• Title/Summary/Keyword: Cytotoxic effect

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Growth Inhibitory Effect of Extracts of Propolis on Epithelial Ovarian Cancer Cells (상피성 난소암 세포에서 프로폴리스 추출물의 세포 증식 저해 효과)

  • Yang, Ga Ram;Yoon, Kyung Mi;Oh, Hyun Ho;Kim, Min Sung;Hwang, Tae Ho;An, Won Gun
    • Journal of Life Science
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    • v.27 no.7
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    • pp.834-839
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    • 2017
  • Propolis is a natural product collected from plants by honey bees product used extensively in traditional medicine for its antioxidant, anti-inflammatory, immunomodulatory and anti-cancer effects. Propolis exhibits a broad spectrum of biological activities because it is a complex mixture of natural substances. Ovarian cancer is the second most common newly diagnosed cancer from all cancers among women in Korea and the leading cause of death from gynecological malignancies. While most ovarian cancer patients initially respond to surgical debulking and chemotherapy, patients later succumb to the disease. Thus, there is an urgent need to test novel therapeutic agents to counteract the high mortality rate associated with ovarian cancer. In this study, we investigated the anti-cancer properties and the active mechanism of Australian propolis in human epithelial ovarian cancer A2780 cells. Our data revealed that propolis showed a cytotoxic activity in a dose-dependent manner. Flow cytometric analysis for cell cycle arrest and apoptosis using propidium iodide staning and annexin V-FITC indicated that propolis could induce cycle arrest in the G0/G1 phase and apoptosis in a dose-dependent manner on human epithelial ovarian cancer cells. These results suggest that the Australian propolis is potential alternative agent on ovarian cancer prevention and treatment.

Induction of Apoptotic Cell Death by Aqueous Extract of Cordyceps militaris Through Activation of Caspase-3 in Human Hepatocarcinoma Hep3B Cells (Hep3B 간암세포에서 Caspase-3 활성화를 통한 동충하초 열수추출물의 Apoptosis 유도에 관한 연구)

  • Kim, Kyung-Mi;Park, Cheol;Seo, Sang-Ho;Hong, Sang-Hoon;Lee, Won-Ho;Choi, Yung-Hyun
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.37 no.6
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    • pp.714-720
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    • 2008
  • Cordyceps militaris is a medicinal fungus which has been used for patient suffering from cancer in Oriental medicine. It was previously reported that C. militaris extracts are capable of inhibiting tumor growth and inducing apoptosis; however, the anti-poliferative effects of human cancer cells have been poorly understood. In this study, to elucidate the anti-cancer mechanisms of human cancer cells by treatment with aqueous extract of C. militaris (AECM), we investigated the anti-proliferative effects of AECM in human hepatocarcinoma Hep3B cells. AECM treatment inhibited the growth of Hep3B cells and induced the apoptotic cell death in a concentration-dependent manner such as formation of apoptotic bodies and increased populations of apoptotic-sub G1 phase. The induction of apoptosis by AECM was connected with a proteolytic activation of caspase-3 and caspase-8. and concomitant degradation of poly (ADP-ribose) polymerase (PARP) and ${\beta}$-catenin proteins. Furthermore, caspase-3 inhibitor, z-DEVD-fmk, significantly inhibited AECM-induced apoptosis demonstrating the important role of caspase-3 in the bserved cytotoxic effect. Taken together, these findings suggest that AECM-induced inhibition of human hepatocarcinoma cell proliferation is associated with the induction of apoptotic cell death via activation of caspase-3 and C. militaris may have therapeutic potential in human cancer.

