• Journal of Microbiology and Biotechnology
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• 제29권11호
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• pp.1799-1805
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• 2019

Doxorubicin (DOX) is one of the most effective anticancer agents used for the treatment of multiple cancers; however, its use is limited by its short half-life and adverse drug reactions, especially cardiotoxicity. In this study, we found that the conjugate of DOX with APTA12 (Gemcitabine incorporated G-quadruplex aptamer) was significantly more cancer selective and cytotoxic than DOX. The conjugate had an affinity for nucleolin, with higher uptake and retention into the cancer cells than those of DOX. Further, it was localized to the nucleus, which is the target site of DOX. Owing to its mechanism of action, DOX has the ability to intercalate into the nucleotides thus making it a suitable drug to form a conjugate with cancer selective aptamers such as APTA12. The conjugation can lead to selectively accumulate in the cancer cells thus decreasing its potential nonspecific as well as cardiotoxic side effects. The aim of this study was to prepare a conjugate of DOX with APTA12 and assess the chemotherapeutic properties of the conjugate specific to cancer cells. The DOX-APTA12 conjugate was prepared by incubation and its cytotoxicity in MCF-10A (non-cancerous mammary cells) and MDA-MB-231 (breast cancer cells) was assessed. The results indicate that DOX-APTA12 conjugate is a potential option for chemotherapy especially for nucleolin expressing breast cancer with reduced doxorubicin associated side effects.

• 한국환경과학회지
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• 제27권9호
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• pp.771-780
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• 2018

To develope a microbial weed control agent, HCN-producing bacteria were isolated, and their characteristics were investigated. A selected strain of WA15 was identified as Pseudomonas koreensis by morphological, cultural, biochemical and 16S rRNA gene analyses. The conditions for HCN production was investigated by a One-Variable-at-a-Time (OVT) method. The optimal HCN production conditions were tryptone 1%, glycine 0.06%, NaCl 1%, and an initial pH and temperature of 5.0 and $30^{\circ}C$, respectively. The major component for HCN production was glycine. Under optimal conditions, HCN production was about 3 times higher than that of the basal medium. The WA15 strain had physiological activities, such as indoleacetic acid that was associated with the elongation of plant roots and siderophore and ammonification inhibiting fungal growth, and produced hydrolytic enzymes, such as cellulase, pectinase and lipase. The strain was able to inhibit the growth of phytopathogenic fungi, such as Rhizoctonia solani, Botrytis cinerea and Fusarium oxysporum, by the synergistic action of volatile HCN and diffusible antimicrobial compounds. A microscopic observation of R. solani that was teated with the WA15 strain showed morphological abnormalities of fungal mycelia, which could explain the role of the antimicrobial metabolites that were produced by the WA15 strain. The volatile HCN produced by the WA15 strain was also found to have insecticidal activity against termites. Our results indicate that Pseudomonas koreensis WA15 can be applied as a microbial agent for weed control and also as a termite repellent. Furthermore, it could be applied as a microbial termiticidal agent to replace synthetic insecticides.

• BMB Reports
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• 제48권8호
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• pp.461-466
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• 2015

Epigallocatechin gallate (EGCG) and curcumin are well known to naturally-occurring anticancer agents. The aim of this study was to verify the combined beneficial anticancer effects of curcumin and EGCG on PC3 prostate cancer cells, which are resistant to chemotherapy drugs and apoptosis inducers. EGCG showed weaker inhibitory effect on PC3 cell proliferation than two other prostate cancer cell lines, LNCaP and DU145. Co-treatment of curcumin improved antiproliferative effect of EGCG on PC3 cells. The protein expressions of p21 were significantly increased by the co-treatment of EGCG and curcumin, whereas it was not changed by the treatment with each individual compound. Moreover, treatments of EGCG and curcumin arrested both S and G2/M phases of PC3 cells. These results suggest that the enhanced inhibitory effect of EGCG on PC3 cell proliferation by curcumin was mediated by the synergic up-regulation of p21-induced growth arrest and followed cell growth arrest. [BMB Reports 2015; 48(8): 461-466]

• Asian Pacific Journal of Cancer Prevention
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• 제14권10호
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• pp.6089-6094
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• 2013

