• Asian Pacific Journal of Cancer Prevention
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• v.14 no.4
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• pp.2495-2502
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• 2013

Background: Dietary fat has been inconsistently associated with the risk of breast cancer. The purpose of this study was to examine the relationship between meat and animal and plant fat intake and breast cancer risk in subgroups by total lifetime physical activity, using data from a case-control study conducted in the Region of Western Pomerania, Poland. Materials and Methods: The study included 858 women with histological confirmed breast cancer and 1,085 controls, free of any cancer diagnosis. The study was based on a self-administered questionnaire including questions about socio-demographic characteristics, current weight and height, reproductive factors, family history of breast cancer and lifestyle habits. Unconditional logistic regression was performed to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Results: High animal fat intake significantly increased OR from 1.7 times (OR=1.66, 95%CI=1.07-3.59) to 2.9 times (OR=2.9, 95%CI=1.37-6.14) independent of physical activity level, comparing the third versus the lowest quartile. Women with a high intake of red meat or processed meat and low physical activity showed increased risk of breast cancer: OR=2.70, 95%CI=1.21-6.03 and 1.78, 95%CI=1.04-3.59, respectively. The plant fat dietary pattern was negatively associated with breast cancer in sedentary women (OR=0.57, 95%CI=0.32-0.99). Conclusions: These results indicated that a diet characterized by a high consumption of animal fat is associated with a higher breast cancer risk in sedentary women, while consumption of plant fat products may reduce risk in the same group.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.11
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• pp.4601-4607
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• 2014

Red rice contains pharmacological substances including phenolics, oryzanol, tocotrienol and tocopherol. Recently, red rice extract has been employed as a source of antioxidants for inhibition of tumor growth. This study was carried out to evaluate the anti-invasion effects of red rice extract fractions on cancer cells. It was found that at $100{\mu}g/ml$ of crude ethanolic extract (CEE), hexane fraction (Hex) and dichloromethane fraction (DCM) could reduce HT1080 and MDA-MB-231 cancer cell invasion. Hex and DCM revealed higher potency levels than CEE, whereas an ethyl acetate fraction (EtOAc) had no effect. Gelatin zymography revealed that Hex decreased the secretion and activity of matrix metalloproteinase-2 and -9 (MMP-2 and-9). In contrast, the DCM fraction exhibited slightly effect on MMPs secretion and had no effect on MMPs activity. Collagenase activity was significantly inhibited by the Hex and DCM fractions. High amounts of ${\gamma}$-oryzanol and ${\gamma}$-tocotrienol were found in the Hex and DCM fractions and demonstrated an anti-invasion property. On the other hand, proanthocyanidin was detected only in the CEE fraction and reduced MDA-MB-231 cells invasion property. These observations suggest that proanthocyanidin, ${\gamma}$-oryzanol and ${\gamma}$-tocotrienol in the red rice fractions might be responsible for the anti invasion activity. The red rice extract may have a potential to serve as a food-derived chemotherapeutic agent for cancer patients.

• Biomolecules & Therapeutics
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• v.15 no.1
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• pp.27-33
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• 2007

The psychopharmacological profile of ginsenosides has not yet been confirmed systematically although various neuropharmacological activities associated with them have been investigated. In the present study, the psychological activities of Rb1 were investigated to evaluate whether it can be used in treatment or prevention of psychological disorders. Rb1 was intravenously injected at doses of O.2,2,5 and 10 mg/kg. The effects of Rb1 on the $Cl^-$ ion influx were investigated using IMR-32 human neuroblastoma cells. Moreover, locomotor activity, forced swimming activity, activity on rotating rod and activity in elevated plus-maze were tested in mice. Rb1 increased the $Cl^-$ influx into the intracell region in a dose-dependent manner. Rb1 did not cause change in behavior in total open field when locomotor activity was tested, however it increased activities, especially, such as rearing frequency in center area. Administration of Rb1 at 0.2 mg/kg significantly reduced activities on rotating rod however administration at high dosages had no effect on them. Rb1 administration decreased animal immobile time in a water chamber in a dose dependent manner, and increased the strong mobile time of animals. In conclusion, the present results demonstrate that Rb1 contributes to the psychopharmacological effects of ginseng and may be used in treatment or prevention of psychological disorders such as anxiety or depression.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.16
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• pp.6911-6917
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• 2014

Background: Hepatocellular carcinoma is a complex and heterogeneous tumor with poor prognosis due to frequent intrahepatic spread and extrahepatic metastasis. The molecular mechanisms underlying HCC pathogenesis still remain obscure. Objectives: We aimed to investigate the abundance and the DNA binding activity of nuclear factor kappa B/p65 subunit in peripheral blood mononuclear cells from patients with HCC and to assess its prognostic significance and association with hypoxia inducible factor one alpha (HIF-$1{\alpha}$) in blood. Subjects and methods: This study was carried out on 40 patients classified equally into liver cirrhosis (group I) and HCC (group II), in addition to 20 healthy volunteers (group III). All groups were subjected to measurement of NF-${\kappa}B$/P65 subunit expression levels by real time-PCR, and DNA binding activity was evaluated by transcription factor binding immunoassay. Serum HIF-$1{\alpha}$ levels were estimated by enzyme-linked immunosorbent assay (ELISA). Significant increase of both the expression level and DNA binding activity of NF-${\kappa}B$/P65 subunit together with serum HIF-1 alpha levels was noted in HCC patients compared to liver cirrhosis and control subjects, with significant positive correlation with parameters for bad prognosis of HCC. In conclusion, NF-${\kappa}B$ signaling is activated in HCC and associated with disease prognosis and with high circulating levels of HIF-1 alpha.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.3
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• pp.1299-1306
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• 2014

