Human papillomavirus type 16 E6 suppresses microRNA-23b expression in human cervical cancer cells through DNA methylation of the host gene C9orf3.

Oncogenic protein E6 of human papillomavirus type 16 (HPV-16) is believed to involve in the aberrant methylation in cervical cancer as it upregulates DNA methyltransferase 1 (DNMT1) through tumor suppressor p53. In addition, DNA demethylating agent induces the expression of one of the HPV-16 E6 regulated microRNAs (miRs), miR-23b, in human cervical carcinoma SiHa cells. Thus, the importance of DNA methylation and miR-23b in HPV-16 E6 associated cervical cancer development is investigated.

Clitocine reversal of P-glycoprotein associated multi-drug resistance through down-regulation of transcription factor NF-κB in R-HepG2 cell line.

Multidrug resistance (MDR) is one of the major reasons for failure in cancer chemotherapy and its suppression may increase the efficacy of therapy. The human multidrug resistance 1 (MDR1) gene encodes the plasma membrane P-glycoprotein (P-gp) that pumps various anti-cancer agents out of the cancer cell. R-HepG2 and MES-SA/Dx5 cells are doxorubicin induced P-gp over-expressed MDR sublines of human hepatocellular carcinoma HepG2 cells and human uterine carcinoma MES-SA cells respectively.

Synthesis and antiproliferative activities of novel 5'-Schiff-base group substituted psoralen derivatives.

It was found that psoralen derivative could perform a Friedel-Crafts acylation smoothly with acetic anhydride to give 5'-acetylpsoralen in a 73% yield. In the presence of boron trifluoride etherate, 5'-acetylpsoralen reacted with both aromatic amines and aliphatic amine smoothly to afford 5'-Schiff-base group substituted psoralen derivatives in 72%-92% yields. The novel synthetic method has the advantages of cheap materials, mild reaction conditions, good yields and high regioselectivity in the Friedel-Crafts acylation.

3,5-Dimethyl-H-furo[3,2-g]chromen-7-one as a potential anticancer drug by inducing p53-dependent apoptosis in human hepatoma HepG2 cells.

Background/aims: Coumarins are natural compounds found in many plants that possess medical value by itself and its modified derivatives.

Method: Six novel coumarin derivatives were synthesized and examined for their potential anticancer cytotoxicity.

Result: Among the 6 derivatives, 3,5-dimethyl-(7)H-furo[3,2-g]chromen-7-one (DMFC) presented the strongest cytotoxicity against human hepatoma HepG2 cells in vitro with an IC(50) value of 8.

P-glycoprotein enhances radiation-induced apoptotic cell death through the regulation of miR-16 and Bcl-2 expressions in hepatocellular carcinoma cells.

P-glycoprotein (Pgp), an efflux pump, was confirmed the first time to regulate the expressions of miR/gene in cells. Pgp is known to be associated with multidrug resistance. RHepG2 cells, the multidrug resistant subline of human hepatocellular carcinoma HepG2 cells, expressed higher levels of Pgp as well as miR-16, and lower level of Bcl-2 than the parental cells.

HPV-16 E6 upregulation of DNMT1 through repression of tumor suppressor p53.

The HPV-16 early proteins E6 and E7 are considered to function as oncoproteins in cervical cancer. DNA methyltransferase 1 (DNMT1) is one of the enzymes involved in epigenetic silencing of tumor suppressor genes. In the present study, the functional role and regulation of DNMT1 in HPV-16 E6 associated cervical cancer development were examined.

AF1q enhancement of gamma irradiation-induced apoptosis by up-regulation of BAD expression via NF-kappaB in human squamous carcinoma A431 cells.

BAD (BCL-2 antagonist of cell death) is a pro-apoptotic BCL-2 family protein that plays a critical role in the regulation of apoptotic response. This study presents direct evidence that AF1q increased the radiation-induced apoptosis through up-regulation of BAD in human squamous carcinoma A431 cells and the key transcription factor involved is NF-kappaB. The minimal promoter sequence of BAD was identified; the activity was increased in AF1q stable transfectants and decreased upon AF1q siRNA transfection.

Oncofetal H19-derived miR-675 regulates tumor suppressor RB in human colorectal cancer.