NECROSIS OF ALVEOLAR BONE BY FORMOCRESOL : CASE REPORT (Formocresol에 의한 치조골 괴사의 치험례)

  • Park, Cheol-Hong;Lee, Chang-Seop;Lee, Sang-Ho;Lee, Nan-Young
    • Journal of the korean academy of Pediatric Dentistry
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    • v.32 no.4
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    • pp.657-661
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    • 2005
  • Various chemotherapeutic agents have been recommended for pulpotomy of primary teeth, and there are formocresol, ferric sulfate, and calcium hydroxide. Of those, formocresol has fixation effect of pulp tissue and high clinical success rate, so it is most commonly used agent. But formocresol has strong cytotoxic effects, thus many articles reported displacement and loss of permanent successor, amelogenesis imperfecta, mutation by general absorption, possibility of cancer induction. Recently, it has been reported that leakage by imperfect temporary sealing when FC-soaked cotton was inserted into the root canal caused necrosis of surrounding tissues. and that necrosis of alveolar bone related to the use of excessive formocresol. In this case, 2nd primary molar of upper left jaw was treated using formocresol in local clinic, but extracted because of lasting pain. Furthermore, symptoms didn't disappear so patient was refered to us. The patient was 8-year-old male, had foul odor from oral cavity and circular alveolar bone necrosis around the permanent successor' crown. Thus sequestrectomy was operated and observed through 19 months after operation, we found normal root development of permanent successor but no complete regeneration of alveolar bone defect and attached gingiva. Lesion of periodontal tissues by formocresol is irreversible, so we have to confirm the indication in using formocresol and pay attention to complete temporary sealing.

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Effects of Rhodiola Rosea on Brain Edema and Matrix Metalloproteinase Expressions Following Intracerebral Hemorrhage in the Rat (홍경천(紅景天)이 뇌조직내출혈(腦組織內出血) 흰쥐의 뇌부종(腦浮腫)과 Matrix Metalloproteinase 발현에 미치는 영향)

  • Ryu, Sa-Hyun;Lee, Joon-Suk;Shin, Jung-Won;Kim, Seong-Joon;Sohn, Nak-Won
    • The Korea Journal of Herbology
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    • v.26 no.4
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    • pp.169-180
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    • 2011
  • Objectives : This study aimed at evaluation of the effects of Rhodiola rosea on brain edema and expressions of matrix metalloproteinases (MMPs) related to blood-brain barrier (BBB) disruption. Methods : Brain edema following intracerebral hemorrhage (ICH) was induced by the stereotaxic intrastriatal injection of bacterial collagenase type VII in rats (Sprague-Dawley). Then ethanol extract of Rhodiola rosea was treated once a day for 3 days. Brain edema % and water contents, and BBB leakage were examined. Immunohistochemistry was processed for MMP-9, MMP-12, and iNOS expressions in the brain sections and each immuno-labeled cells were analyzed with image analysis software. Results : 1. Ethanol extract of Rhodiola rosea reduced brain edema following ICH in rats significantly. 2. Ethanol extract of Rhodiola rosea reduced excessive brain tissue water contents following ICH in rats significantly. 3. Ethanol extract of Rhodiola rosea reduced BBB leakage in the cerebral cortex following ICH in rats. 4. Ethanol extract of Rhodiola rosea reduced cellular edema of neurons in peri-hematoma and the cerebral cortex following ICH in rats significantly. 5. Ethanol extract of Rhodiola rosea reduced MMP-9 positive cells in the cerebral cortex following ICH in rats significantly. 6. Ethanol extract of Rhodiola rosea reduced MMP-12 positive vessels in the cerebral cortex following ICH in rats significantly. 7. Ethanol extract of Rhodiola rosea reduced iNOS positive cells in the cerebral cortex and external capsule following ICH in rats significantly. Conclusions : These results suggest that Rhodiola rosea reveals protective effect against brain edema and cytotoxic edema of neurons by means of down-regulation of MMPs and iNOS expressions, and inhibition of BBB leakage.