Background: Nano-biotechnology is recognized as offering revolutionary changes in various fields of medicine. Biologically synthesized silver nanoparticles have a wide range of applications. Materials and Methods: Silver nanoparticles (AgNPs) were biosynthesized with an aqueous extract of Pterocladiella (Pterocladia) capillacea, used as a reducing and stabilizing agent, and characterized using UV-VIS spectroscopy, Fourier Transform Infra red (FT-IR) spectroscopy, transmission electron microscopy (TEM) and energy dispersive analysis (EDX). The biosynthesized AgNPs were tested for cytotoxic activity in a human hepatocellular carcinoma ($HepG_2$) cell line cultured in Dulbecco's modified Eagle medium supplemented with 10% fetal bovine serum, 1% antibiotic and antimycotic solution and 2 mM glutamine. Bacterial susceptibility to AgNPs was assessed with Staphylococcus aureus, Bacillus subtilis [Gram+ve] and Pseudomonas aeruginosa and Escherichia coli [Gram-ve]. The agar well diffusion technique was adopted to evaluate the bactericidal activity of the biosynthesized AgNPs using Ampicillin and Gentamicin as gram+ve and gram-ve antibacterial standard drugs, respectively. Results: The biosynthesized AgNPs were $11.4{\pm}3.52$ nm in diameter. FT-IR analysis showed that carbonyl groups from the amino acid residues and proteins could assist in formation and stabilization of AgNPs. The AgNPs showed potent cytotoxic activity against the human hepatocellular carcinoma ($HepG_2$) cell line at higher concentrations. The results also showed that the biosynthesized AgNPs inhibited the entire panel of tested bacteria with a marked specificity towards Bacillus subtillus. Conclusions: Cytotoxic activity of the biosynthesized AgNPs may be due to the presence of alkaloids present in the algal extract. Our AgNPs appear more bactericidal against gram-positive bacteria (B. subtillus).

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.12
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• pp.4919-4923
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• 2014

Background: To investigate the effect of celecoxib on telomerase activity and apoptosis in a human laryngeal squamous carcinoma cell line (Hep-2 cells). Materials and Methods: The growth inhibition rate of Hep-2 cells in vitro was measured by MTT assay, and apoptosis by TUNEL assay and flow cytometry (FCM). The TRAP-ELISA method was used to determine telomerase activity in Hep-2 cells. The mRNA expression of human telomerase RNA component(hTR), human telomerase reverse transcriptase (hTERT) and human telomerase-associated protein(hTEP1) was determined by RT-PCR assay. Expression of Bax and Bcl-2 proteins was assessed by Western blotting. Results: Celecoxib can inhibit proliferation and induce apoptosis in a dose- and time-dependent manner, repress telomerase activity, decrease hTERT mRNA and Bcl-2 protein expression and increase Bax protein expression, PGE2 had no effect on telomerase. Conclusions: Celecoxib had the antiproliferative and pro-apoptotic effect in Hep-2 cells. Apoptosis was accompanied by a decrease in telomerase activity which was directly correlated with hTERT mRNA and up-regulation of Bax/Bcl-2. Bcl-2 may thus play an important role in telomerase activity as well as apoptosis.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.18
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• pp.8177-8186
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• 2016

The present study was aimed at determining the effects of alkylating and oxidative stress inducing agents on a newly identified variant of DNA polymerase beta ($pol{\beta}{\Delta}_{208-304}$) specific for ovarian cancer. $Pol{\beta}{\Delta}_{208-304}$ has a deletion of exons 11-13 which lie in the catalytic part of enzyme. We compared the effect of these chemicals on HeLa cells and HeLa cells stably transfected with this variant cloned into in pcDNAI/neo vector by MTT, colony forming and apoptosis assays. $Pol{\beta}{\Delta}_{208-304}$ cells exhibited greater sensitivity to an alkylating agent and less sensitivity towards $H_2O_2$ and UV when compared with HeLa cells alone. It has been shown that cell death in $Pol{\beta}{\Delta}_{208-304}$ transfected HeLa cells is mediated by the caspase 9 cascade. Exon 11 has nucleotidyl selection activity, while exons 12 and 13 have dNTP selection activity. Hence deletion of this part may affect polymerizing activity although single strand binding and double strand binding activity may remain same. The lack of this part may adversely affect catalytic activity of DNA polymerase beta so that the variant may act as a dominant negative mutant. This would represent clinical significance if translated into a clinical setting because resistance to radiation or chemotherapy during the relapse of the disease could be potentially overcome by this approach.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.13
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• pp.5421-5425
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• 2015

