• Title/Summary/Keyword: Changes to drug products

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Study of NIR in-line Monitoring of Physicochemical Changes during the Crystallization Process of Aspirin (Aspirin 결정화 과정 중 특성변화의 NIR 인라인 모니터링 연구)

  • Lee, Hea-Eun;Wang, In-Chun;Lee, Min-Jeong;Seo, Da-Young;Shin, Sangmun;Choi, Yongsun;Choi, Guang-Jin
    • Korean Chemical Engineering Research
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    • v.48 no.6
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    • pp.757-762
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    • 2010
  • Since the quality and performance of medicinal products are heavily dependent upon the size, shape and polymorphism of active pharmaceutical ingredients(APIs), their crystallization has been regarded as one of the most important pharmaceutical processes. In this study, NIR-based inline measurements were employed to monitor key attributes of API particles real-time during the crystallization process. Principal component analysis(PCA) method was selected to correlate inline NIR spectra while the well-known aspirin was studied as a model drug. According to our characterization results, the ratio of ethanol to acetone did not cause any change in polymorphism, but resulted in a significant difference in the nucleation time, crystal growth and crystal shape. These phenomenological changes were well correlated with the PCA's implications. It turned out that the NIR-based inline monitoring technology can be employed well in observing and predicting key quality attributes such as crystal size during pharmaceutical crystallization processes.

Discovering the Anti-cancer Effects of Ligusticum Chuanxiong through Network-based Pharmacology Analysis and Molecular Docking: An Inquiry into Natural Products (네트워크 기반 약리학 분석 및 분자 도킹을 통한 천궁의 항암 효과 예측: 천연물에 대한 탐구)

  • Do Kyung Han;Jee Won Shon;Eui Suk Sung;Youn Sook Kim;Won G. An
    • Journal of Life Science
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    • v.33 no.11
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    • pp.876-886
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    • 2023
  • In some cases of head and neck cancers (HNC), surgical interventions may result in the loss of organs and/or changes to their functions, thereby significantly affecting the patient's quality of life. As a result, the surgical treatment of HNC patients is often limited to specific cases, and alternative treatment modalities, such as chemotherapy, are considered. However, serious adverse effects caused by chemotherapy, such as severe nausea and vomiting, necessitate the need for the development of adjunctive methods to minimize patient suffering. Chuanxiong, Ligusticum chuanxiong (L. chuanxiong), is a natural herb used in Eastern medicine to treat cerebrovascular disorders and headaches. This study aimed to predict the effect and potential of L. chuanxiong as an auxiliary anticancer drug through network-based pharmacology and molecular docking analysis. The study results showed that 40 out of 41 genes of L. chuanxiong shared common targets of HNC and their proteins could be used to target HNC cells to prevent cancer progression. The results of the functional enrichment analysis confirmed that L. chuanxiong is associated with the neuroactive-ligand metabolism and neurotransmitter pathways, indicating its potential medicinal value as an adjuvant in HNC treatment. Lastly, our findings demonstrated that the active ingredient of L. chuanxiong, (Z)-Ligustilide, has the ATP binding site of heat shock protein 90, a protein known to promote the activation of cancer cells. These results suggest that L. chuanxiong is a promising candidate for developing auxiliary anticancer drugs, and further research could potentially lead to the discovery of newer and safer anti-cancer agents.

