• Journal of the Korean Society of Food Science and Nutrition
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• v.45 no.1
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• pp.137-142
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• 2016

We investigated the anti-proliferative effects of solar salt and purified salt (PS) on HepG2 human hepatocellular cancer cells as well as their effects on mRNA and protein expression of apoptosis- and cell cycle-related genes, including Bcl-2, Bax, p53, and p21. Each salt sample suppressed cancer cell proliferation when treated at a concentration of 0.5% or 1%. Especially solar salt from T salt field (SS-T) and solar salt from Y salt field (SS-Y) significantly suppressed proliferation of cancer cells in comparison with PS. Treatment of HepG2 cells with salt samples at a concentration of 1% suppressed expression of Bcl-2 and promoted expression of Bax, p53, and p21 at the mRNA and protein levels in comparison with the control group. Inductively coupled plasma optical emission spectrometry (ICP-OES) showed that SS-T and SS-Y had higher concentrations of Ca, Mg, S, and K than PS, and SS-T contained higher concentrations of these minerals than SS-Y. It seems that Na and mineral contents in solar salt may contribute to regulation of the genes. Taken together, salt, especially mineral rich solar salt, inhibits cancer cell growth by regulating apoptosis and cell cycle-related genes.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.8
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• pp.3731-3736
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• 2014

Phytic acid (PA) has been reported to have positive nutritional benefits and prevent cancer formation. This study investigated the anticancer activity of rice bran PA against hepatocellular carcinoma (HepG2) cells. Cytotoxicty of PA (0.5 to 4mM) was examined by MTT and LDH assays after 24 and 48h treatment. Apoptotic activity was evaluated by expression analysis of apoptosis-regulatory genes [i.e. p53, Bcl-2, Bax, Caspase-3 and -9] by reverse transcriptase-PCR and DNA fragmentation assay. The results showed antioxidant activity of PA in Fe3+ reducing power assay ($p{\leq}0.03$). PA inhibited the growth of HepG2 cells in a concentration dependent manner ($p{\leq}0.04$). After 48h treatment, cell viability was recorded 84.7, 74.4, 65.6, 49.6, 36.0 and 23.8% in MTT assay and 92.6, 77.0%, 66.8%, 51.2, 40.3 and 32.3% in LDH assay at concentrations of 1, 1.5, 2.0, 2.5, 3.0, and 3.5mM, respectively. Hence, treatment of PA for 24h, recorded viability of cells 93.5, 88.6, 55.5, 34.6 and 24.4% in MTT assay and 94.2, 86.1%, 59.7%, 42.3 and 31.6%, in LDH assay at concentrations of 1, 2.2, 3.0, 3.6 and 4.0mM, respectively. PA treated HepG2 cells showed up-regulation of p53, Bax, Caspase-3 and -9, and down-regulation of Bcl-2 gene ($p{\leq}0.01$). At the $IC_{50}$ (2.49mM) of PA, the p53, Bax, Caspase-3 and-9 genes were up-regulated by 6.03, 7.37, 19.7 and 14.5 fold respectively. Also, the fragmented genomic DNA in PA treated cells provided evidence of apoptosis. Our study confirmed the biological activity of PA and demonstrated growth inhibition and induction of apoptosis in HepG2 cells with modulation of the expression of apoptosis-regulatory genes.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.4
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• pp.1817-1821
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• 2016

Objectives: To observed the effects of ginsenoside -Rh2 (GS-Rh2) on proliferation and apoptosis of side population (SP) human gastric cancer SGC-7901 cells. Materials and Methods: SGC-7901 SP and Non-SP cells were sorted by flow cytometry and assessed using the cck-8 method. Expression of apoptosis-related proteins Bax and Bcl-2 of SP before and after the intervention was determined by Western-blotting. Results: It was found that the proliferation of SP was significantly faster than that of NSP (P<0.05). In addition, GS-Rh2 inhibited proliferation of gastric cancer SP cells, induced cell cycle arrest and cell apoptosis, and changed the expression of BAX/Bcl-2 proteins in a time-dependent and concentration-dependent manner (P<0.05). Conclusions: With increase of GS-Rh2 dose, GS-Rh2 gradually inhibit the proliferation of SGC-7901 SP cells, which have high proliferation rate, through G1/G0 phase arrest, followed by apoptosis which involves the up-regulation of Bax and the down-regulation of Bcl-2.