To evaluate the relationship between the growth hormone 1 (GH1) T1663A polymorphism, recreational physical activity and body mass index (BMI) with reference to breast cancer, we conducted a case-control study with 669 cases of breast cancer and 682 population-based controls in Jiangsu Province, China. A structured questionnaire was used to elicit detailed information. All subjects completed an in-person interview. GH1 genotypes were identified using PCR-RFLP methods. Odds ratios (ORs) were estimated with an unconditional logistic model. The distribution of GH1 genotypes was not significantly different between controls and cases ($x^2$=2.576, P=0.276). Results of stratified analysis by the participation status of the recreational physical activity showed that the persons with GH1 A allele were at a decreased risk of breast cancer (adjusted-OR=0.66; 95% CI, 0.50-0.87) only among inactive individuals. Stratified analysis by BMI showed that the genotype A/A was associated with a decreased risk of breast cancer only among individuals of the BMI <25 (adjusted-OR=0.80; 95% CI, 0.66-0.98). The findings of this study suggest that recreational physical activity and BMI may modify any association between the GH1 T1663A polymorphism and breast cancer risk.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.2
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• pp.617-622
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• 2014

Voacanga globosa (Blanco), a plant endemic to the Philippines, is traditionally used especially by indigenous people of Bataan in the treatment of ulcers, wounds and tumorous growths. This study aimed to provide scientific evidence to therapeutic properties by determining cytotoxic and pro-apoptotic activity of HPLC fractions from leaves on HCT116 human colon carcinoma and A549 human lung carcinoma cell lines. Ethanolic extraction was performed on V globosa leaves followed by hexane and ethyl acetate partitioning. Silica gel column chromatography and high performance liquid chromatography (HPLC) produced MP1, MP2 and MP3 fractions. Cytotoxic activity of the fractions was determined through MTT assay against the cancer cell lines HCT116 and A549 and the non-cancer AA8 Chinese hamster ovarian cell line. Pro-apoptotic activities of the most active fractions were further assessed through DAPI staining, TUNEL assay and JC-1 mitochondrial membrane potential assay with HCT116 cells. While the MPI fraction exerted no significant activity against all cell lines tested, MP2 and MP3 fractions demonstrated high toxicity against HCT116 and A549 cells. The MP3 fraction induced formation of apoptotic bodies, condensed DNA and other morphological changes consistent with apoptosis of HCT116 cells and TUNEL assay showed significant increase in DNA fragmentation over time. In these cells, the MP3 fraction also induced mitochondrial membrane destabilization, which is generally associated with the beginning of apoptosis. Phytochemical analysis demonstrated the presence only of saponins and terpenoids in the MP3 fraction. The results indicate that the MP3 fraction exerts cytotoxic activity on HCT116 cells via induction of apoptosis triggered by loss of mitochondrial membrane potential crucial for cell survival.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.7
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• pp.3559-3567
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• 2016

Background: In recent years, there has been considerable research on recycling of agro-industrial waste for production of bioactive compounds. The food processing industry produces large amounts of citrus peels that may be an inexpensive source of useful agents. Objective: The present work aimed to explore the phytochemical content, antioxidant, anticancer, antiproliferation, and antigenotxic activities of lemon, grapefruit, and mandarin peels. Materials and Methods: Peels were extracted using 98% ethanol and the three crude extracts were assessed for their total polyphenol content (TPC), total flavonoid content (TFC), and antioxidant activity using DPPH (1, 1-diphenyl-2-picrylhydrazyl). Their cytotoxic and mitogenic proliferation activities were also studied in human leukemia HL-60 cells and mouse splenocytes by CCK-8 assay. In addition, genotoxic/antigenotoxic activity was explored in mouse splenocytes using chromosomal aberrations (CAs) assay. Results: Lemon peels had the highest of TPC followed by grapefruit and mandarin. In contrast, mandarin peels contained the highest of TFC followed by lemon and grapefruit peels. Among the extracts, lemon peel possessed the strongest antioxidant activity as indicated by the highest DPPH radical scavenging, the lowest effective concentration 50% ($EC_{50}=42.97{\mu}g\;extract/mL$), and the highest Trolox equivalent antioxidant capacity (TEAC=0.157). Mandarin peel exhibited moderate cytotoxic activity ($IC_{50}=77.8{\mu}g/mL$) against HL-60 cells, whereas grapefruit and lemon peels were ineffective anti-leukemia. Further, citrus peels possessed immunostimulation activity via augmentation of proliferation of mouse splenocytes (T-lymphocytes). Citrus extracts exerted non-cytotoxic, and antigenotoxic activities through remarkable reduction of CAs induced by cisplatin in mouse splenocytes for 24 h. Conclusions: The phytochemical constituents of the citrus peels may exert biological activities including anticancer, immunostimulation and antigenotoxic potential.