causes centrosome amplification by inhibiting the binding between TMOD2 and NPM2.

Background: Hexavalent chromium can promote centrosome amplification (CA) as well as tumorigenesis. Since CA can lead to tumorigenesis, it is plausible that the chromium promotes the development of cancer via CA. In the present study, we investigated the signaling pathways of the chromium-induced CA.

Toxic effects of maternal cadmium exposure on the metabolism and transport system of amino acids in the maternal livers.

Fetal growth restriction (FGR) is one of the most common obstetric diseases, and affects approximately 10 % of all pregnancies worldwide. Maternal cadmium (Cd) exposure is one of the factors that may increase the risk of the development of FGR. However, its underlying mechanisms remain largely unknown.

The novel antitumor compound clinopodiside A induces cytotoxicity autophagy mediated by the signaling of BLK and RasGRP2 in T24 bladder cancer cells.

In the study, we investigated the anti-cancer effect of clinopodiside A and the underlying mechanisms using T24 bladder cancer cells as an experimental model. We found that the compound inhibited the growth of the bladder cancer cells and in a in a concentration- and dose-dependent manner, respectively, which showed a combinational effect when used together with cisplatin. In the bladder cancer cells, clinopodiside A caused autophagy, which was mediated by the signaling of BLK and RasGRP2, independently.

The binding between NPM and H2B proteins signals for the diabetes-associated centrosome amplification.

Diabetes not only increases the risk for cancer but also promotes cancer metastasis. Centrosome amplification (CA) is sufficient to initiate tumorigenesis and can enhance the invasion potential of cancer cells. We have reported that diabetes can induce CA, with diabetic pathophysiological factors as the triggers, which involves the signaling of nucleophosmin (NPM).

Hexavalent chromium induces centrosome amplification through ROS-ATF6-PLK4 pathway in colon cancer cells.

Centrosome amplification (CA) refers to a numerical increase in centrosomes resulting in cells with more than two centrosomes. CA has been shown to initiate tumorigenesis and increase the invasive potential of cancer cells in genetically modified experimental models. Hexavalent chromium is a recognized carcinogen that causes CA and tumorigenesis as well as promotes cancer metastasis.

Legacy effect of high glucose on promoting survival of HCT116 colorectal cancer cells by reducing endoplasmic reticulum stress response.

Patients with diabetes have increased risk of cancer and poor response to anti-cancer treatment. Increased protein synthesis is associated with endoplasmic reticulum (ER) stress which can trigger the unfolded protein response (UPR) to restore homeostasis, failure of which can lead to dysregulated cellular growth. We hypothesize that hyperglycemia may have legacy effect in promoting survival of cancer cells through dysregulation of UPR.

Binding between ROCK1 and DCTN2 triggers diabetes‑associated centrosome amplification in colon cancer cells.

Type 2 diabetes increases the risk various types of cancer and is associated with a poor prognosis therein. There is also evidence that the disease is associated with cancer metastasis. Centrosome amplification can initiate tumorigenesis with metastasis and increase the invasiveness of cancer cells .

Centrosome amplification in cancer and cancer-associated human diseases.

Accumulated evidence from genetically modified cell and animal models indicates that centrosome amplification (CA) can initiate tumorigenesis with metastatic potential and enhance cell invasion. Multiple human diseases are associated with CA and carcinogenesis as well as metastasis, including infection with oncogenic viruses, type 2 diabetes, toxicosis by environmental pollution and inflammatory disease. In this review, we summarize (1) the evidence for the roles of CA in tumorigenesis and tumor cell invasion; (2) the association between diseases and carcinogenesis as well as metastasis; (3) the current knowledge of CA in the diseases; and (4) the signaling pathways of CA.

Periplogenin Activates ROS-ER Stress Pathway to Trigger Apoptosis via BIP-eIF2α- CHOP and IRE1α-ASK1-JNK Signaling Routes.