Berberine, a common isoquinoline alkaloid, has been shown to possess anti-cancer activities. However, the underlying molecular mechanisms are still not completely understood. In the current study, we investigated the effects of berberine on cell growth, colony formation, cell cycle distribution, and whether it improved the anticancer efficiency of cisplatin and doxorubicin in human breast cancer estrogen receptor positive (ER+) MCF-7 cells and estrogen receptor negative (ER-) MDA-MB-231 cells. Notably, berberine treatment significantly inhibited cell growth and colony formation in the two cell lines, berberine in combination with cisplatin exerting synergistic growth inhibitory effects. Accompanied by decreased growth, berberine induced G1 phase arrest in MCF-7 but not MDA-MB-231 cells. To provide a more detailed understanding of the mechanisms of action of berberine, we performed genome-wide expression profiling of berberine-treated cells using cDNA microarrays. This revealed that there were 3,397 and 2,706 genes regulated by berberine in MCF-7 and MDA-MB-231 cells, respectively. Fene oncology (GO) analysis identified that many of the target genes were involved in regulation of the cell cycle, cell migration, apoptosis, and drug responses. To confirm the microarray data, qPCR analysis was conducted for 10 selected genes based on previously reported associations with breast cancer and GO analysis. In conclusion, berberine exhibits inhibitory effects on breast cancer cells proliferation, which is likely mediated by alteration of gene expression profiles.

• BMB Reports
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• 제31권1호
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• pp.83-88
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• 1998

Recently a B cell surface molecule, CD40, has emerged as a receptor mediating a co-stimulatory signal for B cell proliferation and differentiation. To investigate the mechanism of synergy between interleukin-4 (IL-4) and CD40 ligation in B cell activation, we have examined the effect of CE40 cross-linking on the IL-4 receptor expression in human B cells using anti-CE40 antibody. We observed that IL-4 and anti-CD40 both induce IL-4 receptor gene expression with a rapid kinetics resulting in a noticeable accumulation of IL-4 receptor mRNA within 4 h. While IL-4 caused a dose-dependent induction of surface IL-4 receptor expression, the inclusion of anti-CD40 in the IL-4-treated culture, further up-regulated the IL-4-induced IL-4 receptor expression as analyzed by flow cytometry. Pretreatment of B cells with inhibitors of protein tyrosine kinase (PTK) resulted in a significant inhibition of both the IL-4- and anti-CD40-induced IL-4 receptor mRNA levels, while protein kinase C (PKC) inhibitors had no effects. These results suggest that IL-4 and CD40 ligation generate B cell signals, which via PTK-dependent pathways, lead to the synergistic induction of IL-4 receptor gene expression. The rapid induction of IL-4 receptor gene expression through the tyrosine kinase-mediated signal transduction by B cell activating stimuli, would provide cells capacity for an efficient response to IL-4 in the early phase of IL-4 action, and may in part constitute the molecular basis of the reported anti-CD40 co-stimulatory effect on the IL-4-induced response.

• Interdisciplinary Bio Central
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• 제5권2호
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• pp.3.1-3.7
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• 2013

Recently, the productivity of drug discovery has gradually decreased as the limitations of single-target-based drugs for various and complex diseases become exposed. To overcome these limitations, drug combinations have been proposed, and great efforts have been made to predict efficacious drug combinations by statistical methods using drug databases. However, previous methods which did not take into account biological networks are insufficient for elaborate predictions. Also, increased evidences to support the fact that drug effects are closely related to metabolic enzymes suggested the possibility for a new approach to the study drug combinations. Therefore, in this paper we suggest a novel approach for analyzing drug combinations using a metabolic network in a systematic manner. The influence of a drug on the metabolic network is described using the distance between the drug target and an enzyme. Target-enzyme distances are converted into influence scores, and from these scores we calculated the correlations between drugs. The result shows that the influence score derived from the targetenzyme distance reflects the mechanism of drug action onto the metabolic network properly. In an analysis of the correlation score distribution, efficacious drug combinations tended to have low correlation scores, and this tendency corresponded to the known properties of the drug combinations. These facts suggest that our approach is useful for prediction drug combinations with an advanced understanding of drug mechanisms.

• 대한한의학방제학회지
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• 제10권2호
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• pp.1-4
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• 2002

The development of Korean Oriental medicine is based upon the accumulation of experience and knowledge gathered over the centuries. The approaches taken are holistic and empirical. There is a need to understand their actions at molecular levels with more rational, objective and scientific studies. Today it appears that Chronic and age-associated diceases may be multifactorial and hence more complex. A different approach may be required. One claimed usage of Korean Oriental medicine is for the treatment and prevention of chronic and age-associated illnesses. Some of the botanical formulas used for this purpose were discovered thousands of years ago and continue to be used today. There are indications that these formulas may indeed be helpful in the treatment or prevention of chronic diseases. This multi-component medicine could not only be very useful meeting the unmet clinical needs but for defining a more synergistic therapy that supports and maintains the bodies natural curative abilities. The potential usefulness of Korean Oriental medicine embodies the belief of maintaining healthy homeostasis of the body through the proper balance of a mixture of chemical at different organs or tissues. This concept is different from western medicine and implies that multiple compounds may act on multiple mechanisms of action to maintain the balance of the complex web of biology. This is very important in view of sciences current direction to integrate fragmented information to develop future medicines. The western and eastern approaches to human health and disease are complementary to each other. The best approach in developing future medicines is to integrate both approaches.

