• Asian Pacific Journal of Cancer Prevention
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• 제16권4호
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• pp.1501-1506
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• 2015

Gemcitabine is an anti-cancer drug with clinically uses in the treatment of various neoplasms, including breast, ovarian, non-small cell lung, pancreaticand cervical cancers, T-cell malignancies, germ cell tumours, and hepatocellular carcinomas. However, it has also been reported to have many adverse effects. Naturally occurring anti-mutagenic effects, especially those of plant origin, have recently become a subject of intensive research. The present study was therefore designed to investigate the anti-mutagenic effects of Salvia merjamie (Family: Lamiaceae) plant extracts against the mutagenic effects of gemcitabine. The anti-mutagenic properties of Salvia merjamie were tested in Inbred SWR/J male and female mice bone marrow cells. The mice were treated in four groups; a control group treated with 30 mg/kg body weight gemcitabine and three treatment groups, each with 30 mg/kg body weight gemcitabine together with, respectively, 50, 100 and 150 mg/kg body weight Salvia merjamie extract. Chromosomal aberration and mitotic index assays were performed with the results demonstrating that Salvia merjamie extract protects bone marrow cells in mice against gemcitabine induced mutagenicity. This information can be used for the development of a potential therapeutic anti-mutagenic agents.

• Journal of Pharmaceutical Investigation
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• 제37권5호
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• pp.305-309
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• 2007

Arsenic compounds have been used to treat various diseases including cancer in oriental medicine. Arsenic trioxide ($As_2O_3,\;Trisenox^{(R)}$) has been used for the treatment of leukemia and its anti-solid tumor activity has also been reported recently. Tetra-arsenic oxide ($As_4O_6,\;TetraAs^{(R)}$) is a newly developed arsenic compound which has shown an anticancer activity in some human cancer cell lines. The purpose of this study was to evaluate the anti-gastric cancer potential of TetraAs and to search for an agent with synergistic interaction with TetraAs against human gastric cancers. We analysed anti-proliferative effect of TetraAs when given alone and in combination with other chemotherapeutic agents such as 5-FU, paclitaxel, and cisplatin in SNU-216, a human gastric cancer cell line. The $IC_{50}$ of these 4 anti-cancer drugs ranged from 5.8 nM to $7.5\;{\mu}M$ with a potency rank of order paclitaxel>TetraAs>cisplatin>5-FU. TetraAs showed 10-fold greater potency than 5-FU and cisplatin at the same effect level of $IC_{50}$. TetraAs+5-FU and TetraAs+paclitaxel showed synergistic and additive interaction, respectively. On the other hand, TetraAs with cisplatin group appeared to be strongly antagonistic. Apoptotic population was measured and compared between single and combination treatment. The apoptotic cells for the combination of TetraAs+5-FU showed significant increase compared to single TetraAs treatment. On the contrary, TetraAs+cisplatin showed less apoptotic cells compared to TetraAs or cisplatin alone treatment. Overall, our results indicate that TetraAs can be effectively combined with 5-FU or paclitaxel, but not with cisplatin for synergistic anti-cancer effect, which warrants further evaluation using in vivo models.

• 동의생리병리학회지
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• 제29권2호
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• pp.195-201
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• 2015

The aim of the study is to investigate the anti-cancer effects of Scutellaria barbata in AGS human gastric adenocarcinoma cells. MTT (3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide) assay and caspase 3 or 9 activity assay were carried out to examine cell death with Scutellaria barbata. To elucidate the inhibitory effects of Scutellaria barbata, cell cycle (sub-G1) analysis and mitochondrial membrane potential were performed in AGS cells after 24 h incubation with Scutellaria barbata. Scutellaria barbata induced apoptosis in AGS cells by using the MTT assay, the sub-G1 analysis and mitochondrial membrane potential assay. The stronger inhibition effects of AGS cell growth was observed by application of Scutellaria barbata combined with several anti-cancer drugs (paclitaxel, 5-fluorouracil, cisplatin, ectoposide, doxorubicin and docetaxel) in comparison to the application of Scutellaria barbata or anti-cancer drugs. Our findings provide insight into unraveling the effects of Scutellaria barbata in human gastric cancer cells and developing therapeutic agents against gastric cancer.