Background: Periplogenin (PPG), a natural compound isolated from traditional Chinese herb Cortex Periplocae, has been reported to possess anti-inflammatory and anti-cancer properties.

Objective: The present study aims to investigate the antitumor effects of PPG and the underlying mechanism in human colorectal cancer cells.

Methods: The inhibition of cell growth in vitro was assessed by MTT assay.

Resveratrol attenuates diabetes-associated cell centrosome amplification via inhibiting the PKCα-p38 to c-myc/c-jun pathway.

Type 2 diabetes increases the risk for cancer. Centrosome amplification can initiate tumorigenesis. We have described that type 2 diabetes increases the centrosome amplification of peripheral blood mononuclear cells, with high glucose, insulin, and palmitic acid as the triggers, which suggests that centrosome amplification is a candidate biological mechanism linking diabetes to cancer.

Identification and profiling of microRNAs responsive to cadmium toxicity in hepatopancreas of the freshwater crab .

Background: Cadmium (Cd) is a ubiquitous environmental toxicant for aquatic animals. The freshwater crab, (), is a useful model for monitoring Cd exposure since it is widely distributed in sediments whereby it tends to accumulate several toxicants, including Cd. In the recent years, the toxic effects of Cd in the hepatopancreas of have been demonstrated by a series of biochemical analysis and ultrastructural observations as well as the deep sequencing approaches and gene expression profile analysis.

Secreted Wnt6 mediates diabetes-associated centrosome amplification via its receptor FZD4.

We recently published that type 2 diabetes promotes cell centrosome amplification via upregulation of Rho-associated protein kinase 1 (ROCK1) and 14-3-3 protein-σ (14-3-3σ). This study further investigates the molecular mechanisms underlying diabetes-associated centrosome amplification. We found that treatment of cells with high glucose, insulin, and palmitic acid levels increased the intracellular and extracellular protein levels of Wingless-type MMTV integration site family member 6 (Wnt6) as well as the cellular level of β-catenin.

Downregulations of placental fatty acid transporters during cadmium-induced fetal growth restriction.

Cadmium (Cd) is one of the environmental pollutants, which has multiple toxic effects on fetuses and placentas. Placental fatty acid (FA) uptake and transport are critical for the fetal and placental development. We aimed to analyze the triglyceride (TG) level, the expression patterns of several key genes involved in FA uptake and transport, and the molecular mechanisms for the altered gene expressions in placentas in response to Cd treatment.

PPARγ promotes diabetes-associated centrosome amplification via increasing the expression of SKA1 directly at the transcriptional level.

We have recently published that type 2 diabetes can induce cell centrosome amplification due to the action of high glucose, palmitic acid, and insulin, and ROCK1 and 14-3-3σ are signal mediators. In this study, we further investigated the molecular mechanisms of the centrosome amplification in colon cancer HCT116 cells. Treatment of the cells with high glucose, palmitic acid, and insulin increased the expression of peroxisome proliferator-activated receptor γ (PPARγ) as well as the spindle and kinetochore associated protein 1 (SKA1), knockdown of each of which resulted in the inhibition of the treatment-triggered centrosome amplification.

Cadmium induces cell centrosome amplification via reactive oxygen species as well as endoplasmic reticulum stress pathway.

There is evidence that cadmium can initiate carcinogenesis. However, the underlying mechanisms remain unknown. There is also evidence that moderate centrosome amplification can initiate tumorigenesis.

Hsp74/14-3-3σ Complex Mediates Centrosome Amplification by High Glucose, Insulin, and Palmitic Acid.

It has been reported recently that type 2 diabetes promotes centrosome amplification via 14-3-3σ/ROCK1 complex. In the present study, 14-3-3σ interacting proteins are characterized and their roles in the centrosome amplification by high glucose, insulin, and palmitic acid are investigated. Co-immunoprecipitation in combination with MS analysis identified 134 proteins that interact with 14-3-3σ, which include heat shock 70 kDa protein 4 (Hsp74).