• Natural Product Sciences
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• v.20 no.4
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• pp.262-268
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• 2014

Rutaecarpine is one of the major alkaloids present in the fruits of Evodia rutaecarpa. In this study, rutaecarpine was evaluated, both in vitro and in vivo, for its hepatoprotective properties against thioacetamide (TAA)-induced hepatic fibrosis. The results showed that rutaecarpine inhibited TAA-induced cytotoxicity, reduced the expression of the fibrogenic cytokine transforming growth factor ${\beta}1$ ($TGF-{\beta}1$), and induced the expression of bcl-2. To evaluate its in vivo effects, animal models with TAA-induced hepatic fibrosis were utilized. Levels of liver tissue injury-associated enzymes, including alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were monitored. $TGF-{\beta}1$ and the ${\alpha}$-smooth muscle actin (${\alpha}$-SMA) were measured as markers of the protective effects on hepatic fibrosis. The AST and ALT levels in blood were greatly enhanced by TAA and completely blunted by rutaecarpine. Rutaecarpine led to the down-regulation of $TGF-{\beta}$ and Bax mRNA expression, as well as the up-regulation of Bcl-2 and $Bcl-X_L$ mRNA levels. In conclusion, rutaecarpine inhibited TAA-induced hepatic fibrosis and apoptosis by inducing the expression of Bcl-2 while blocking $TGF-{\beta}1$ in our TAA-intoxicated model.

• Korean Journal of Pharmacognosy
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• v.40 no.1
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• pp.65-69
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• 2009

The present study investigated the antiproliferative effect of Litsea japonica in HL-60/ADR, adriamycin resistant human promyelocytic leukemia cells. The 80% ethanol extract of L. japonica markedly inhibited the growth of HL-60/ADR cells. When HL-60/ADR cells were treated with the extract, several apoptosis events like as DNA fragmentation, chromatin condensation and the increase of the population of sub-G1 hypodiploid cells were observed. In the mechanism of apoptosis induction by L. japonica, we examined the changes of Bcl-2 and Bax protein expression levels, and activation of caspases. After the HL-60/ADR cells were treated with the extract, the Bcl-2 expression was decreased, whereas the expression of Bax was increased in a time-dependent manner compared to the control. In addition, the active forms of caspase-9 and -3 were increased and the cleavage of poly (ADP-ribose) polymerase, a vital substrate of effector caspase, was observed. The results suggest that the inhibitory effect of L. japonica on the growth of the HL-60/ADR appears to arise from the induction of apoptosis via the down-regulation of Bcl-2 and the activation of caspases.

• Reproductive and Developmental Biology
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• v.36 no.3
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• pp.167-172
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• 2012

The key regulators of apoptosis are the interacting protein of the Bcl-2 family. Bcl-2, an important member of this family, blocks cytochrome C release by sequestering pro-apoptotic BH3-only proteins such as Bid, Bad, Bax and Bim. The pro-survival family members (Bcl-2, Bcl-XL, Bcl-W) are critical for cell survival, since loss of any of them causes cell death in certain cell type. However, its role during early porcine embryonic development is not sufficient. In this study, we traced the effects of Bcl-2 inhibitor, ABT-737, on early porcine embryonic development. We also investigated several indicators of developmental potential, including gene expression (apoptosis-related genes) and apoptosis, which are affected by ABT-737. Porcine embryos were cultured in the PZM-3 medium with or without ABT-737 for 6 days. In result, significant differences in developmental potential were detected between the embryos that were cultured with or without ABT-737 ($14.7{\pm}3.0$ vs $30.3{\pm}4.8%$, p<0.05). TUNEL assay showed that the number of containing fragmented DNA at the blastocyst stage increased in the ABT-737 treated group compared with control (4.7 vs 3.7, p<0.05). The mRNA expression of the pro-apoptotic gene Bax increased in ABT-737 treated group (p<0.05), whereas expressions of the anti-apoptotic Bcl-2 family members (Bcl-2, Bcl-XL, Bcl-W) decreased (p<0.05). Also, expressions of the ER stress indicator genes (GRP78, XBP-1 and sXBP-1) increased in ABT-737 treated group (p<0.05). In conclusion, Bcl-2 is closely associated with of apoptosis- and ER stress-related genes expressions and developmental potential in pig embryos.

• Journal of Life Science
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• v.17 no.11
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• pp.1596-1600
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• 2007

Bee venom is used to treat inflammatory diseases in Korean traditional medicine and has been known to inhibit proliferation and induce apoptosis in cancer cells. However, the molecular mechanisms involved in bee venom-induced apoptosis are still uncharacterized in human lung cancer cells. In the present study, we investigated the effects of bee venom on the apoptosis of A549 human lung epithelial cancer cells. Treatment of bee venom inhibited the cell viability and induced apoptosis in a concentration-dependent manner as measured by hemocytometer counts, fluorescence microscopy and flow cytometry analysis. Bee venom-induced apoptosis in A549 cells was associated with a marked inhibition of anti-apoptotic Bcl-2 expression without significant changes in the levels of Bax and Bcl-xL. Bee venom treatment also inhibited the levels of IAP family members such as cIAP-1 and cIAP-2 and induced the proteolytic activation of caspase-3 and caspase-9. Although further studies are needed, the present results suggest that apoptotic signals evoked by bee vemon in A549 cancer cells may converge caspases activation through a down-regulation of Bcl-2 rather than an up-regulation of Bax. These findings provide important insights into the possible molecular mechanisms of the anti-cancer activity of bee vemon in human cancer cells.

