• BMB Reports
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• v.43 no.11
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• pp.750-755
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• 2010

Crude Orostachys japonicus polysaccharide extract (OJP) was prepared by hot steam extraction. Polysaccharides (OJPI) were separated from OJP by gel filtration chromatography and phenol-sulfuric acid assay. The average molecular weight of the OJPI was 30-50 kDa. The anti-proliferative effect of OJPI on HT-29 human colon cancer cells was investigated via morphology study, cell viability assay, apoptosis assay, cell cycle analysis, and cDNA microarray. OJPI inhibited proliferation and growth of HT29 cells and also stimulated apoptosis in a dose- and time-dependent manner. In cell cycle analysis, treatment with OJPI resulted in a marked increase of cells in the G0 (sub G1) and G2/M phases. To screen for genes involved in the induction of cell cycle arrest and apoptosis, the gene expression profiles of HT-29 cells treated with OJPI were examined by cDNA microarray, revealing that a number of genes were up- or down-regulated by OJPI. Whereas several genes involved in anti-apoptosis, cell proliferation and growth, and cell cycle regulation were down-regulated, expression levels of several genes involved in apoptosis, tumor suppression, and other signal transduction events were up-regulated. These results suggest that OJPI inhibits the growth of HT-29 human colon cancer cells by various apoptosis-aiding activities as well as apoptosis itself. Therefore, OJPI deserve further development as an effective agent exhibiting anticancer activity.

• Molecules and Cells
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• v.26 no.4
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• pp.344-349
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• 2008

5-Fluorouracil (5-FU), a pyrimidine antagonist, has a long history in cancer treatment. The targeted pyrimidine biosynthesis pathway includes dihydropyrimidine dehydrogenase (DPD), which converts 5-FU to an inactive metabolite, and thymidylate synthase (TS), which is a major target of 5-FU. Using Caenorhabditis elegans as a model system to study the functional and resistance mechanisms of anti-cancer drugs, we examined these two genes in order to determine the extent of molecular conservation between C. elegans and humans. Overexpression of the worm DPD and TS homologs (DPYD-1 and Y110A7A.4, respectively) suppressed germ cell death following 5-FU exposure. In addition, DPYD-1 depletion by RNAi resulted in 5-FU sensitivity, while treatment with Y110A7A.4 RNAi and 5-FU resulted in similar patterns of embryonic death. Thus, the pathway of 5-FU function appears to be highly conserved between C. elegans and humans at the molecular level.

• The Journal of Internal Korean Medicine
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• v.33 no.2
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• pp.197-208
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• 2012

Objectives : Gleditsiae Spina has the effects of expelling toxins, draining pus, invigorating blood and resolving abscesses. Some clinicians apply the herb for patients suffering from cancer. However, its anti-cancer activities are not well understood. In the present study, anti-tumor agents from Gleditsiae Spina were purified. Methods : The viability of the PC-3 cell line was determined using MTT assay, and the induction of apoptosis by Gleditsiae Spina extract in PC-3 cells was measured by Annexin-V/propidium iodide double staining assay detected by flow cytometry. TLC and HPLC analysis were used to separate and identify the anti-cancer agents. Results : Treatment of the extract resulted in significant decreased cell viability of PC-3 cells in a dose- and time-dependent manner. Dose-dependent apoptotic cell death was also measured by flow cytometry analysis. The anti-cancer agents were successfully separated and identified by using TLC and HPLC analysis and the most potential agent among them was separated from EtOAC fraction. Conclusions : These results might be applied in developing new drugs from natural resources like Korean traditional medicine, and also support the clinical usefulness of herbal medicine.

• YAKHAK HOEJI
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• v.46 no.5
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• pp.352-357
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• 2002

The three crude drugs of the Kalopanax pictus (Araliaceae) roots (K), Pueraria thunbergiana (Leguminosae) flowers (P), and the Rhus verniciflua (Anacardiaceae) heartwood(R) used for anti-thirst drugs in Oriental herb medicine were extracted with MeOH, respectively, and the successive fractionation of the extract gave EtOAc extract. Certain amount ratios of the three extracts were also prepared to compare the antimutagenicity in Ames test. In N-methyl-N(-nitro-N-nitrosoguanidine (MNNG; 0.4 (g/plate)-induced test, the activities of complex mixture were observed between the highest antimutagenic activity of K extract and the lowest P extract. In aflatoxin (AFB$_1$)-induced test, the EtOAc complex (K : P : R=l : 1 : 3) labeled E-113 decreased the revertants of Salmonella typhimurium TA100 by 95％, which activity were highest among other extracts or complexes mixture used. Fractionation of organic solvent mostly increased the antimutagenicity. These trends were also observed in the antimutagenicity test of the mixture of each active component of kalopanaxsaponin A, tectorigenin and sulfuretin. These results supported that many kinds of anti-thirst herb medicine in the prescription could effectively prevent cancer disease.