PCNA and JNK1-Stat3 pathways respectively promotes and inhibits diabetes-associated centrosome amplification by targeting at the ROCK1/14-3-3σ complex in human colon cancer HCT116 cells.

We have recently reported that type 2 diabetes promotes centrosome amplification via enhancing the expression, biding, and centrosome translocation of rho-associated coiled-coil containing protein kinase 1 (ROCK1)/14-3-3σ complex in HCT116 cells. In the functional proteomic study, we further investigated the molecular pathways underlying the centrosome amplification using HCT116 cells. We found that treatment of HCT116 cells with high glucose, insulin, and palmitic acid triggered the centrosome amplification and increased the expressions of proliferating cell nuclear antigen (PCNA), nucleophosmin (NPM), and 14-3-3σ.

Advanced Glycation End Products Increase MDM2 Expression via Transcription Factor KLF5.

Type 2 diabetes increases the risk for all-site cancers including colon cancer. Diabetic patients present typical pathophysiological features including an increased level of advanced glycation end products (AGEs), which comes from a series of nonenzymatic reactions between sugars and biological macromolecules, positively associated with the occurrence of diabetic complications. MDM2 is an oncogene implicated in cancer development.

Functional proteomic analysis revels that the ethanol extract of Annona muricata L. induces liver cancer cell apoptosis through endoplasmic reticulum stress pathway.

Ethnopharmacological Relevance: Annona muricata L. is used to treat cancer in some countries. Extracts of Annona muricata have been shown to cause apoptosis of various cancer cells in vitro, and inhibit tumor growth in vivo in animal models.

Overcome Cancer Cell Drug Resistance Using Natural Products.

Chemotherapy is one of the major treatment methods for cancer. However, failure in chemotherapy is not uncommon, mainly due to dose-limiting toxicity associated with drug resistance. Management of drug resistance is important towards successful chemotherapy.

Evidence for DNA damage as a biological link between diabetes and cancer.

Objective: This review examines the evidence that: Diabetes is a state of DNA damage; pathophysiological factors in diabetes can cause DNA damage; DNA damage can cause mutations; and DNA mutation is linked to carcinogenesis.

Data Sources: We retrieved information from the PubMed database up to January, 2014, using various search terms and their combinations including DNA damage, diabetes, cancer, high glucose, hyperglycemia, free fatty acids, palmitic acid, advanced glycation end products, mutation and carcinogenesis.

Study Selection: We included data from peer-reviewed journals and a textbook printed in English on relationships between DNA damage and diabetes as well as pathophysiological factors in diabetes.

Additive effect of aldose reductase Z-4 microsatellite polymorphism and glycaemic control on cataract development in type 2 diabetes.

Aims: To examine the additive effect of the z-4 microsatellite polymorphism of aldose reductase gene (ALR2) and glycaemic control on risk of cataract in a prospective cohort of Chinese type 2 diabetic patients.

Methods: The (CA)n microsatellite polymorphism of ALR2 was determined using PCR followed by capillary gel electrophoresis. Cataract was defined by presence of lens opacity on direct ophthalmoscopy or history of cataract surgery.

Proteomic identification of chaperonin-containing tail-less complex polypeptide-1 gamma subunit as a p53-responsive protein in colon cancer cells.

We recently reported that functional loss of p53 altered the responses of human HCT116 colon cancer cells to apoptosis triggers. To examine the molecular basis underlying the differential responses to drug treatment in the cancer cells, we performed a proteomic analysis in order to compare the protein expressions between human colon cancer cells with and those without p53 (p53(+/+) and p53(-/-)) respectively. We identified two isoelectric variants of the chaperonin-containing tail-less complex polypeptide-1 gamma subunit (TCP-1γ) from the cells, and confirmed that the two isoelectric variants were phosphorylated at tyrosine residue(s).