• Biomolecules & Therapeutics
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• v.22 no.4
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• pp.341-346
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• 2014

Paeonol is a major phenolic micromolecular component of Moutan cortex Radicis, a traditional Chinese Medicine. It has shown antitumor effects in previous studies; however, the underlying mechanisms remain unknown. This study investigated the mechanism by giving treatments of placebo, cyclophosphamide, paeonol of 150 and 300 mg/kg to 4 groups of mice bearing EMT6 breast cancer. Apoptosis in tumor cells were confirmed by morphology analysis, including hematoxylin, eosin staining and TUNEL staining. The results showed that the weight of EMT6 breast tumor was significantly reduced in the groups treated with both 150 and 300 mg/kg of paeonol. Immunohistochemical and Western blot results showed that the expression of Bcl-2 was down-regulated while the expression of Bax, caspase 8 and caspase 3 was up-regulated respectively. These results suggest that paeonol exhibits antitumor effects and the mechanism of the inhibition is via induction of apoptosis, regulation of Bcl-2 and Bax expression, and activation of caspase 8 and caspase 3.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.3023-3028
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• 2013

Objective: Photodynamic therapy (PDT ) is a promising modality for the treatment of various tumors. In order to assist in optimizing treatment, we applied 5-ALA/PDT in combination with low-dose cisplatin to evaluate cytotoxicity in Hela cells. Methods: Antiproliferative effects of 5-ALA/PDT and cisplatin, alone and in combination, were assessed using MTT assay. To examine levels of apoptosis, Hela cells treated with 5-ALA/PDT, and combination treatment were assessed with Annexin-V/PI by flow cytometry. To investigate the molecular mechanisms underlying alterations in cell proliferation and apoptosis, Western blot analysis was conducted to determine the expression of p53, p21, Bax and Bcl-2 proteins. Results: MTT assays indicated that combination treatment obviously decreased the viability of Hela cells compared to individual drug treatment. In addition, it was confirmed that exposure of Hela cells to 5-ALA/PDT in combination with low-dose cisplatin resulted in more apoptosis in vitro. Synergistic anticancer activity was related to upregulation p53 expression and alteration in expression of p21, Bcl-2 and Bax. Conclusion: Our findings suggest that administration of 5-ALA/PDT in combination with the low-dose cisplatin may be an effective and feasible therapy for cervical cancer.

• Journal of Chest Surgery
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• v.56 no.5
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• pp.295-303
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• 2023

Background: The use of Adriamycin (ADR), also known as doxorubicin, as a chemotherapy agent is limited by its detrimental adverse effects, especially cardiotoxicity. Recent studies have emphasized the crucial role of angiotensin II (Ang-II) in the development of ADR-induced cardiomyopathy. This study aimed to explore the potential cardioprotective effects of losartan in a rat model of ADR-induced cardiomyopathy. Methods: Male Sprague-Dawley rats were randomly divided into 3 groups: a control group (group C), an ADR-treated group (ADR 5 mg/kg/wk for 3 weeks via intraperitoneal injections; group A), and co-treatment of ADR with losartan group (same dose of ADR and losartan; 10 mg/kg/day per oral for 3 weeks; group L). Western blot analysis was conducted to demonstrate changes in brain natriuretic peptide, collagen 1, tumor necrosis factor (TNF)-α, interleukin-6, matrix metalloproteinase (MMP)-2, B-cell leukemia/lymphoma (Bcl)-2, Bcl-2-associated X (Bax), and caspase-3 protein expression levels in left ventricular (LV) tissues from each group. Results: Losartan administration reduced LV hypertrophy, collagen content, and the expression of pro-inflammatory factors TNF-α and MMP-2 in LV tissue. In addition, losartan led to a decrease in the expression of the pro-apoptotic proteins Bax and caspase-3 and an increase in the expression of the anti-apoptotic protein Bcl-2. Moreover, losartan treatment induced a reduction in the apoptotic area compared to group A. Conclusion: In an ADR-induced cardiomyopathy rat model, co-administration of ADR with losartan presented cardioprotective effects by attenuating LV hypertrophy, pro-inflammatory factors, and apoptosis in LV tissue.