• Archives of Pharmacal Research
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• 제8권3호
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• pp.159-168
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• 1985

In attempt to develop a drug delivery system using serum albumin microspheres, bovine serum albumin microspheres containing antitumor agent, cytarabine, were prepared. The shape, surface characteristics, size distribution, behavior of in vitro distribution, drug release behaior, and degradation of albumin microspheres in animal liver tissue homogenate and proteolytic enzyme were investigated. The shape of albumin microspheres was spherical and the surface was smooth and compact. The size distribution of the albumin microspheres was affected by dispersion forces during emulsification and albumin concentration. Distribution of albumin mirospheres after intravenous administration in rabbit was achieved immediately. In vitro, albumin microsphere matrix was so hard that it retained most of cytarabine except initial burst during the first 10 minutes, and the level of drug release during the initial burst was affected by heating temperature, drug/albumin concentration ratio and size distribution. After drug release test, the morphology of albumin micropheres was not changed. Albumin microsphere matrix was degraded by the rabbit liver tissue homogenate and proteolytic enzyme. The degree of degradation was affected by heating temperature.

• 대한약침학회지
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• 제22권1호
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• pp.7-15
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• 2019

Portulaca oleracea L. (PO) or Purslane is an annual grassy plant that is distributed in many parts of the world, especially the tropical and subtropical areas. PO has some pharmacological properties such as analgesic, antibacterial, skeletal muscle-relaxant, wound-healing, anti- inflammatory and a radical scavenger. This review article is focused on the anti-inflammatory, immuno-modulatory, anti-oxidant and anti-tumor activities of the PO. Anti-inflammatory, immuno-modulatory, anti-oxidant and Anti-tumor effects of PO were searched using various databases until the end of August 2018. The online literature was searched using PubMed, Science Direct, Scopus, Google Scholar and Web of Science. Our review showed that PO exerts its effects through anti-inflammatory properties and balancing the adaptive and innate immune system depending on situations. PO acts as immune-modulator and anti-oxidant agent in both inflammatory states by the dominance of Th2 response such as asthma, cancer and atopic dermatitis and evoked Th1 disorders including hepatitis and multiple sclerosis.

• 대한약침학회지
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• 제22권2호
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• pp.55-67
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• 2019

The incidences of cancer are continuously increasing worldwide, affecting life of millions of people. Several factors associated with the internal and external environment are responsible for this deadly disease. The key internal determinants like abnormal hormonal regulation, genetic mutations and external determinants such as lifestyle and occupational factors enhances onset of cancer. From the ancient time, plants were remained as the most trusted source of medicine for the treatment of diverse disease conditions. Extensive studies have been performed for the discovery of effective anticancer agent from the plant and still it is going on. Pentacyclic triterpenoids are biologically active phytochemicals having a different range of activities such as anti-inflammatory, hepatoprotective, anti-hypertensive, antiulcerogenic and anti-tumor. These compounds generally contain ursane, oleanane, lupane and friedelane as a chief skeleton of pentacyclic triterpenoids which are generally present in higher plants. Isoprene unit, phytochemical, with good antitumor/anticancer activity is required for the biosynthesis of pentacyclic triterpenoids. Mechanisms such as cytotoxicity, DNA polymerase inhibition, regulation of apoptosis, change in signal transductions, interfere with angiogenesis and dedifferentiation, antiproliferative activity and metastasis inhibition are might be responsible for their anticancer effect. Present review spotlights diverse targets, mechanisms and pathways of pentacyclic triterpenoids responsible for anticancer effect.

• Journal of Microbiology and Biotechnology
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• 제32권6호
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• pp.718-729
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• 2022

Esophageal squamous cell carcinoma (ESCC) is the most common primary esophageal malignancy with poor prognosis. Here, due to the necessity for exploring potential therapies against ESCC, we obtained the gene expression data on ESCC from the TCGA and GEO databases. Venn diagram analysis was applied to identify common targets. The protein-protein interaction network was constructed by Cytoscape software, and the hub targets were extracted from the network via cytoHubba. The potential hub nodes as drug targets were found by pharmacophore-based virtual screening and molecular modeling, and the antitumor activity was evaluated through in vitro studies. A total of 364 differentially expressed genes (DEGs) in ESCC were identified. Pathway enrichment analyses suggested that most DEGs were mainly involved in the cell cycle. Three hub targets were retrieved, including CENPF, CCNA2 (cyclin A), and CCNB1 (cyclin B1), which were highly expressed in esophageal cancer and associated with prognosis. Moreover, amentoflavone, a promising drug candidate found by pharmacophore-based virtual screening, showed antiproliferative and proapoptotic effects and induced G1 in esophageal squamous carcinoma cells. Taken together, our findings suggested that amentoflavone could be a potential cell cycle inhibitor targeting cyclin B1, and is therefore expected to serve as a great therapeutic agent for treating esophageal squamous cell carcinoma.