Anti-cancer Effects of Samultang-Gami on HeLa, HepG2, AGS Cells (사물탕가미방(四物湯加味方)의 항암효과에 대한 실험적 연구)

  • Jung, Jae-Joong;Goo, Sun-Young;Goo, Sun-Young;Sung, Jung-Suk;Kim, Dong-Il
    • The Journal of Korean Obstetrics and Gynecology
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    • v.23 no.3
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    • pp.38-55
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    • 2010
  • Purpose: This study was designed to find out the anti-cancer effects of Samultang-Gami which was composed of Rehmanniae Radix(RR), Angelicae Gigantis Radix(AGR), Cnidii Rhizoma(CR), Paeoniae Radix(PR), Cortex Moutan Radicis(CMR), Hedyotis Diffusa(HD) and Caesalpinia Sappan on HeLa, HepG2 and AGS cells. Methods: Various cancer cell lines including HeLa, HepG2 and AGS cells, were used. In vitro anti-cancer effects were measured by MTT assay using cancer cell lines treated with various concentrations of 70% ethanol extract of Samultang-Gami. Expression of cell cycle arrest mediators including Bax, Bcl-2, p53 and DARP-1 proteins were measured by Western blot analysis. Results: 1. Samultang-Gami decreased the viability of HeLa and HepG cells in a dosedependent manner. 2. AGR, CMR, PR and HD decreased the viability of HeLa, HepG2 and AGS cells. 3. We could observe that the decreased Bax and Bcl-2 expression level and the increased PARP-1 expression level by Samultang-Gami extracts treated in HeLa cells. 4. We could observe that the decreased Bcl-2 expression level and the increased Bax, p53 and PARP-1 expression level by RR extracts treated in HeLa cells. and also could observe that the reduction of the protein level of Bcl-2, p53 and PARP-1 and the increase of the protein level of Bax by PR in HeLa cells. 5. We could observe that the increased p53 expression level, the decreased PARP-1's that and the unchanged Bax and Bcl-2's that by Samultang-Gami extracts treated in HepG2 cells. 6. We could observe that the reduced Bcl-2 expression level by each of RR extracts and PR extracts in HepG2 cells. 7. The treatment of Samultang-Gami in AGS cells didn't have any effect on the expression level of Bax, Bcl-2, p53 and PARP-1. 8. We could observe that the increased p53 and PARP-1 expression level by each of CR, RR and PR extracts in AGS cells. Conclusion: Taken together, we suggest that Samultang-Gami exhibits cytotoxic effects on HeLa, HepG2 and AGS cells, causing apoptosis. The results showed that Samultang-Gami may do so by regulating the expression of specific target molecules that promote efficient apoptotic cell death in a dose-dependent manner.

Analysis of Differentially Expressed Genes by Sulindac Sulfide in Human Colorectal Cells (인간 대장암 세포주에서 sulindac sulfide 처리에 의해 차별적으로 발현되는 유전자 군의 분석)

  • Shin, Seung-Hwa;Kim, Jong-Sik
    • Journal of Life Science
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    • v.17 no.7 s.87
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    • pp.996-1001
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    • 2007
  • To investigate whether sulindac, sulindac sulfone, and sulindac sulfide could affect cancer cell viabilities, human colorectal HCTl16 cells were treated with 10 ${\mu}M$ of each NSAID. Among treated NSAms, sulindac sulfide dramatically decreased the cell viabilities detected by MTS and the cytotoxic effect showed dose-dependent manner. To understand the molecular mechanism of cell death in response to sulindac sulfide treatment, we performed oligo DNA microarray analysis. We found that 23 genes were up-regulated more than 2 folds, whereas 33 genes were down-regulated more than 2 folds by treatment of 10 ${\mu}M$ sulindac sulfide. Among the up-regulated genes, we selected 3 genes (NAG-1, DDIT3, PCK2) and performed RT-PCR and quantitative real-time PCR to cofirm microarray data. The results of RT-PCR and real-time PCR were highly accorded with those of microarray experiment. As NAG-1 is well-known gene as tumor suppressor, we detected changes of NAG-1 expression by 10 ${\mu}M$ of sulindac, sulindac sulfone, and sulindac sulfide. The results of RT-PCR and quantitacve real-time PCR indicated that sulindac sulfide was the strongest inducer of NAG-1 among treated NSAIDS. This result implies that induction of NAG-1 by sulindac sulfide plays important role in cell death of colorectal cancer. Overall, we speculate that these results may be helpful in understanding the molecular mechanism of the cancer chemoprevention by sulindac sulfide in human colorectal cancer.

