Potential role of mitochondrial damage and S9 mixture including metabolic enzymes in ZnO nanoparticles-induced oxidative stress and genotoxicity in Chinese hamster lung (CHL/IU) cells.

The present study was designed to examine genotoxicity induced by 10-40 nm zinc oxide (ZnO) nanoparticles using the in vitro system. The frequency of micronuclei was significantly increased in a dose-dependent manner when cultured Chinese hamster lung (CHL/IU) cells were exposed to ZnO nanoparticles for 24, 48 and 72 h in the continuous treatment method. The maximal frequency of micronuclei was observed in exposure of CHL/IU cells to ZnO nanoparticles at a concentration of 125 μM.

Three Combined Treatments, a Novel HDAC Inhibitor OBP-801/YM753, 5-Fluorouracil, and Paclitaxel, Induce G₂ Phase Arrest Through the p38 Pathway in Human Ovarian Cancer Cells.

Ovarian cancer is the most lethal disease among gynecological malignancies. More effective therapy is required to counter high recurrence rates and chemotherapy resistance. We investigated the efficacy and molecular mechanisms of three combined treatments (TCTs)-a novel histone deacetylase (HDAC) inhibitor OBP-801/YM753, 5-fluorouracil (5-FU), and paclitaxel (PTX)-in human ovarian cancer SKOV-3 and OVCAR-3 cells.

[Corrigendum] Brassinin induces G1 phase arrest through increase of p21 and p27 by inhibition of the phosphatidylinositol 3-kinase signaling pathway in human colon cancer cells.

After the publication of the article, the authors noted that they had made the following errors. In Fig. 5B, total PDK1 is incorrect in the published paper.

The alkaloid emetine sensitizes ovarian carcinoma cells to cisplatin through downregulation of bcl-xL.

Cisplatin and its platinum derivatives are first-line chemotherapeutic agents in the treatment of ovarian cancer. However, chemoresistance is the leading cause of therapeutic failure and is responsible for the poor overall survival rate. Here, we describe that emetine, a natural alkaloid used as an anti-amoebiasis drug, sensitized ovarian carcinoma cells to apoptosis induced by cisplatin.

Combination of a novel HDAC inhibitor OBP-801/YM753 and a PI3K inhibitor LY294002 synergistically induces apoptosis in human endometrial carcinoma cells due to increase of Bim with accumulation of ROS.

Objective: In most endometrial carcinoma, it has been observed that the PI3K/Akt pathway is abnormally accelerated in association with mutations in PIK3CA and PTEN. The present study aimed to examine the combined effect of a novel histone deacetylase (HDAC) inhibitor OBP-801/YM753 and a PI3K inhibitor LY294002 against human endometrial carcinoma cells.

Methods: The effects of OBP-801/YM753 and LY294002 on the growth of human endometrial carcinoma HEC-1A cells were examined using WST-8 and colony formation assays.

Dehydrozingerone, a structural analogue of curcumin, induces cell-cycle arrest at the G2/M phase and accumulates intracellular ROS in HT-29 human colon cancer cells.

Dehydrozingerone (1) is a pungent constituent present in the rhizomes of ginger (Zingiber officinale) and belongs structurally to the vanillyl ketone class. It is a representative of half the chemical structure of curcumin (2), which is an antioxidative yellow pigment obtained from the rhizomes of turmeric (Curcuma longa). Numerous studies have suggested that 2 is a promising phytochemical for the inhibition of malignant tumors, including colon cancer.

p53 inactivation upregulates p73 expression through E2F-1 mediated transcription.

While p73 overexpression has been associated with increased apoptosis in cancer tissues, p73 overexpressing tumors appear to be of high grade malignancy. Why this putative tumor suppressor is overexpressed in cancer cells and what the function of overexpressed p73 is in breast cancers are critical questions to be addressed. By investigating the effect of p53 inactivation on p73 expression, we found that both protein and mRNA levels of TAp73 were increased in MCF-7/p53siRNA cells, MCF-7/p53mt135 cells and HCT-116/p53-/- cells, as compared to wild type control, suggesting that p53 inactivation by various forms upregulates p73.