• 폴리머
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• 제26권5호
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• pp.691-700
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• 2002

항암제가 함유된 생분해성 고분자 디바이스를 이용한 국소전달요법은 종양 부위에 고농도로 약물을 전달시킬 수 있는 이유로 약물의 효율성을 증가시킬 수 있다. 1,3-bis(2-chloroethyl)-1-nitro-sourea (BCNU, carmustine)는 뇌종양 치료를 위하여 가장 일반적으로 사용되는 화학요법적 약물이다. 표적 부위까지 항암제를 효과적으로 전달하기 위한 이식제의 설계는 중요한 인자이다. 본 연구에서 약물의 방출경향을 조절하기 위해서 생분해성 웨이퍼의 첨가제와 다양한 제형 변화로부터 BCNU의 방출패턴을 조사하였다. 각각 3.85, 10, 20 및 30%의 BCNU를 함유한 PLGA 웨이퍼를 다양한 형태(직경 3, 5 및 10 mm, 두께 0.5, 1 및 2 mm)로 직접 압축성형법에 의해 제조하였다. 생체외 방출실험에서 BCNU 함유 PLGA 웨이퍼로부터 약물 방출거동은 웨이퍼의 포기 약물 함유량, 무게, 직경, 두께, 부피, 표면적 및 PLGA 분자량뿐만 아니라 첨가제의 종류와 같은 다양한 변수로 조절했다. 웨이퍼로부터 약물의 방출은 BCNU 함유량 및 염화나트륨 (NaCl)과 폴리엔비닐피롤리돈 (PVP)이 증가할수록 촉진되었다. 또한, BCNU가 함유된 PLGA 웨이퍼의 무게와 형태변화에 대한 조사를 통하여 다양한 기하학적 인자들과 첨가제의 효과를 고찰하였다.

• Natural Product Sciences
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• 제13권1호
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• pp.1-5
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• 2007

Dietary flavonoids have antioxidant and antitumor promoting effects. Rhus verniciflua Stokes (RVS) is a flavonoid-rich herbal medicine and has long been used as a food additive and an antitumor agent in Korea. Previous study demonstrated that a purified flavonoid fraction prepared from RVS, herein named RCMF (the RVS chloroform-methanol fraction), exhibited growth inhibition and induced apoptosis in human osteosarcoma(HOS) cells. This study evaluated if p53-mediated pathway is associated with the RCMF-induced apoptosis in HOS cells. RCMF was shown to be capable of inducing apoptosis of the cells, as expected, and transparently increased p53 expression in the cells. However, the RCMF-induced cytotoxicity was suppressed by transfecting the cells with antisense p53 oligonucleotide, which also inhibited the decrease of Bcl-2 and the increase of Bax in mitochondria, and the release of cytochrome c into cytosol. This finding suggests that p53-mediated mitochondrial stress is required for RCMF-induced apoptosis in HOS cells.

• 대한본초학회지
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• 제30권1호
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• pp.33-42
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• 2015

Objectives : The aim of this study was to evaluate the antitumor effects of Cheongpyesagan-tang(CST) and YKK012 on colon cancer. Methods : MTT assay was used to evaluate the cytotoxicity of Single herbs and combinations of CST and YKK012 on murine colon cancer cells, Colon 38. To explain effects of apoptosis in colon cancer, we performed the western blot. Effects of CST and YKK012 on antitumor activity of CPT-11 using the murine colon38 allograft tumor in BDF1 mice. Results : Single herbs and combinations of CST and YKK012 was tested in vitro, Rhei Radix (RH) and Scutellariae Radix (SC) and YKK012 showed dose-response cytotoxicity on Colon 38. This might be due to the apoptosis, as we see Bax and Caspase-3, which are apoptotic factors, was expressed in RH and SC treated cells. YKK012 also showed increased expression of Caspase-3. In mouse colorectal cancer xenograft model of colon38 cells, herbal combinations showed tendencies of tumor regression, but was not significant. Furthermore, because toxicity was observed in CST group, we reduced the dose of CST for the next experiment. The anti-tumor effects of herbal combinations were insufficient to be used as single anti-tumor agent. With simultaneous usage of CPT-11, contrary to that CST showed no synergistic effects, YKK012 which was composed by the combination of four $ER{\beta}$ selective herbs, significantly reduced the size of tumor and Bax expression was increased. Conclusions : We suggest YKK012 can be a effective cancer adjuvant therapy with CPT-11 on colon cancer.

• 동의생리병리학회지
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• 제20권6호
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• pp.1530-1537
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• 2006