H19 is an imprinted oncofetal non-coding RNA recently shown to be the precursor of miR-675. The pathophysiological roles of H19 and its mature product miR-675 to carcinogenesis have, however, not been defined. By quantitative reverse transcription-polymerase chain reaction, both H19 and miR-675 were found to be upregulated in human colon cancer cell lines and primary human colorectal cancer (CRC) tissues compared with adjacent non-cancerous tissues.

Facilitation of drug resistance development by gamma-irradiation in human cancer cells.

Hepatocellular carcinoma HepG2 cells (G cells) were subjected to selection first with gamma-radiation and then doxorubicin (Dox). The radiation treatment consisted of 2 Gy for 10 days (G2) or 10 Gy for 2 days (G10) and the Dox treatment was continuous exposure for up to 10 microM. Compared with respective parental G, G2, G10 cells, the Dox-selected cells showed mdr1 amplification/P-glycoprotein overexpression, Dox resistance and also less intracellular Dox accumulation.

Mechanistic study on growth suppression and apoptosis induction by targeting hepatoma-derived growth factor in human hepatocellular carcinoma HepG2 cells.

Hepatoma-derived growth factor (HDGF) is frequently overexpressed in human cancer. The growth factor was previously demonstrated to be a survival factor as knock-down of HDGF suppresses the growth and induces apoptosis in human cancer cells through the Bad-mediated intrinsic apoptotic pathway. However, inactivation of Bad cannot completely repress the apoptosis induced upon HDGF knock-down, indicating the presence of other unidentified pathways.

Suillin from the mushroom Suillus placidus as potent apoptosis inducer in human hepatoma HepG2 cells.

During the search of new anti-cancer agent from high fungi, the ethyl acetate extract of the mushroom Suillus placidus was found to exhibit a significant cytotoxic activity against human hepatoma HepG2 cells. With bioassay-guided fractionation, a cytotoxic component suillin was isolated from the extract. The anti-cancer effect of suillin was subsequently examined in 8 human cancer cell lines by using MTT assay.

Estrogen-related receptor alpha (ERRalpha) inverse agonist XCT-790 induces cell death in chemotherapeutic resistant cancer cells.

Estrogen-related receptor alpha (ERRalpha) is primarily thought to regulate energy homeostasis through interacting with peroxisome proliferator-activated receptor gamma coactivator-1alpha and -1beta (PGC-1alpha and -1beta). They coordinately control the transcription of genes in the oxidative phosphorylation pathway. In addition to its role in energy metabolism, ERRalpha has also been implicated as a prognostic marker for breast, ovarian, colon and prostate cancers.

The miR-18a* microRNA functions as a potential tumor suppressor by targeting on K-Ras.

The Ras proto-oncogene mediates a wide variety of cellular events and is frequently mutated in cancer. MicroRNAs (miRNAs) may regulate the development of cancer through their effect on the target genes. In the search of miRNAs that target on Ras, miR-18a* is the first time confirmed to target on K-Ras and furthermore not on N- and H-Ras.

Epigallocatechin gallate up-regulation of miR-16 and induction of apoptosis in human cancer cells.

Epigallocatechin gallate (EGCG) is a major type of green tea polyphenols and is known to have cancer prevention effect. MicroRNAs (miRNAs) are 19 to 25 nucleotides and are believed to be important in gene regulation. In the present study, the influence of EGCG on the expressions of miRNAs in human cancer cells was investigated as this has not yet been reported.

Oncogene AF1q enhances doxorubicin-induced apoptosis through BAD-mediated mitochondrial apoptotic pathway.

AF1q is an oncogenic factor involved in leukemia development, thyroid tumorigenesis, and breast cancer metastasis. In the present study, AF1q was found to be down-regulated in a doxorubicin-resistant subline of human squamous carcinoma A431 cells. Knockdown of AF1q decreased the apoptosis induced by doxorubicin, Taxol, gamma-radiation, IFN-alpha, and IFN-gamma in A431 cells.

Let-7a microRNA suppresses therapeutics-induced cancer cell death by targeting caspase-3.