• 대한한의학방제학회지
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• 제23권1호
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• pp.101-110
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• 2015

Objectives : The purpose of this study was to investigate the anti-cancer effects of Oldenlandia diffusa extract on WiDr human colorectal adenocarcinoma cells. Methods : We examined cell death by (3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide) MTT assay and the caspase 3 and 9 activity assay with Oldenlandia diffusa extract. To examine the inhibitory effects of Oldenlandia diffusa extract, we performed a cell cycle (sub-G1) analysis and mitochondrial membrane potential for the WiDr cells after 24 hours with Oldenlandia diffusa extract. Results : 1. Oldenlandia diffusa extract induced cell death in WiDr cells. 2. The sub-G1 peak was increased by Oldenlandia diffusa extract in WiDr cells. 3. Oldenlandia diffusa extract leads to increase the mitochondrial membrane depolarization in WiDr cells. 4. Oldenlandia diffusa extract increases caspase 3 and 9 activities in WiDr cells. 5. Oldenlandia diffusa extract combined with several anti-cancer drugs (paclitaxel, 5-fluorouracil, cisplatin, ectoposide, doxorubicin and docetaxel) markedly inhibited the growth of WiDr cells compared to Oldenlandia diffusa extract and anti-cancer drugs alone. Conclusions : Oldenlandia diffusa extract has an apoptotic role in human colorectal cancer cells and a potential role in developing therapeutic agents against colorectal cancer.

• Biomolecules & Therapeutics
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• 제12권2호
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• pp.122-128
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• 2004

Since reactive oxygen species, prostaglandins, and nitric oxide are closely involved in various pathological conditions anti play important roles in the initiation, promotion, and progression of carcinogenesis, agents that modulate the production or activity of them might be considered as cancer chemopreventive agents. In the present study, we evaluated chemopreventive potential of some grape shoot extracts and their refined materials using various in vitro assay systems. As a result, both grape shoot extracts and refined materials possessed effective radical scavenging activities about 70~80% at the concentration of 500 ${\mu}$g/ml, and especially the Sheridan shoot extract showed the most potent 1, 1-diphenyl-2-picrylhydrazyl radical scavenging activity that was similar to resveratrol. In addition, refined materials from grape shoot extracts suppressed lipopolysaccharide-induced nitric oxide production in macrophage cells, anti refined materials from Kyoho and Campbell shoot extracts exhibited similar inhibitory activities with $IC_{50}$ value of 224 ${\mu}$g/ml and 285 ${\mu}$g/ml, respectively. In addition, at the concentration of 50 ${\mu}$g/ml, all of refined materials inhibited cell proliferation against various human cancer cells about 30~40% compared to control. These findings suggest that grape shoot extract and their refined materials might be useful sources for the development of chemopreventive agents and/or functional foods.

• The Korean Journal of Physiology and Pharmacology
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• 제23권5호
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• pp.393-402
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• 2019

Aurora kinases inhibitors, including ZM447439 (ZM), which suppress cell division, have attracted a great deal of attention as potential novel anti-cancer drugs. Several recent studies have confirmed the anti-cancer effects of ZM in various cancer cell lines. However, there have been no studies regarding the cardiac safety of this agent. We performed several cytotoxicity, invasion and migration assays to examine the anti-cancer effects of ZM. To evaluate the potential effects of ZM on cardiac repolarisation, whole-cell patch-clamp experiments were performed with human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and cells with heterogeneous cardiac ion channel expression. We also conducted a contractility assay with rat ventricular myocytes to determine the effects of ZM on myocardial contraction and/or relaxation. In tests to determine in vitro efficacy, ZM inhibited the proliferation of A549, H1299 (lung cancer), MCF-7 (breast cancer) and HepG2 (hepatoma) cell lines with $IC_{50}$ in the submicromolar range, and attenuated the invasive and metastatic capacity of A549 cells. In cardiac toxicity testing, ZM did not significantly affect $I_{Na}$, $I_{Ks}$ or $I_{K1}$, but decreased $I_{hERG}$ in a dose-dependent manner ($IC_{50}$: $6.53{\mu}M$). In action potential (AP) assay using hiPSC-CMs, ZM did not induce any changes in AP parameters up to $3{\mu}M$, but it at $10{\mu}M$ induced prolongation of AP duration. In summary, ZM showed potent broad-spectrum anti-tumor activity, but relatively low levels of cardiac side effects compared to the effective doses to tumor. Therefore, ZM has a potential to be a candidate as an anti-cancer with low cardiac toxicity.

• BMB Reports
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• 제36권3호
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• pp.269-274
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• 2003

In the fight against cancer, novel chemotherapeutic agents are constantly being sought to complement existing drugs. Various studies have presented evidence that the apoptosis that is induced by these anticancer agents is implicated in tumor regression, and Bcl-2 family genes play a part in apoptosis following treatment with various stimuli. Here, we present data that a styrylpyrone derivative (SPD) that is extracted from the plant Goniothalamus sp. showed cytotoxic effects on the human breast cancer cell line MCF-7. SPD significantly increased apoptosis in MCF-7 cells, as visualized by phase contrast microscopy and evaluated by the Tdt-mediated dUTP nick end-labeling assay and nuclear morphology. Western blotting and immunostaining revealed up-regulation of the proapoptotic Bax protein expression. SPD, however, did not affect the expression of the anti-apoptotic protein, Bcl-2. These results, therefore, suggest SPD as a potent cytotoxic agent on MCF-7 cells by inducing apoptosis through the modulation of Bax levels.