Platycodi Radix, the root of Platycodon grandiflorum A. DC (Campanulaceae), commonly known as Doraji in Korea (Chinese name, 'Jiegeng', and Japanese name, 'Kikyo') has been used as an expectorant in traditional Oriental medicine. Extracts from the roots of P. grandiflorum have been reported to have wide ranging health benefits. In Korea, Platycodi Radix is also used as a food and employed as a folk remedy for adult diseases, such as bronchitis, asthma and pulmonary tuberculosis, hyperlipidemia, diabetes, and inflammatory diseases, and as a sedative. Several studies on its chemical and immunopharmacological effects including immunostimulation and antitumor activity have been performed. However, the relevant molecular mechanisms are poorly understood. Platycodi Radix, the root of Platycodon grandiflorum A. DC (Campanulaceae), commonly known as Doraji in Korea (Chinese name, 'Jiegeng', and Japanese name, 'Kikyo') has been used as an expectorant in traditional Oriental medicine. Extracts from the roots of P. grandiflorum have been reported to have wide ranging health bensfits. In Korea, Platycodi Radix is also used as a food and employed as a folk remedy for adult diseases, such as bronchitis, asthma and pulmonary tuberculosis, hyperlipidemia, diabetes, and inflammatory diseases, and as a sedative. Several studies on its chemical and immunopharmacological effects including immunostimulation and antitumor activity have been performed. However, the relevant molecular mechanisms are poorly understood. In the present study, we investigated the effects of an aqueous extract from the roots of P. grandiflorum AEPG) on the cell growth of human lung adenocarcinoma NCI-H460 cells in order to understand its anti-proliferative mechanism. AEPG treatment down-regulated the cyclin D1 expression in both transcriptional and translational levels without alteration of cyclin E. In AEPG-treated cells, the levels of cyclin-dependent kinase (C아) 6 mRNA and protein were significantly inhibited, but the levels of Cdk2 and Cdk4 were slightly inhibited by treatment of AEPG. AEPG treatment induced a marked accumulation of Cdk inhibitors, p16 and p27. However, AEPG treatment did not affect not only retinoblastoma protein (pRB) but also tumor suppressor p53 protein expression. The present results indicated that AEPG-induced inhibition of lung cancer cell proliferation is associated with the blockage of G1 phase progression through induction of Cdk inhibitors such as p16 and p27, and inhibition of cyclin D1 and Cdk6. AEPG exposure, as offered by this study, provides cluse for the mechanism of AEPG action. Taken together, these findings suggest that P. grandiflorum has strong potential for development as an agent for prevention and treatiment against human lung cancer.

• Asian Pacific Journal of Cancer Prevention
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• 제14권4호
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• pp.2487-2490
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• 2013

In Thai traditional medicine, Plumbago indica or Jetamul-Pleung-Dang in Thai is known to have health benefit especially for anti-inflammatory, antibacterial, and antitumor activities. However, the mechanisms of its action are still uncertain. One of which might be genotoxic effects. In the present study, we investigated the genotoxicity of an ethanolic extract of Plumbago indica root (EEPIR) by sister chromatid exchange (SCE) assay in human lymphocytes. Results have shown that all treatments with EEPIR ($12.5-100{\mu}g/ml$) could induce cell cycle delay as shown by significant increase in the number of metaphase cells in the first cell cycle but neither in the second nor the third cell cycle. Only at concentrations of 25, 50, and $100{\mu}g/ml$ were SCE levels significantly increased above that of the control (p<0.05). EEPIR at a concentration of $500{\mu}g/ml$ induced cell death as few mitotic cells were shown. Accordingly, EEPIR ($25-100{\mu}g/ml$) is genotoxic in human lymphocytes and cytotoxic at concentrations of ${\geq}500{\mu}g/ml$ in vitro. Therefore, these activities of the EEPIR could serve its potential therapeutic effects, especially as an anticancer agent. Further study of EEPIR in vivo is now needed to support this in vitro evidence.

• Asian Pacific Journal of Cancer Prevention
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• 제14권6호
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• pp.3909-3919
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• 2013

The aim of the present investigation was to evaluate the effect of A ferruginea extract on Dalton's lymphoma ascites (DLA) induced tumours in BALB/c mice. Experimental animals received A ferruginea extract (10 mg/kg.b.wt) intraperitoneally for 14 consecutive days after DLA tumor challenge. Treatment with extract significantly increased the life span, total white blood cell (WBC) count and haemoglobin (Hb) content and decreased the level of serum aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), gamma glutamyl transferase (${\gamma}$-GT) and nitric oxide (NO) in DLA bearing ascites tumor models. In addition, administration of extract significantly decreased the tumour volume and body weight in a DLA bearing solid tumor model. The levels of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-${\alpha}$), interleukin-1 beta (IL-$1{\beta}$), interleukin-6 (IL-6) and granulocyte monocyte-colony stimulating factor (GM-CSF), as well as pro-angiogenic growth factors such as vascular endothelial growth factor (VEGF) and inducible nitric oxide synthase (iNOS) were elevated in solid tumour controls, but significantly reduced by A ferruginea administration. On the other hand, the extract stimulated the production of interleukin-2 (IL-2) and interferon-gamma (IFN-${\gamma}$) in animals with DLA induced solid tumours. Increase in $CD4^+$ T-cell population suggested strong immunostimulant activity for this extract. GC/MS and LC/MS analysis showed quinone, quinoline, imidazolidine, pyrrolidine, cyclopentenone, thiazole, pyrazole, catechin and coumarin derivatives as major compounds present in the A ferruginea methanolic extract. Thus, the outcome of the present study suggests that A ferruginea extract has immunomodulatory and tumor inhibitory activities and has the potential to be developed as a natural anticancer agent.