Brassinin induces G1 phase arrest through increase of p21 and p27 by inhibition of the phosphatidylinositol 3-kinase signaling pathway in human colon cancer cells.

The phosphatidylinositol 3-kinase (PI3K) signaling pathway is activated in a broad spectrum of human cancers, including colon cancer. The natural product brassinin is a type of indole compound derived from cruciferous vegetables, and has been shown to have anti-proliferative effects against cancer for both in vivo and in vitro models. Here, we show for the first time that brassinin inhibits cell growth in human colon cancer cells by arresting the cell cycle at the G1 phase via inhibition of the PI3K signaling pathway.

Polymorphisms in promoter sequences of the p15 ( INK4B ) and PTEN genes of normal Japanese individuals.

Gene promoter regions of p15(INK4B), a cyclin-dependent kinase inhibitor, and phosphatase and tensin homolog (PTEN), a dual-function protein and lipid phosphatase, interact with regulatory factors for gene transcription and methylation. Normal individuals exhibit sequence polymorphisms in these regulatory genes. We isolated genomic DNA from whole blood of healthy Japanese individuals and sequenced promoter regions of the p15 ( INK4B ) and PTEN genes.

Histone deacetylase inhibitors and 15-deoxy-Delta12,14-prostaglandin J2 synergistically induce apoptosis.

Purpose: The clinically relevant histone deacetylase inhibitors (HDI) valproic acid (VPA) and suberoylanilide hydroxamic acid exert variable antitumor activities but increase therapeutic efficacy when combined with other agents. The natural endogenous ligand of peroxisome proliferator-activated receptor gamma 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) is a potent antineoplastic agent. Therefore, we investigated whether these HDIs in combination with 15d-PGJ(2) could show synergistic antitumor activity in colon cancer DLD-1 cells.

Cucurbitacin B induces G2 arrest and apoptosis via a reactive oxygen species-dependent mechanism in human colon adenocarcinoma SW480 cells.

Cucurbitacin B (cucB) is a triterpenoid constituent of Cucurbitaceae vegetables and a promising phytochemical for cancer prevention. However, the mechanism of anti-tumor activity of cucB remains unknown, especially in colon cancers. Here, we demonstrate for the first time that cucB inhibited growth of human colon cancer SW480 cells through a reactive oxygen species (ROS)-dependent mechanism.

A combination of indol-3-carbinol and genistein synergistically induces apoptosis in human colon cancer HT-29 cells by inhibiting Akt phosphorylation and progression of autophagy.

Background: The chemopreventive effects of dietary phytochemicals on malignant tumors have been studied extensively because of a relative lack of toxicity. To achieve desirable effects, however, treatment with a single agent mostly requires high doses. Therefore, studies on effective combinations of phytochemicals at relatively low concentrations might contribute to chemopreventive strategies.

Identification of JTP-70902, a p15(INK4b)-inductive compound, as a novel MEK1/2 inhibitor.

The INK4 family members p16(INK4a) and p15(INK4b) negatively regulate cell cycle progression by inhibition of cyclin-dependent kinase (CDK) 4/6. Loss of p16(INK4a) functional activity is frequently observed in tumor cells, and is thought to be one of the primary causes of carcinogenesis. In contrast, despite the biochemical similarity to p16(INK4a), the frequency of defects in p15(INK4b) was found to be lower than in p16(INK4a), suggesting that p15(INK4b)-inductive agents may be useful for tumor suppression.

ZD1839 induces p15INK4b and causes G1 arrest by inhibiting the mitogen-activated protein kinase/extracellular signal-regulated kinase pathway.

Inactivation of the retinoblastoma protein pathway is the most common abnormality in malignant tumors. We therefore tried to detect agents that induce the cyclin-dependent kinase inhibitor p15(INK4b) and found that ZD1839 (gefitinib, Iressa) could up-regulate p15(INK4b) expression. ZD1839 has been shown to inhibit cell cycle progression through inhibition of signaling pathways such as phosphatidylinositol 3'-kinase-Akt and mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) cascades.

