• Asian Pacific Journal of Cancer Prevention
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• v.13 no.7
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• pp.3471-3476
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• 2012

Background and Objective: Histone deacetylase (HDAC) inhibitors represent a promising class of potential anticancer agents for treatment of human malignancies. In this study, we investigated the effect of trichostatin A (TSA), one such HDAC inhibitor, in combination with docetaxel (TXT), a cytotoxic chemotherapy agent or erlotinib, a novel molecular target therapy drug, on lung cancer A549 cells. Methods: A549 cells were treated with TXT, erlotinib alone or in combination with TSA, respectively. Cell viability, apoptosis, and cell cycle distribution were evaluated using MTT (3- (4, 5-dimethylthiazol-2-yl) -2, 5-diphenyltetrazolium bromide) assay, Hochst33258 staining and flow cytometry. Moreover, immunofluorescent staining and Western blot analysis were employed to examine alterations of ${\alpha}$-tubulin, heat shock protein 90 (hsp90), epidermal growth factor receptor (EGFR), and caspase-3 in response to the different exogenous stimuli. Results: Compared with single-agent treatment, co-treatment of A549 cells with TSA/TXT or TSA/erlotinib synergistically inhibited cell proliferation, induced apoptosis, and caused cell cycle delay at the $G_2/M$ transition. Treatment with TSA/TXT or TSA/erlotinib led to a significant increase of cleaved caspase-3 expression, also resulting in elevated acetylation of ${\alpha}$-tubulin or hsp90 and decreased expression of EGFR, which was negatively associated with the level of acetylated hsp90. Conclusions: Synergistic anti-tumor effects are observed between TXT or erlotinib and TSA on lung cancer cells. Such combinations may provide a more effective strategy for treating human lung cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.10
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• pp.5663-5669
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• 2013

The histone methyltransferase EZH2 (enhancer of zeste homolog 2) plays critical roles in prostate cancer (PCa) development and is a potential target for PCa treatment. Triptolide possesses anti-tumor activity, but it is unknown whether its therapeutic effect relates with EZH2 in PCa. Here we described EZH2 as a target for Triptolide in PCa cells. Our data showed that Triptolide suppressed PCa cell growth and reduced the expression of EZH2. Overexpression of EZH2 attenuated the Triptolide induced cell growth inhibition. Moreover, Triptolide treatment of PC-3 cells resulted in elevated mRNA levels of target genes (ADRB2, CDH1, CDKN2A and DAB2IP) negatively regulated by EZH2 as well as reduced mRNA levelsan of EZH2 positively regulated gene (cyclin D1). Our findings suggest the PCa cell growth inhibition mediated by Triptolide might be associated with downregulation of EZH2 expression and the subsequent modulation of target genes.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.10
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• pp.5849-5854
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• 2013

Background: Apoptosis may be induced after Bcl-2 expression is inhibited in proliferative cancer cells. This study focused on the effect of autophagy activation by ABT737 on anti-tumor effects of epirubicin. Methods: Cytotoxic effects of ABT737 on the HepG2 liver cancer cell line were assessed by MTT assay and cell apoptosis through flow cytometry. Mitochondrial membrane potential was measured by fluorescence microscopy. Monodansylcadaverin (MDC) staining was used to detect activation of autophagy. Expression of p53, p62, LC3, and Beclin1, apoptotic or autophagy related proteins, was detected by Western blotting. Results: ABT737 and epirubicin induced growth inhibition in HepG2 cells in a dose- and time-dependent manner. Both ABT737 and epirubicin alone could induce cell apoptosis with a reduction in mitochondrial membrane potential as well as increased apoptotic protein expression. Further increase of apoptosis was detected when HepG2 cells were co-treated with ABT373 and epirubicin. Furthermore, our results demonstrated that ABT373 or epirubicin ccould activate cell autophagy with elevated autophagosome formation, increased expression of autophagy related proteins and LC3 fluorescent puncta. Conclusions: ABT737 influences cancer cells through both apoptotic and autophagic mechanisms, and ABT737 may enhance the effects of epirubicin on HepG2 cells by activating autophagy and inducing apoptosis.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.10
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• pp.5783-5788
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• 2013