MicroRNAs (miRNA) are endogenously expressed non-coding RNAs that regulate gene expression post-transcriptionally. Let-7a miRNA is a founding member in the let-7 family and its down-regulation in association with over-expression of RAS and HMGA2 oncogenes has previously been reported. In the present study, caspase-3, the executioner caspase, was confirmed to be the target of let-7a as ectopic expression of let-7a decreased the luciferase activity of a reporter construct containing the 3' untranslated region of caspase-3 and at the same time repressed the enzyme expression in human squamous carcinoma A431 cells and hepatocellular carcinoma HepG2 cells.

Downregulation of hepatoma-derived growth factor activates the Bad-mediated apoptotic pathway in human cancer cells.

Hepatoma-derived growth factor (HDGF) is highly expressed in human cancer and its expression is correlated with poor prognosis of cancer. The growth factor is known to stimulate cell growth while the underlying mechanism is however not clear. Transfection with HDGF cDNA stimulated while its specific antisense oligonucleotides repressed the growth of human hepatocellular carcinoma HepG2 cells.

Induction of drug resistance and transformation in human cancer cells by the noncoding RNA CUDR.

Refractory to apoptosis induced by anticancer drugs is one of the major causes of drug resistance in human cancers. The involvement of noncoding RNA (ncRNA) in cancer cell drug resistance has not yet been reported. By using the technique of RT-PCR-based differential display, a novel gene, cancer up-regulated drug resistant (CUDR) gene, was found to be overexpressed in a doxorubicin-resistant subline of human squamous carcinoma A431 and A10A cells, which were also more resistant to drug-induced apoptosis.

p53-R273H gains new function in induction of drug resistance through down-regulation of procaspase-3.

Development of drug resistance is one of the major obstacles in cancer chemotherapy. The molecular mechanism leading to drug resistance is still not fully understood. A10A cells, a doxorubicin-resistant subline of human squamous cell carcinoma A431 cells, showed cross-resistance to methotrexate and also resistance to the drug-induced apoptosis.

Cell polarity protein Par3 complexes with DNA-PK via Ku70 and regulates DNA double-strand break repair.

The partitioning-defective 3 (Par3), a key component in the conserved Par3/Par6/aPKC complex, plays fundamental roles in cell polarity. Herein we report the identification of Ku70 and Ku80 as novel Par3-interacting proteins through an in vitro binding assay followed by liquid chromatography-tandem mass spectrometry. Ku70/Ku80 proteins are two key regulatory subunits of the DNA-dependent protein kinase (DNA-PK), which plays an essential role in repairing double-strand DNA breaks (DSBs).

Epidermal growth factor induction of resistance to topoisomerase II toxins in human squamous carcinoma A431 cells.

Alteration of the epidermal growth factor (EGF) signaling pathway occurs frequently in human cancer cells and may subsequently affect the cell survival towards anti-cancer agents. To elucidate the effect of long-term EGF treatment on the chemo-sensitivity of human cancer cells, human squamous carcinoma A431 cells (AP) were incubated continuously with 50 ng/ml EGF for 30 weeks and these cells were designated as the AC cells. The long-term EGF treatment did not alter the EGFR level and the EGF-induced protein tyrosine phosphorylation pattern in the AC cells.

p53-R175H mutant gains new function in regulation of doxorubicin-induced apoptosis.

Mutation of tumor suppressor p53 gene gains new function in regulation of DNA damage-induced apoptotic response in tumor cells, which may lead to a poor response in cancer chemotherapy and radiotherapy. Transfection of mutant p53 (R175H) to p53-null osteosarcoma Saos-2 cells suppressed apoptosis induced by doxorubicin (DOX), cisplatin and gamma radiation. Downregulation of caspase-3 but not -8 or -9 basal protein levels was also observed in Saos-2 cells transfected with p53-R175H.

Modulation of multidrug resistance-associated protein 1 (MRP1) by p53 mutant in Saos-2 cells.

The p53 tumor suppressor gene is one of the most frequently mutated genes in human cancer and the mutation is correlated with a poor prognosis in cancer therapy. Upregulation of multidrug resistance-associated protein 1 (MRP1) and increase in drug resistance have been found to be induced by p53 mutation. Human osteosarcoma Saos-2 cells, a p53-null cell line, was transfected with p53 with mutations at codon 143 (V to A), 175 (R to H), 248 (R to W), 273 (R to H) and 281 (D to G).