• Journal of Plant Biology
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• 제35권1호
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• pp.77-84
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• 1992

오옥신의 작용이 PKC에 의한 단백질의 인산화 과정과 연관되어 있는지 확인하기 위하여 PKC를 활성화시키는 물질인 DAG와 TPA 그리고 오옥신이 옥수수 자엽초의 신장에 미치는 효과를 조사하였다. DAG와 TPA를 옥수수 자엽초에 처리하면 DAG는 최대 500%까지, TPA는 최대 300%까지 자엽초 생장율을 증가시켰다. 이때 IAA나 TPA 각각에 의한 생장율 증가의 합(최대 800%)보다도 TPA와 IAA를 함께 처리한 조직의 생장율 증가가 더 커서(최대 1200%) TPA와 IAA는 상승효과를 나타내었다. 전기영동을 통하여 TPA와 IAA를 처리한 자엽초 세포질의 단백질 인산화 정도를 비교한 결과 TPA+IAA>IAA>TPA>control의 순서대로 단백질의 인산화가 증가했다. 이러한 단백질 인산화의 증가와 신장 생장과의 관계를 명확히 하기 위해 PKC 억제제로 알려진 STA를 자엽초에 처리한 결과 TPA의 존재에 관계없이 생장율이 80%까지 저해되었다. 이와 같은 실험 결과들은 IAA에 의한 자엽초 신장 촉진 과정의 적어도 한 단계에 동물의 PKC와 유사할 것으로 추측되는 PKC에 의한 단백질 인산화가 연관되어 있을 가능성이 있다고 생각하게 한다.

• Journal of Microbiology
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• 제45권5호
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• pp.431-440
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• 2007

A silkworm (Bombyx mori L.) extract known to contain naturally occurring iminosugars, including 1-deoxynojirimycin (1-DNJ) derived from the mulberry tree (Morus alba L.), was evaluated in surrogate HCV and HBV in vitro assays. Antiviral activity of the silkworm extract and one of its purified constituents, 1-DNJ, was demonstrated against bovine viral diarrhea virus (BVDV) and GB virus-B (GBV-B), both members of the Flaviviridae family, and against woodchuck hepatitis virus (WHV) and hepatitis B virus (HBV), both members of the Hepadnaviridae family of viruses. The silkworm extract exhibited a 1,300 fold greater antiviral effect against BVDV in comparison to purified 1-DNJ. Glycoprotein processing of BVDV envelope proteins was disrupted upon treatment with the naturally derived components. The glycosylation of the WHV envelope proteins was affected largely by treatment with the silkworm extract than with purified 1-DNJ as well. The mechanism of action for this therapy may lie in the generation of defective particles that are unable to initiate the next cycle of infection as demonstrated by inhibition of GBV-B in vitro. We postulate that the five constituent iminosugars present in the silkworm extract contribute, in a synergistic manner, toward the antiviral effects observed for the inhibition of intact maturation of hepatitis viral particles and may complement conventional therapies. These results indicate that pre-clinical testing of the natural silkworm extract with regards to the efficacy of treatment against viral hepatitis infections can be evaluated in the respective animal models, in preparation for clinical trials in humans.

• Preventive Nutrition and Food Science
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• 제12권4호
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• pp.197-201
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• 2007

Genistein is an active component of legumes and other related food shown to be associated with prevention of degenerative diseases such as cancer through inducing signaling pathways. Treatment of genistein resulted in the induction of apoptosis in the cultured cancer cells. This induction of apoptosis was demonstrated by the Tunel assay in these cells. Unveiling the potential of genistein in cytotoxicity via apoptosis when it is treated with estrogen can predict the therapeutic capability of genistein in breast cancers in the presence of endogenous estrogen. We have found that apoptosis induced by genistein treatment in the presence of estrogen is agonistic or antagonistic depending on the concentrations and treatment periods applied in MCF-7 breast cancer cells. For the suppression of cell survival, 24 hr of treatment was required to induce a synergistic agonistic response between estrogen and genistein at low concentrations of genistein. After this period, the agonistic pattern of genistein to estrogen disappeared. The decrement of COX-2 expression in MCF-7 cells treated with genistein was accompanied with the activation of AMPK only at a high concentration of genistein. This association between AMPK activation and down-regulation of COX-2 by genistein was dampened in the presence of estrogen. It was also demonstrated that genistein and estrogen regulate cell survival and apoptosis by modulating p53 and caspase-3 in the opposite direction. These results suggest that genistein has the potential to control breast cancer development, and co-treatment with estrogen can cause agonistic or antagonistic action on breast cancer cell control.