Trigonella foenum in graecum (Fenugreek) is a traditional herbal plant used to treat disorders like diabetes, high cholesterol, wounds, inflammation, gastrointestinal ailments, and it is believed to have anti-tumor properties, although the mechanisms for the activity remain to be elucidated. In this study, we prepared a methanol extract from Fenugreek whole plants and investigated the mechanism involved in its growth-inhibitory effect on MCF-7 human breast cancer cells. Apoptosis of MCF-7 cells was evidenced by investigating trypan blue exclusion, TUNEL and Caspase 3, 8, 9, p53, FADD, Bax and Bak by real-time PCR assays inducing activities, in the presence of FME at $65{\mu}g/mL$ for 24 and 48 hours. FME induced apoptosis was mediated by the death receptor pathway as demonstrated by the increased level of Fas receptor expression after FME treatment. However, such change was found to be absent in Caspase 3, 8, 9, p53, FADD, Bax and Bak, which was confirmed by a time-dependent and dose-dependent manner. In summary, these data demonstrate that at least 90% of FME induced apoptosis in breast cell is mediated by Fas receptor-independently of either FADD, Caspase 8 or 3, as well as p53 interdependently.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.10
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• pp.4169-4172
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• 2015

Background: Oral carcinoma (OC) remains as one of the most difficult malignancies to cure. Hesa-A is an Iranian herbal-marine compound that has shown promising anti-tumor properties on various human cancer cells, although the mechanisms of action remain to be addressed. This study was conducted to evaluate the effect of two doses of Hesa-A on mRNA expression of p53 as a main prognosticator of OC. Materials and Methods: 60 rats were randomly divided into 5 groups of 12 animals each. Rats in carcinoma groups received 0, 250 and 500 mg/kg body weight of Hesa-A three times a day. The two other groups considered as treated and untreated healthy groups. At the end of experiment, animals were sacrificed and tongue tissues subjected to H and E staining and real time PCR. Results: Our results indicated that compared to healthy group, p53 over expressed ~ 40% in untreated carcinoma group. After treatment with 250mg/kg and 500mg/kg body weights of Hesa-A, p53 level dropped by 53.4% and 13.6 %, respectively, compared to untreated carcinoma group (p<0.05, p<0.0001). Moreover, there was a significant relation between p53 mRNA content and observed pathological changes in studied groups (p<0.05). Conclusions: These data provide insights into the mechanism(s) by which Hesa-A improves clinical outcome of oral carcinoma by modulation of p53 expression.

• Herbal Formula Science
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• v.11 no.1
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• pp.115-128
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• 2003

Bojungikgitang is the water extracts prepared from Ginseng Radix, Astragali Radix, Angelicae gigantis Radix, Astractylodis Rhizoma alba, Aurantii nobilis Pericarpium, Glycyrrhizae Radix, Bupleuri Radix, Cimicifugae Rhizoma, which has been used for the treatment of indigestion, and immunological disease in oriental countries. In this study, the effects of Bojungikgitang on the productions of nitiric oxide (NO) and prostaglandin $E_2\;(PGE_2)$, and the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were examined using RAW 264.7 macrophages activated with $interferon-{\gamma}\;(IFN-{\gamma})$ plus lipopolysaccharide (LPS). Bojungikgitang (10-400 ${\mu}$g/ml) per se had no cytotoxic effect in unstimulated macrophages, but this compound dose-dependently reduced the release of NO and $PGE_2$ caused by stimulation of $LPS/IFN-{\gamma}$. The levels of iNOS and COX-2 protein were markedly suppressed by the treatment with Bojungikgitang in a concentration dependent manner. Moreover, Bojungikgitang also attenuated the production of tumor necrosis factor (TNF)-${\alpha}$, interleukin (1L)-1${\beta}$ and IL-6 in LPS-stimulated RAW 264.7 macrophages. These results suggest that Bojungikgitang decreases the NO and $PGE_2$ production in macrophages by inhibiting iNOS and COX-2 expression and these properties may contribute to the anti-inflammatory activity of Bojungikgitang.

• Journal of Acupuncture Research
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• v.32 no.3
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• pp.15-25
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• 2015

Objectives : The purpose of this study is to investigate the effects of Pyrrosiae Herba herbal-acupuncture(PH-HA) at $KI_{10}$(Umgok) on nephritis induced by lipopolysaccharide(LPS) in rats. Methods : Rats were assigned to four groups: normal, LPS, saline and PH-HA. Rats in the saline and PH-HA groups were treated with saline injection and PH-HA respectively at $KI_{10}$, three times over the period of one week. All animals, except those in the normal group, were injected intra-peritoneally with LPS to induce nephritis. WBC, in blood, tumor necrosis factor alpha(TNF-${\alpha}$), cytokine-induced neutrophil chemoattractant 1(CINC-1), blood urea nitrogen(BUN), creatinine in serum, urinal volume, total protein creatinine in urine, and renal myeloperoxidase (MPO) were analyzed. Results : 1. PH-HA group showed significantly reduced levels of serum BUN, serum creatinine, TNF-${\alpha}$, and CINC-1 compared to the LPS group. Furthermore, a significant increase in urine output and more significant decreases in total protein in urine and MPO in renal tissue were observed in the PH-HA group when compared to the LPS group. 2. The PH-HA group showed significantly reduced levels of serum creatinine and renal MPO, and a more significant increase in urine output compared to the saline group. Conclusions : According to these results, it is postulated that PH-HA at $KI_{10}$ has anti-inflammatory and renal-protective effects on LPS-induced nephritis in rats, and both acupoint $KI_{10}$ and the herb Pyrrosiae Herba made contributions to these effects. Further studies on the interaction between acupoint $KI_{10}$ and the herb Pyrrosiae Herba may be needed.