Interaction of Resveratrol and Genistein with Nucleic Acids

  • Usha, Subbiah;Johnson, Irudayam Maria;Malathi, Raghunathan
    • BMB Reports
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    • v.38 no.2
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    • pp.198-205
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    • 2005
  • Resveratrol (RES) and genistein (GEN) are the dietary natural products known to possess chemopreventive property and also the ability to repair DNA damage induced by mutagens/carcinogens. It is believed that the therapeutic activity of these compounds could be primarily due to their interaction with nucleic acids but detailed reports are not available. We here explore the interaction of these drugs with nucleic acids considering DNA and RNA as a potential therapeutic target. The interaction of RES and GEN has been analysed in buffered solution with DNA [saline sodium citrate (SSC)] and RNA [tris ethylene diammine tetra acetic acid (TE)] using UV-absorption and Fourier transform infrared (FTIR) spectroscopy. The UV analysis revealed lesser binding affinity with nucleic acids at lower concentration of RES (P/D = 5.00 and 10.00), while at higher drug concentration (P/D = 0.75, 1.00 and 2.50) hyperchromic effect with shift in the ${\lambda}_{max}$ is noted for DNA and RNA. A major RES-nucleic acids complexes was observed through base pairs and phosphate backbone groups with K = $35.782\;M^{-1}$ and K = $34.25\;M^{-1}$ for DNA-RES and RNA-RES complexes respectively. At various concentrations of GEN (P/D = 0.25, 0.50, 0.75, 1.00 and 2.50) hyperchromicity with shift in the ${\lambda}_{max}$ from 260 $\rightarrow$ 263 om and 260 $\rightarrow$ 270 nm is observed for DNA-GEN and RNA-GEN complexes respectively. The binding constant (from UV analysis) for GEN-nucleic acids complexes could not be obtained due to GEN absorbance overlap with that of nucleic acids at 260 nm. Nevertheless a detailed analysis with regard to the interaction of these drugs (RES/GEN) with DNA and RNA could feasibly be understood by FTIR spectroscopy. The NH band of free DNA and RNA which appeared at $3550-3100\;cm^{-1}$ and $3650-2700\;cm^{-1}$ shifted to $3450-2950\;cm^{-1}$ and $3550-3000\;cm^{-1}$ in DNA-RES and RNA-RES complexes respectively. Similarly shifts corresponding to $3650-3100\;cm^{-1}$ and $3420-3000\;cm^{-1}$ have been observed in DNA-GEN and RNA-GEN complexes respectively. The observed reduction in NH band of free nucleic acids upon complexation of these drugs is an indication of the involvement of the hydroxyl (OH) and imino (NH) group during the interaction of the drugs and nucleic acids (DNA/RNA) through H-bonded formation. The interaction of RES and GEN with bases appears in the order of G $\geq$ T > C > A and A > C $\geq$ T > G. Further interaction of these natural compounds with DNA and RNA is also supported by changes in the vibrational frequency (shift/intensity) in symmetrical and asymmetrical stretching of aromatic rings of drugs in the complex spectra. No appreciable shift is observed in the DNA and RNA marker bands, indicating that the B-DNA form and A-family conformation of RNA are not altered during their interaction with RES and GEN.

Fabrication of a Partial Genome Microarray of the Methylotrophic Yeast Hansenula polymorpha: Optimization and Evaluation of Transcript Profiling

  • OH , KWAN-SEOK;KWON, OH-SUK;OH, YUN-WI;SOHN, MIN-JEONG;JUNG, SOON-GEE;KIM, YONG-KYUNG;KIM, MIN-GON;RHEE, SANG-KI;GERD GELLISSEN,;KANG, HYUN-AH
    • Journal of Microbiology and Biotechnology
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    • v.14 no.6
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    • pp.1239-1248
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    • 2004
  • The methylotrophic yeast Hansenula polymorpha has been extensively studied as a model organism for methanol metabolism and peroxisome biogenesis. Recently, this yeast has also attracted attention as a promising host organism for recombinant protein production. Here, we describe the fabrication and evaluation of a DNA chip spotted with 382 open reading frames (ORFs) of H. polymorpha. Each ORF was PCR-amplified using gene-specific primer sets, of which the forward primers had 5'-aminolink. The PCR products were printed in duplicate onto the aldehyde-coated slide glasses to link only the coding strands to the surface of the slide via covalent coupling between amine and aldehyde groups. With the partial genome DNA chip, we compared efficiency of direct and indirect cDNA target labeling methods, and found that the indirect method, using fluorescent-labeled dendrimers, generated a higher hybridization signal-to-noise ratio than the direct method, using cDNA targets labeled by incorporation of fluorescence-labeled nucIeotides during reverse transcription. In addition, to assess the quality of this DNA chip, we analyzed the expression profiles of H. polymorpha cells grown on different carbon sources, such as glucose and methanol, and also those of cells treated with the superoxide­generating drug, menadione. The profiles obtained showed a high-level induction of a set of ORFs involved in methanol metabolism and oxidative stress response in the presence of methanol and menadione, respectively. The results demonstrate the sensitivity and reliability of our arrays to analyze global gene expression changes of H. polymorpha under defined environmental conditions.