• IMMUNE NETWORK
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• 제20권4호
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• pp.29.1-29.20
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• 2020

The development of refractory tumor cells limits therapeutic efficacy in cancer by activating mechanisms that promote cellular proliferation, migration, invasion, metastasis, and survival. Benzimidazole anthelmintics have broad-spectrum action to remove parasites both in human and veterinary medicine. In addition to being antiparasitic agents, benzimidazole anthelmintics are known to exert anticancer activities, such as the disruption of microtubule polymerization, the induction of apoptosis, cell cycle (G2/M) arrest, anti-angiogenesis, and blockage of glucose transport. These antitumorigenic effects even extend to cancer cells resistant to approved therapies and when in combination with conventional therapeutics, enhance anticancer efficacy and hold promise as adjuvants. Above all, these anthelmintics may offer a broad, safe spectrum to treat cancer, as demonstrated by their long history of use as antiparasitic agents. The present review summarizes central literature regarding the anticancer effects of benzimidazole anthelmintics, including albendazole, parbendazole, fenbendazole, mebendazole, oxibendazole, oxfendazole, ricobendazole, and flubendazole in cancer cell lines, animal tumor models, and clinical trials. This review provides valuable information on how to improve the quality of life in patients with cancers by increasing the treatment options and decreasing side effects from conventional therapy.

• The Korean Journal of Pain
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• 제33권2호
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• pp.108-120
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• 2020

From the perspective of the definition of pain, pain can be divided into emotional and sensory components, which originate from potential and actual tissue damage, respectively. The pharmacologic treatment of the emotional pain component includes antianxiety drugs, antidepressants, and antipsychotics. The anti-anxiety drugs have anti-anxious, sedative, and somnolent effects. The antipsychotics are effective in patients with positive symptoms of psychosis. On the other hand, the sensory pain component can be divided into nociceptive and neuropathic pain. Non-steroidal anti-inflammatory drugs (NSAIDs) and opioids are usually applied for somatic and visceral nociceptive pain, respectively; anticonvulsants and antidepressants are administered for the treatment of neuropathic pain with positive and negative symptoms, respectively. The NSAIDs, which inhibit the cyclo-oxygenase pathway, exhibit anti-inflammatory, antipyretic, and analgesic effects; however, they have a therapeutic ceiling. The adverse reactions (ADRs) of the NSAIDs include gastrointestinal problems, generalized edema, and increased bleeding tendency. The opioids, which bind to the opioid receptors, present an analgesic effect only, without anti-inflammatory, antipyretic, or ceiling effects. The ADRs of the opioids start from itching and nausea/vomiting to cardiovascular and respiratory depression, as well as constipation. The anticonvulsants include carbamazepine, related to sodium channel blockade, and gabapentin and pregabalin, related to calcium blockade. The antidepressants show their analgesic actions mainly through inhibiting the reuptake of serotonin or norepinephrine. Most drugs, except NSAIDs, need an updose titration period. The principle of polypharmacy for analgesia in case of mixed components of pain is increasing therapeutic effects while reducing ADRs, based on the origin of the pain.

• 한국자원식물학회지
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• 제30권6호
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• pp.640-646
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• 2017

In this study, we elucidated anti-cancer activity and potential molecular mechanism of 70% ethanol extracts from Taxilli Ramulus (Taxillus chinensis (DC.) Danser) (TR-E70) against human colorectal cancer cells. Anti-cell proliferative effect of TR-E70 was evaluated by MTT assay. The effect of TR-E70 on the expression of cyclin D1 in the protein and mRNA level was evaluated by Western blot and RT-PCR, respectively. TR-E70 suppressed the proliferation of human colorectal cancer cell lines, HCT116 and SW480. Although TR-E70 decreased cyclin D1 expression in protein and mRNA level, decreased level of cyclin D1 protein by TR-E70 more dramatically occurred than that of cyclin D1 mRNA. Cyclin D1 downregulation by TR-E70 was attenuated in presence of MG132. In addition, TR-E70 phosphorylated threonine-286 (T286) of cyclin D1. TR-E70-mediated cyclin D1 degradation was blocked in presence of LiCl as an inhibitor $GSK3{\beta}$ but not PD98059 as an ERK1/2 inhibitor and SB203580 as a p38 inhibitor. Our results suggest that TR-E70 may downregulate cyclin D1 as one of the potential anti-cancer targets through $GSK3{\beta}$-dependent cyclin D1 degradation. From these findings, TR-E70 has potential to be a candidate for the development of chemoprevention or therapeutic agents for human colorectal cancer.