• The Korea Journal of Herbology
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• v.35 no.6
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• pp.55-68
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• 2020

Objectives : We observed the possibilities that blue honeysuckle has favorable analgesic or refinement effects on the Primary dysmenorrhea (PD) in rats. Methods : Estradiol benzoate and oxytocin were used to induce the PD rat model. And Blue honeysuckle concentration lyophilized powders (BH) 500, 250 and 125 mg/kg and 500 mg/kg of Lonicerae Flos aqueous extract lyophilized powders (LF) were orally administered, once a day for 10 days at 30 min after each estradiol benzoate treatment. Then the changes on the body weights and gains during experimental periods, abdominal writhing response for analgesic activities, uterine weights, uterus lipid peroxidation, antioxidant defense system - glutathione contents, superoxide dismutase and catalase activities, NF-κB and COX-2 mRNA expressions were monitored with uterus histopathology including immunohistochemistry for tumor necrosis factor (TNF)-α and inducible nitric oxide synthase (iNOS).. Results : Inflammatory and oxidative stress mediated PD signs were favorably and dose-dependently inhibited by 10 days continuous oral administration of three different dosages of BH - 500, 250 and 125 mg/kg as comparable to those of indomethacin(IND) 5 mg/kg treated rats in BH 500 mg/kg administered PD rats, and similar to those of LF 500 mg/kg in BH 125 mg/kg, at least in a condition of the present PD rat model. Conclusions : The results suggest that BH has favorable analgesic and refinement activities on the estradiol benzoate and oxytocin treatment-induced PD signs through anti-inflammatory and antioxidative potentials.

• Nutrition Research and Practice
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• v.10 no.3
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• pp.259-264
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• 2016

BACKGROUND/OBJECTIVES: Stromal cell-derived growth factor 1 (SDF-1), also known as chemokine ligand 12, and chemokine receptor type 4 are involved in cancer cell migration. Compound K (CK), a metabolite of protopanaxadiol-type ginsenoside by gut microbiota, is reported to have therapeutic potential in cancer therapy. However, the inhibitory effect of CK on SDF-1 pathway-induced migration of glioma has not yet been established. MATERIALS/METHODS: Cytotoxicity of CK in C6 glioma cells was determined using an EZ-Cytox cell viability assay kit. Cell migration was tested using the wound healing and Boyden chamber assay. Phosphorylation levels of protein kinase C $(PKC){\alpha}$ and extracellular signal-regulated kinase (ERK) were measured by western blot assay, and matrix metallopeptidases (MMP) were measured by gelatin-zymography analysis. RESULTS: CK significantly reduced the phosphorylation of $PKC{\alpha}$ and ERK1/2, expression of MMP9 and MMP2, and inhibited the migration of C6 glioma cells under SDF-1-stimulated conditions. CONCLUSIONS: CK is a cell migration inhibitor that inhibits C6 glioma cell migration by regulating its downstream signaling molecules including $PKC{\alpha}$, ERK1/2, and MMPs.

• Journal of the Korean Society of Food Science and Nutrition
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• v.41 no.3
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• pp.310-319
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• 2012

In order to investigate the biological effects of conformational changes in the folding state of bovine ${\alpha}$-lactalbumin (${\alpha}$-La), the protein was prepared and classified as apo form, microbial transglutaminase (MTGase) added form, or bovine ${\alpha}$-La made lethal to tumor cell (BAMLET) form. Apo ${\alpha}$-La form showed weaker cancer cell inhibitory activity (apoptosis) than native ${\alpha}$-La, which suggests that the metal ion-like $Ca^{2+}$ had a positive effect, whereas BAMLET form showed strong cancer cell apoptotic activity. The BAMLET form seemed to be a molten globule structure that increased hydrophobicity. MTGase added to apo ${\alpha}$-La polymer showed similar anti-cancer activity as native ${\alpha}$-La, and it was well hydrolyzed by digestive enzymes. NMR results showed that BAMLET interacted with oleic acid and produced a complex.