Study on Single-dose Intramuscular Toxicity of Shinbaro Pharmacopuncture in Sprague-Dawley (SD) Rats and Beagle Dogs (신바로 약침의 SD 랫드와 비글견에 대한 단회 근육투여 독성시험)

  • Lee, Jin-Ho;Chung, Hwa-Jin;Lee, In-Hee;Lee, Jae-Woong;Kim, Eun-Jee;Kim, Min-Jeong
    • Journal of Korean Medicine Rehabilitation
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    • v.25 no.3
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    • pp.1-9
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    • 2015
  • Objectives To evaluate Shinbaro Pharmacopuncture safety through analysis of potential single-dose intramuscular toxicity of Sinbaro Pharmacopucture in SD rats and Beagle dogs. Methods Single-dose intramuscular toxicity of Shinbaro Pharmacopuncture was assessed in accordance with Korea Food and Drug Administration Guidelines for toxicity testing of Medicinal Products. The SD rats were treated intramuscularly with Shinbaro Pharmacopuncture at doses of 0, 4.6, 9.2, and 18.5 mg/kg, respectively. The Beagle dogs were treated intramuscularly with Shinbaro Pharmacopuncture at doses of 2.3, and 4.6 mg/kg, respectively, and after 3 days, the procedure was repeated a second time at doses of 0.6, and 1.2 mg/kg, respectively, for toxicity testing. Mortality, change in body weight, and necropsy findings were examined for the study period. Results There were no mortalities, general symptoms, or body weight changes in the SD rats. While pyelectasis of the left kidney was observed in a male rat in the 4.6 mg/kg administration group, natural occurrence is common, and does not appear to be related with the test substance. No mortalities were observed in the Beagle dogs. In assessment of general symptoms, a female dog in the 9.2 mg/kg group displayed body weight decrease due to leftover food, but the change in body weight was within the normal range seen at 6~7 months, and the necropsy findings were not significant. The toxicity of the test substance appears to be minimal. Conclusions The results suggest that the lethal dose 50 ($LD_{50}$) and approximate lethaldose (ALD) value in single intramuscular administration of Shinbaro Pharmacopuncture in SD rats and Beagle dogs are higher than 18.5 mg/kg.

The food and nutrient intakes from daily processed food in Korean adults: based on the 6th Korea National Health and Nutrition Examination Survey data (2013~2015) (한국 성인의 가공식품으로부터의 식품 및 영양소 섭취량 평가 : 제 6기 (2013~2015) 국민건강영양조사를 바탕으로)

  • Ha, Ae Wha;Kim, Woo Kyoung
    • Journal of Nutrition and Health
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    • v.52 no.5
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    • pp.422-434
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    • 2019
  • Purpose: The consumption of processed foods has recently been increasing due to changes in the living environment. The purpose of this study was to identify the contribution of processed food to the nutrient intake of adult Koreans. Methods: A total of 15,760 adult people in the $6^{th}$ National Health and Nutrition Examination Survey (2013 ~ 2015) were included in this study. According to the Korea Food and Drug Administration's classification criteria for processed foods, the 24 hour dietary recall data of the subjects were classified as processed food or natural food. The processed food intake, nutrient intake and major processed food sources by food groups were analyzed. Results: Men consumed more processed foods than did the women. Consumption of processed foods decreased with age, but it increased with the education level and the income level. The total daily processed food intake accounted for 68.1% of the total food intake. The food groups with high processed food intake were beverage, vegetables, cereals and grain products, fruits, and milk and dairy products in this order. The top food source of each food groups were beer, kimchi, bread, processed apple products, and milk. After adjusting for age, gender, and energy intake, all the nutrient intakes and percentage of dietary reference intakes for Koreans, except carbohydrates, were significantly higher in processed foods than in natural foods. The sodium intake from the processed food was 96.3% of total daily sodium intake. The intakes of nutrients from processed foods, excluding vitamins C, dietary fiber, iron, and vitamin A, were higher in men than in women. The intake of sodium from processed foods was highest for people of 30 ~ 49 years of age, and the intake of sodium from processed foods decreased for people over 50. Conclusion: Korean adults consumed more processed food than the natural food, consuming more calories and most of the nutrients from the processed food overall total daily intakes. The intake of processed foods is expected to further increase in the future, and nutritional education and research on the ingestion and selection of healthy processed foods are necessary.

AN EXPERIMENTAL STUDY ON THE EFFECT OF Ca(OH)2 UPON THE HEALING PROCESS OF THE PULP AND PERIAPICAL TISSUE IN THE DOGS' TEETH (수산화칼슘이 손상치수조직 및 치근조직의 치유에 미치는 영향에 관한 연구)

