• Title/Summary/Keyword: Hepatocarcinoma

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Cytotoxic and Apoptotic Effects of Saponins from Akebia quinata on HepG2 Hepatocarcinoma Cells (으름유래 사포닌의 HepG2 간암세포에 대한 세포독성 및 세포자살유도 효과)

  • Kang, Hye-Sook;Kang, Jae-Seon;Jeong, Woo-Sik
    • Food Science and Preservation
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    • v.17 no.3
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    • pp.311-319
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    • 2010
  • Four saponins (1~4) were isolated from Akebia quinata pericarp through bioassay-guided fractionation. Pericarps of A. quinata were extracted with ethanol and sequentially fractionated with dichloromethane, ethyl acetate, butanol and water. Compounds 1~4 from the butanol fraction were identified as 3-O-${\alpha}$-L-arabinopyranosyl hederagenin (${\delta}$-hederin), 3-O-${\alpha}$-L-rhamnopyranosyl (1${\rightarrow}$2) ${\alpha}$-L-arabinopyranoly oleanolic acid (${\beta}$-hederin), 3-O-${\beta}$-D-xylopyranosyl (1${\rightarrow}$3) ${\alpha}$-L-arabinopyranosyl hederagenin (saponin C), and 3-O ${\alpha}$-L-rhamnopyranosyl (1${\rightarrow}$2) ${\alpha}$-L-arabinopyranosyl hederagenin (${\alpha}$-hederin) based on the spectroscopic evidences, respectively. Oleanolic acid and hederagenin were identified as the corresponding sapogenins by acid-hydrolysis. These compounds exhibited strong cytotoxic activity in MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxy-methoxyphenyl)-2-(4-sulfophenyl)-2H- tetrazolium, inner salt] assay on HepG2 cells. ${\beta}$-Hederin obviously attenuated the expression of bcl-2, an anti-apoptotic protein. All of the compounds also induced the activity of caspase-3, an apoptotic enzyme, while ${\alpha}$-hederin was the most potent activator of the enzyme. Our data demonstrate for the first time the apoptosis-inducing activity of A. quinata. These results suggest that A. quinata could be used as a potential source of natural cancer chemopreventive agents.

Immune Activities in Hypericum perforatum L. (고추나물의 면역 활성)

  • Park, Jin-Hong;Kim, Dae-Ho;Choi, Geun-Pyo;Ryu, Lee-Ha;Lee, Kang-Yoon;Lee, Hyeon-Yong
    • Korean Journal of Medicinal Crop Science
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    • v.12 no.4
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    • pp.304-308
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    • 2004
  • Immune enhancing activities of water and ethanol extracts of Hypericum perforatum L. (HP) were examined. HP extracts inhibited the growth of human hepatocarcinoma, human gastric cancer cell and human breast cancer cells in concentration-dependent mammers over a concentration range of $0.05{\sim}1.0\;mg/ml$, showing inhibiton of more than 80% with the concentration of 1.0 mg/ml. However, HP the same concentration. Overall selectivity of the extracts on the three human cancer lines was over 3.5, which is higher than those from the conventional herbs. The growth of human immune B and T cells was enhanced up to 1.4 to 2.0 folds by the addition of the extracts for 4 days, compared to controls. Ethanol extracts of HP after 6 days incubation increased the secretions of tumor necrosis factor-alpha $(TNF-{\alpha})$ from T cells and interleukin-6 (IL-6) from B cells to 6.7 pg/cell and 6.8 pg/cell, respectively. These results suggest that HP has a potent immune enhancing effect.

Cytotoxicity of Extracts and Fractions from Echinacea pupurea L. on Human Cancer Cells (Echinacea purpurea L. 추출물 및 분획물의 암세포 독성)

  • Park, Jin-Hong;Lee, Mi-Kyoung;Mun, Hyung-Chul;Choi, Geun-Pyo;Lee, Seo-Ho;Lee, Hyeon-Soo;Ryu, Lee-Ha;Lee, Gang-Yoon;Lee, Hyeon-Yong
    • Korean Journal of Medicinal Crop Science
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    • v.12 no.4
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    • pp.309-314
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    • 2004
  • The cytotoxic effects of water and ethanol extracts of Echinacea purpurea (L.) (EP) and chloroform, ethyl acetate, butanol and aqueous fractions from each extract of EP were examined. Every extract and fraction of EP inhibited the growth of human hepatocarcinoma, human gastric cancer cell, human breast cancer cells and human lung carcunoma in concentration-dependent manners over a concentration range of $0.05{\sim}1.0\;mg/ml$. Most extracts and fractions with the concentraction of 1 mg/ml showed strong inhibition of more than 70% for every cancer cell. Only aqueous fractions of each extract showed very weak inhibitons of 12 to 25% on the growth of human normal lung cell with the concentration of 1 mg/ml. Overall selectivity of the extrats and fractions on the four human cancer cell lines was over 2.5. These results indicate that EP has a very potent selective toxicity for cancer cells.