Physiological Effect of Korean Black Soybean Pigment (한국산 검정콩 색소의 생리활성효과)

  • Son, Jun-Ho;Choung, Myoung-Gun;Choi, Hee-Jin;Jang, Un-Bin;Son, Gyu-Mok;Byun, Myung-Woo;Choi, Cheong
    • Korean Journal of Food Science and Technology
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    • v.33 no.6
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    • pp.764-768
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    • 2001
  • Physiological effects of Korean black soybean pigment were investigated. Major anthocyanin pigments of Korean black soybean were extracted with 1% HCl for 24 hours at $4^{\circ}C$. Inhibitory effects of angiotensin converting enzyme ($IC_{50}$) were 0.22 mg/mL (Kumjungkong #1), 0.28 mg/mL (Ilpumkumjungkong) and 0.38 mg/mL (Milyang #95). Inhibitory effects xanthine oxidase ($IC_{50}$) were 0.118 mg/mL (Kumjungkong #1), 0.165 mg/mL (Ilpumkumjungkong) and 0.163 mg/mL (Milyang #95). The cPLA2 inhibitory effects ($IC_{50}$) were $19.7\;{\mu}g/mL$, $10.7\;{\mu}g/mL$ and $25.3\;{\mu}g/mL$. The cytotoxic effects of anthocyanins from Milyang #95 were 66.0% against human colon cell line (HT29), 58.2% against human liver cell line (HepG2) and 64.4% against mouse liver cell line (Hepa), respectively.

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Utilization of [6]-gingerol as an origin discriminant marker influencing melanin inhibitory activity relative to its content in Pinellia ternata (반하(Pinellia ternata)에서의 [6]-gingerol 함량과 멜라닌 저해 활성에 영향을 미치는 원산지 판별 마커로의 활용)

  • An, Ju Hyeon;Won, Hyo Jun;Seo, Soo-Kyung;Kim, Doo-Young;Ku, Chang-Sub;Oh, Sei-Ryang;Ryu, Hyung Won
    • Journal of Applied Biological Chemistry
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    • v.59 no.4
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    • pp.323-330
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    • 2016
  • Pinellia ternata Breitenbach, the natural medicinal plant of the Araceae family, is a perennial plant originated from the East Asia, but also widely distributed in Europe and North America. Its tuber is used as traditional medicine for treatment of various diseases such as vomiting, inflammation, and traumatic injury. Pharmacological studies revealed that P. ternata possesses anticonvulsant, anti-tumor, insecticidal, and cytotoxic activities. Despite being well-known as the useful medicinal plant, there is no reliable, standardized method for origin discrimination. Ultra performance liquid chromatography-photodiode array detector and quadrupole time of flight-mass spectrometry based metabolite-profiling was applied to explore significant metabolite for origin discrimination between Korean and Chinese P. ternata. One compound was isolated from Korean P. ternata using repeated ODS column chromatography by bioactivity guided fractionation, and determined as [6]-gingerol according to the results of spectroscopic data including nuclear magnetic resonance and MS. This compound was selected as cosmeceutical biomarker by fingerprints, and it was associated to melanin inhibitory effect determining its origin authenticity. Furthermore, the calibration curve of biomarker was prepared using validated method for the comparison of content between Korean and Chinese P. ternata. This is the report to address the selection and successful validation of the discriminant metabolite for confirmation of Korean P. ternata.