  • Lim, S.S.;Yoon, S.H.;Lee, C.S.;Lee, M.J.;Kim, Y.H.;Kwon, H.C.;Um, C.M.
    • Restorative Dentistry and Endodontics
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    • v.8 no.1
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    • pp.123-131
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    • 1982
  • The purpose of this study was to observe the responses of the remaining pulp tissue after pulpotomy upon the several kinds of $Ca(OH)_2$ products and the responses of periapical tissue upon some root canal filling materials after extirpation. For pulpotomy, the class V cavities were prepared on the premolars, molars and upper canines, and the pulp was amputated. Each drug was placed over the amputated tissue and cavity was sealed with zinc oxide eugenol cement. The drugs which were used for the study were Dycal (Caulk Co. U.S.A.), Cavitec (Kerr Co. U.S.A.), Calvital, Nobudyne and Neodyne (Neo Dental Chemical Products). For extirpation, the endodontic cavities were prepared on the lingual surfaces of anterior teeth, and the pulp tissues were extirpated as routine method. After enlarging, irrigation, and measuring of root length by taking X-ray, each root canal filling material was filled in the canal with gutta percha cone, and endodontic cavity was sealed with zinc oxide eugenol cement. Zinc oxide eugenol, $Ca(OH)_2$ (Eli Lilly Co. U.S.A.) and Vitapex (Neo Dental Chemical Products) were used as root canal filling materials. Animals were sacrificed after 1, 3 and 6 weeks following the operation. The teeth were decalcified in formic acid, sectioned and stained with hematoxylin eosin. Microscopic examination revealed as follows. 1. Dycal: The dentin bridge formation was observed at the 3rd week after pulpotomy. Inflammatory conditions which were infiltration of inflammatory cells and dilatation of blood vessels were kept in remaining pulp tissue at the 6th week. 2. Calvital: The dentin bridge was observed at the 1st week after pulpotomy. As the time clasped, the pulp tended to be the fibrous degeneration. 3. Cavitec, Nobudyne and Neodyne: In the case of Cavitec and Nobudyne, the incompleted and irregular dentin bridge was observed at the 6th week, and in Neodyne, was observed at the 3rd week. The severe inflammatory changes were seen in the remaining pulp tissue. As the time clasped, the fibrous degeneration tended to spread in the remaining pulp tissue. 4. $Ca(OH)_2$: Osteocementum was formed at the 3rd week, the matrix of cementum and dentin were resorted, and infiltration of lymphocytes was seen in periapical tissue when $Ca(OH)_2$ was used as canal-filling materials. S. ZOE and Vitapex The cementum like substance was seen in periapical portion at the 1st week, when ZOE and Vitapex were used as root canal filling materials. As the time elapsed, the matrix of cementum and dentin tended to be resorted. At the 6th week, the inflammatory condition of periapical tissue was continued in the case of ZOE, but was reduced in the case of Vitapex.

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Global Cosmetics Trends and Cosmceuticals for 21st Century Asia (화장품의 세계적인 개발동향과 21세기 아시아인을 위한 기능성 화장품)

  • T.Joseph Lin
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.23 no.1
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    • pp.5-20
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    • 1997
  • War and poverty depress the consumption of cosmetics, while peace and prosperity encourage their proliferation. With the end of World War II, the US, Europe and Japan witnessed rapid growth of their cosmetic industries. The ending of the Cold War has stimulated the growth of the industry in Eastern Europe. Improved economies, and mass communication are also responsible for the fast growth of the cosmetic industries in many Asian nations. The rapid development of the cosmetic industry in mainland China over the past decade proves that changing economies and political climates can deeply affect the health of our business. In addition to war, economy, political climate and mass communication, factors such as lifestyle, religion, morality and value concepts, can also affect the growth of our industry. Cosmetics are the product of the society. As society and the needs of its people change, cosmetics also evolve with respect to their contents, packaging, distribution, marketing concepts, and emphasis. In many ways, cosmetics mirror our society, reflecting social changes. Until the early 70's, cosmetics in the US were primarily developed for white women. The civil rights movement of the 60's gave birth to ethnic cosmetics, and products designed for African-Americans became popular in the 70's and 80's. The consumerism of the 70's led the FDA to tighten cosmetic regulations, forcing manufacturers to disclose ingredients on their labels. The result was the spread of safety-oriented, "hypoallergenic" cosmetics and more selective use of ingredients. The new ingredient labeling law in Europe is also likely to affect the manner in which development chemists choose ingredients for new products. Environmental pollution, too, can affect cosmetics trends. For example, the concern over ozone depletion in the stratosphere has promoted the consumption of suncare products. Similarly, the popularity of natural cosmetic ingredients, the search of non-animal testing methods, and ecology-conscious cosmetic packaging seen in recent years all reflect the profound influences of our changing world. In the 1980's, a class of efficacy-oriented skin-care products, which the New York Times dubbed "serious" cosmetics, emerged in the US. "Cosmeceuticals" refer to hybrids of cosmetics and pharmaceuticals which have gained importance in the US in the 90's and are quickly spreading world-wide. In spite of regulatory problems, consumer demand and new technologies continue to encourage their development. New classes of cosmeceuticals are emerging to meet the demands of increasingly affluent Asian consumers as we enter the 21st century. as we enter the 21st century.