Oct-1 is involved in the transcriptional repression of the p15(INK4b) gene.

p15(INK4b) functions as a tumor suppressor and implicated in cellular senescence. Here, we show that the Oct-1 binding site in the human p15(INK4b) gene promoter functions as a silencer. Oct-1 specifically interacts with this binding site in vitro and in vivo and SMRT and HDAC1 are present in the p15(INK4b) proximal promoter region.

A novel synthetic drug, LB-18, closely related to lembehyne-A derived from a marine sponge, induces caspase-independent cell death to human neuroblastoma cells.

Neuroblastoma is a common solid tumor of children that arises from the sympathetic nervous system. Much work has consequently focused on the possibility of inducing marked cell death in neuroblastoma, and the new effective drugs are required. We have newly synthesized LB-18, closely related to lembehyne A (LB-A), a polyacetylene derived from a kind of marine sponge.

Lysocellin, a metabolite of the novel drug 'alopestatin', induces G1 arrest and prevents cytotoxicity induced by etoposide.

We report here that lysocellin, a polyether antibiotic from a streptomycete, induces G1 phase arrest in human osteosarcoma MG63 cells. Lysocellin up-regulates p21WAF1/Cip1 and down-regulates cyclin D1 at the mRNA level. In addition, cyclin D1 is down-regulated by the proteasome-dependent signal pathway in MG63 cells.

Quercetin induces gadd45 expression through a p53-independent pathway.

Quercetin, a kind of flavonoid, is found in edible fruits and vegetables and has anti-tumorigenic activity. However, the mechanism of activity has not been elucidated. We show for the first time that gadd45 is a molecular target of quercetin, which inhibits growth of human cervical cancer HeLa cells.

Inhibitory effects of cancer cell proliferation by novel histone deacetylase inhibitors involve p21/WAF1 induction and G2/M arrest.

Two compounds were synthesized which have a structural component other than those of our new series histone deacetylase (HDAC) inhibitors to determine the structure-activity relationship. It was also examined whether the inhibitory effects on cancer cell proliferation by HDAC inhibitors involve p21/WAF1 induction and G(1) or G(2)/M arrest in p53-mutated MG63 human osteosarcoma cells as do other HDAC inhibitors. It was demonstrated that inhibitors with the 2-naphthylcarbonyl group and hydroxamic acid at both termimal sides as well as the phenylene component at the center of molecule markedly induce the p21/WAF1 protein by stimulating p21/WAF1 gene promoter activity.

Cancer prevention by antioxidants.

Various antioxidants in foods, such as phenolic compounds and carotenoids, were proven to have anticarcinogenic activity. In the case of carotenoids, the mixture of them was found to be very effective. In fact, the development of hepatoma in the high risk group of liver cancer, was significantly suppressed by the treatment with natural carotenoids mixture.

Apigenin induces cell cycle arrest and p21/WAF1 expression in a p53-independent pathway.

Apigenin, a common dietary flavonoid, has been shown to induce cell growth-inhibition and cell cycle arrest in many cancer cell lines. One important effect of apigenin is to increase the stability of the tumor suppressor p53 in normal cells. Therefore, apigenin is expected to play a large role in cancer prevention by modifying the effects of p53 protein.

Carotenoids in cancer chemoprevention.

Various natural carotenoids, besides beta-carotene, were proven to have anticarcinogenic activity, and some of them showed more potent activity than beta-carotene. Thus, these carotenoids (alpha-carotene, lutein, zeaxanthin, lycopene, beta-cryptoxanthin, fucoxanthin, astaxanthin, capsanthin, crocetin and phytoene), as well as beta-carotene, may be useful for cancer prevention. In the case of phytoene, the concept of 'bio-chemoprevention', which means biotechnology-assisted method for cancerchemoprevention, may be applicable.