• BMB Reports
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• v.50 no.8
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• pp.401-410
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• 2017

The protein disulfide isomerase (PDI) family is a group of multifunctional endoplasmic reticulum (ER) enzymes that mediate the formation of disulfide bonds, catalyze the cysteine-based redox reactions and assist the quality control of client proteins. Recent structural and functional studies have demonstrated that PDI members not only play an essential role in the proteostasis in the ER but also exert diverse effects in numerous human disorders including cancer and neurodegenerative diseases. Increasing evidence suggests that PDI is actively involved in the proliferation, survival, and metastasis of several types of cancer cells. Although the molecular mechanism by which PDI contributes to tumorigenesis and metastasis remains to be understood, PDI is now emerging as a new therapeutic target for cancer treatment. In fact, several attempts have been made to develop PDI inhibitors as anti-cancer drugs. In this review, we discuss the properties and diverse functions of human PDI proteins and focus on recent findings regarding their roles in the state of diseases including cancer and neurodegeneration.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6709-6714
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• 2013

Background: Breast cancer is a leading cause of death in women. The available chemotherapy drugs have been associated with many side effects. Bromelain has novel medicinal qualities including anti-inflammatory, anti-thrombotic, fibrinolytic and anti-cancer functions. Commercially available bromelain is obtained through tedious methods; therefore, recombinant bromelain may provide a cheaper and simpler choice with similar quality. Materials and Methods: This study aimed to assess the effects of commercial and recombinant bromelain on the cytokinetic behavior of MCF-7 breast cancer cells and their potential as therapeutic alternatives in cancer treatment. Cytotoxic activities of commercial and recombinant bromelain were determined using (sulforhodamine) SRB assay. Next, cell viability assays were conducted to determine effects of commercial and recombinant bromelain on MCF-7 cell cytokinetic behavior. Finally, the established growth kinetic data were used to modify a model that predicts the effects of commercial and recombinant bromelain on MCF-7 cells. Results: Commercial and recombinant bromelain exerted strong effects towards decreasing the cell viability of MCF-7 cells with $IC_{50}$ values of 5.13 ${\mu}g/mL$ and 6.25 ${\mu}g/mL$, respectively, compared to taxol with an $IC_{50}$ value of 0.063 ${\mu}g/mL$. The present results indicate that commercial and recombinant bromelain both have anti-proliferative activity, reduced the number of cell generations from 3.92 to 2.81 for commercial bromelain and to 2.86 for recombinant bromelain, while with taxol reduction was to 3.12. Microscopic observation of bromelain-treated MCF-7 cells demonstrated detachment. Inhibition activity was verified with growth rates decreased dynamically from 0.009 $h^{-1}$ to 0.0059 $h^{-1}$ for commercial bromelain and to 0.0063 $h^{-1}$ for recombinant bromelain. Conclusions: Commercial and recombinant bromelain both affect cytokinetics of MCF-7 cells by decreasing cell viability, demonstrating similar strength to taxol.

• The Korean Journal of Physiology and Pharmacology
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• v.7 no.5
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• pp.255-259
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• 2003

Dendritic cells (DCs) play a critical role in various immune responses involving $CD4^+$ T cells and have been used to generate anti-tumor immunity. Chemotherapy induces severe side effects including immunosuppression in patients with cancer. Although immunosuppression has been studied, the effects of anticancer drugs on DCs are not fully determined. In this study, we demonstrated that CD40 activation strongly protected DCs from 5-fluorouracil (5-FU) or mitomycin C-induced apoptosis. DCspecific surface markers, including CD11c and major histocompatibility complex (MHC) class II, were used for identifying DCs. CD 40 activation with anti-CD40 mAb significantly enhanced the viability of DCs treated with 5-FU or mitomycin C, assayed by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide). Fluorescence staining and analysis clearly confirmed the enhancing effect of anti-CD40 mAb on the viability of DCs, suggesting that CD40 activation may transduce critical signals for the viability of DCs. Annexin V staining assay showed that CD40 significantly protected DCs from 5-FU or mitomycin C-induced apoptosis. Taken together, this study shows that CD40 activation with anti-CD40 mAb has strong anti-apoptosis effect on DCs, suggesting that CD40 activation may overcome the immunosuppression, especially downregulation of number and function of DCs in chemotherapy-treated cancer patients.