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Effects of Nutrition Education Program Based on Social Cognitive Theory for Low Sodium Consumption among Housewives Living in Certain Regions of Seoul (서울시 일부 지역 주부의 나트륨 섭취 감소를 위한 사회인지이론 기반의 영양 교육 프로그램의 적용 및 평가)

  • Baek, Jae Yeon;Yi, Hae-Yeon;Hwang, Ji-Yun;Kim, Kirang
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.46 no.10
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    • pp.1243-1252
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    • 2017
  • There are limited programs for low sodium intake based on the nutrition education model for housewives who cook family meals. The objective of this study was to evaluate the effects of model-based nutrition programs for low sodium intake among housewives residing in Seoul by incorporating social cognitive theory. A questionnaire survey before and after education was conducted on 140 housewives who participated in the 'Low Sodium Nutritional Education Program' delivered by a district public health center for 12 weeks from November 2015 to January 2016. The contents of the nutrition education program and program evaluation items were based on the action plans for 'Less Sodium Healthy Practice' suggested by the Ministry of Food and Drug Safety. The results show that program participants showed a lower preference for sodium, higher selection of low sodium dishes from restaurants or cafeteria if available, and increased awareness of the need of restaurants to serve low sodium dishes compared to before. In terms of behavioral changes, there were significant improvements in checking nutrition labeling and selection of foods with low sodium, use of low sodium food products, use of natural seasonings to reduce salt intake, and consumption of fast foods and processed foods. On the other hand, requesting less salty meals when ordering and introducing restaurants or cafeterias with healthy and low sodium menus turned out to be difficult to put into practice. In conclusion, the nutrition education program for sodium intake reduction for housewives was effective in increasing knowledge, environment recognition, and behaviors related to low sodium intake but not behaviors related to physical environmental factors. Therefore, further nutrition education programs and practices for sodium intake reduction should be comprehensively implemented with improvement of physical environments for low sodium intake.

A Novel Chenodeoxycholic Derivative HS-1200 Enhances Radiation-induced Apoptosis in Human MCF-7 Breast Cancer Cells (담즙산 합성유도체(HS-1200)가 인체 유방암 세포주(MCF-7)에서 유도하는 방사선 감작 효과)

  • Lee Hyung Sik;Choi Young Min;Kwon Hyuk Chan;Song Yeon Suk
    • Radiation Oncology Journal
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    • v.22 no.2
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    • pp.145-154
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    • 2004
  • Purpose : To examine whether a synthetic bile acid derivatives (HS-1200) sensitizes the radiation-induced apoptosis in human breast cancer cells (MCF-7) and to investigate the underlying mechanism. Materials and Methods : Human breast cancer cells (MCF-7) in exponential growth phase were treated with HS-1200 for 24 hours at 37$^{\circ}C$ with 5$\%$ CO$_{2}$ in air atmosphere. After removal of HS-1200, cells were irradiated with 2$\~$8 Gy X-ray, and then cultured Ii drug-free media for 24-96 hours. The effect of radiation on the clonogenicity of MCF-7 cells was determined with clonogenic cell survival assay with 16$\mu$M of HS-1200. The induction of apoptosis was determined using agarose gel electrophoresis and Hoechst staining. The expression level of apoptosis-related molecules, such as PARP, Bax, Bcl-2, Bak and AIF, were assayed by Western blotting analysis with 40$\mu$M of HS-1200 combined with 8 Gy irradiation. To examine the cellular location of cytochrome c, bax and AIF immunofluorescent stainings were undertaken. Results : Treatment of MCF-7 cells with 40$\mu$M of HS-1200 combined with 8 Gy irradiation showed several changes associated with enhanced apoptosis by agarose gel electrophoresis and Hoechst staining. HS-1200 combined with 8 Gy irradiation treatment also enhanced production of PARP cleavage products and increased Bax/Bcl-2 ratio by Western blotting. Loss of mitochondrial membrane potential ($\Delta$$\psi$$_{m}$) and increased cytochrome c staining indicated that cytochrome c had been released from the mitochondria in HS-1200 treated cells. Conclusion : We demonstrated that combination treatment with a synthetic chenodeoxycholic acid derivative HS-1200 and irradiation enhanced radiation-induced apoptosis of human breast cancer cells (MCF-7). We suggest that the increased Bax/Bcl-2 ratio In HS-1200 co-treatment group underlies the increased radio sensitivity of MCF-7 cells. Further futures studies are remained elusive.