Siamese Crocodile White Blood Cell Extract Inhibits Cell Proliferation and Promotes Autophagy in Multiple Cancer Cell Lines

  • Phosri, Santi;Jangpromma, Nisachon;Chang, Leng Chee;Tan, Ghee T.;Wongwiwatthananukit, Supakit;Maijaroen, Surachai;Anwised, Preeyanan;Payoungkiattikun, Wisarut;Klaynongsruang, Sompong
    • Journal of Microbiology and Biotechnology
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    • v.28 no.6
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    • pp.1007-1021
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    • 2018
  • Cancer represents one of the most significant threats to human health on a global scale. Hence, the development of effective cancer prevention strategies, as well as the discovery of novel therapeutic agents against cancer, is urgently required. In light of this challenge, this research aimed to evaluate the effects of several potent bioactive peptides and proteins contained in crocodile white blood cell extract (cWBC) against LU-1, LNCaP, PC-3, MCF-7, and CaCo-2 cancer cell lines. The results demonstrate that 25, 50, 100, and $200{\mu}g/ml$ cWBC exhibits a strong cytotoxic effect against all investigated cell lines ($IC_{50}$ $70.34-101.0{\mu}g/ml$), while showing no signs of cytotoxicity towards noncancerous Vero and HaCaT cells. Specifically, cWBC treatment caused a significant reduction in the cancerous cells' colony forming ability. A remarkable suppression of cancerous cell migration was observed after treatment with cWBC, indicating potent antimetastatic properties. The mechanism involved in the cancer cell cytotoxicity of cWBC may be related to apoptosis induction, as evidenced by typical apoptotic morphology features. Moreover, certain cWBC concentrations induced significant overproduction of ROS and significantly inhibited the $S-G_2/M$ transition in the cancer cell. The molecular mechanisms of cWBC in apoptosis induction were to decrease Bcl-2 and XIAP expression levels and increase the expression levels of caspase-3, caspase-8, and p53. These led to a decrease in the expression level of the cell cycle-associated gene cyclin-B1 and the arrest of cell population growth. Consequently, these findings demonstrate the prospect of the use of cWBC for cancer therapy.

Quantification of 4-Hydroxyalkenals in Oils Consumed in Korea (상용하는 식물성 기름에서 지질과산화의 독성물질 4-hydroxy-2-alkenals 정량)

  • Surh, Jeong-Hee;Kwon, Hoon-Jeong
    • Korean Journal of Food Science and Technology
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    • v.34 no.5
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    • pp.905-910
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    • 2002
  • 4-Hydroxyalkenals are cytotoxic aldehydes generated by the oxidation of n-6 and n-3 polyunsaturated fatty acids. To evaluate the potential risk of 4-hydroxyalkenals on Koreans, quantitative data of various oils are necessary. Simultaneous monitoring of 4-hydroxyhexenal and 4-hydroxynoneal in 39 samples including new and used ones through single ion monitoring mode of GC/MS detected both aldehydes in all samples tested, ranging from 0.21 to 26.9 nmol/g for 4-hydroxy-2-hexenal and 0.06 to 56.6 nmol/g for 4-hydroxy-2-nonenal. Frying oils collected from local markets showed 2.28-7.90 and 8.31-30.5 nmol/g of 4-hydroxyhexenal and 4-hydroxynoneal, respectively. National health and nutrition survey data were employed to determine the exposure effect to these 4-hydroxyalkenals from the four most consumed oils in Korea. Daily exposures to hydroxyalkenals excluding possible exposure from fried food were $1.9\;{\mu}g$ from soybean oil, $0.5\;{\mu}g$ from sesame oil, $0.2\;{\mu}g$ from corn oil, and $0.1\;{\mu}g$ from perilla oil. Due to the increasing consumption of polyunsaturated fatty acids in Korea, these data may provide valuable information for evaluating possible physiological effects of 4-hydroxyalkenals from vegetable oils.