• Proceedings of the Plant Resources Society of Korea Conference
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• 1999.10a
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• pp.90-109
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• 1999

Many plant species are used in Malaysia in folk medicine for the treatment of cancer. This paper presents some of these species with details on other ethnopharmacological uses, the known bioactivities and some chemical constituents of each of the species given. It is normal practice in traditional medicine that one species of plant is used to treat various ailments. Thus the plant species listed are all used to treat cancer but have various other ethnophrmacological uses as well, some with few other uses and rest with many other uses. Information on bioactivities of each species resulting from tests on human and experimental animals are also given. Proven bioactivities give strength to ethnopharmacological claims on the efficacies of plant resources in the treatment of cancer and various other ailments but will but will not necessarily lead to the production of new pharmaceutical drugs. Many of the known chemical constituents of each species are given. This shows the richness and variety of chemicals containes in each of the species listed, The chemicals listed may or may not prove to be important in the pharmaceutical sciences but is an indication of what each species contatin in thrms of plant chemicals, It is a well known fact that many of the pharmaceutical prescriptions in present day use are of plant origin and semi-synthetic or fully synthetic chemicals produced using knowledge gained from studies of phytochemicals. Thus the paper presented will give useful information and also shows the richness of plant species that have high potentials for the development of anti-cancer resources from plants in Malaysia.

• Biomedical Science Letters
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• v.25 no.4
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• pp.293-301
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• 2019

Combination chemotherapy is more effective than mono-chemotherapy and is widely used in clinical practice for enhanced cancer treatment. In this study, we investigated the potential synergistic effects of acetaminophen, a common component in many cold medicines, and romidepsin, a histone deacetylase (HDAC) inhibitor, in the A549 non-small cell lung cancer (NSCLC) cell line. The combination of acetaminophen and romidepsin also exerted significant cytotoxicity and apoptosis induced by activation of caspase-3 on tumor cells in vitro. Moreover, combination therapy significantly induced increased production of chemokines that stimulate migration of activated T-cells into tumor cells. This mechanism can lead to active T-cell mediated anti-tumor immunity in addition to the direct cytotoxic chemotherapeutic effect. Activated T-cells led to enhanced cytotoxicity in drug-treated A549 cells through interaction with tumor cells. These results suggested that the interaction between the two drugs is synergistic and significant. In conclusion, our data showed that the use of romidepsin and low concentrations acetaminophen could induce effective anti-tumor effects via enhanced tumor immune and direct cytotoxic chemotherapeutic responses. The combination of acetaminophen with romidepsin should be considered as a promising strategy for the treatment of lung cancer.

• The Journal of Internal Korean Medicine
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• v.29 no.2
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• pp.490-499
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• 2008

Objectives : This study was aimed to elucidate the effects of Trichosanthes kirilowii extract (TKE) on the angiogenesis and growth of tumor cells. Methods : Tube formation assay was performed by using human umbilical vein endothelial cells (HUVEC), and anchorage dependent colony assay was performed by using B16-F10 melanoma, Hep G2 and HT1080, CT-26 and SNU-1 cells. Results : For HUVEC, TKE at a level of more than 100 ${\mu}g/m{\ell}$ suppresses cell growth. For HUVEC at 100 ${\mu}g/m{\ell}$ and greater TKE density, the formation of tubes was suppressed in a dose-dependant manner. TKE controls the colony formations of B16-F10 melanoma cells, CT 26 cells, and Hep G2 cells, and its effect is proportional to density. In HT1080 cells and SNU-1 cells, formation is suppressed regardless of density. Conclusions : From these results, it could be concluded that TKE has significant properties on anti-angiogenesis and growth inhibiting of tumor cells. It is suggested that TKE will be a good candidate for new drugs or therapeutics for anti-angiogenesis.