Improvement of Anticancer Activation of Ultrasonificated Extracts from Acanthopanax senticosus Harms, Ephedra sinica Stapf, Rubus coreanus Miq. and Artemisia capillaris Thunb (초음파 병행 추출을 이용한 가시오갈피, 마황, 복분자 및 인진쑥의 항암활성 증진)

  • Park, Jin-Hong;Lee, Hyun-Soo;Mun, Hyoung-Chul;Kim, Dae-Ho;Seong, Nak-Sul;Jung, Hae- Gon;Bang, Jin-Ki;Lee, Hyeon-Yong
    • Korean Journal of Medicinal Crop Science
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    • v.12 no.4
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    • pp.273-278
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    • 2004
  • The anticancer activities of the extracts from Acanthopanax senticosus Harms, Ephedra sinica Stapf, Rubus coreanus Miq and Artemisia capillaris Thunb were compared according to extract systems. About 70% of the growth of human hepatocarcinoma cancer cell was inhibited in adding 1.0 mg/ml of the water extract from Rubus coreanus Miq with ultrasonification at $60^{\circ}C$. The growth of human normal lung cell was limited to 25% in adding the extracts with ultrasonification at $60^{\circ}C$. The effect of extracts obtained by only water and with ultrasonification on different of human promyelocytic leukemia cells was also observed.

Active hexose correlated compound potentiates the antitumor effects of low-dose 5-fluorouracil through modulation of immune function in hepatoma 22 tumor-bearing mice

  • Cao, Zhiyun;Chen, Xuzheng;Lan, Lan;Zhang, Zhideng;Du, Jian;Liao, Lianming
    • Nutrition Research and Practice
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    • v.9 no.2
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    • pp.129-136
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    • 2015
  • BACKGROUND/OBJECTIVES: A variety of immunomodulators can improve the efficacy of low-dose chemotherapeutics. Active hexose correlated compound (AHCC), a mushroom mycelia extract, has been shown to be a strong immunomodulator. Whether AHCC could enhance the antitumor effect of low-dose 5-fluorouracil (5-FU) via regulation of host immunity is unknown. MATERIALS/METHODS: In the current study Hepatoma 22 (H22) tumor-bearing mice were treated with PBS, 5-FU ($10mg{\cdot}kg^{-1}{\cdot}d^{-1}$, i.p), or AHCC ($360mg{\cdot}kg^{-1}{\cdot}d^{-1}$, i.g) plus 5-FU, respectively, for 5 d. $CD^{3+}$, $CD^{4+}$, $CD^{8+}$, and NK in peripheral blood were detected by flow cytometry. ALT, AST, BUN, and Cr levels were measured by biochemical assay. IL-2 and $TNF{\alpha}$ in serum were measured using the RIA kit and apoptosis of tumor was detected by TUNEL staining. Bax, Bcl-2, and TS protein levels were measured by immunohistochemical staining and mRNA level was evaluated by RT-PCR. RESULTS: Diet consumption and body weight showed that AHCC had no apparent toxicity. AHCC could reverse liver injury and myelosuppression induced by 5-FU (P < 0.05). Compared to mice treated with 5-FU, mice treated with AHCC plus 5-FU had higher thymus index, percentages of $CD^{3+}$, $CD^{4+}$, and NK cells (P < 0.01), and ratio of $CD^{4+}$/$CD^{8+}$ (P < 0.01) in peripheral blood. Radioimmunoassay showed that mice treated with AHCC plus 5-FU had the highest serum levels of IL-2 and $TNF{\alpha}$ compared with the vehicle group and 5-FU group. More importantly, the combination of AHCC and 5-FU produced a more potent antitumor effect (P < 0.05) and caused more severe apoptosis in tumor tissue (P < 0.05) compared with the 5-FU group. In addition, the combination of AHCC and 5-FU further up-regulated the expression of Bcl-2 associated X protein (Bax) (P < 0.01), while it down-regulated the expression of B cell lymphoma 2 (Bcl-2) (P < 0.01). CONCLUSIONS: These results support the claim that AHCC might be beneficial for cancer patients receiving chemotherapy.

Ethanol but not Aqueous Extracts of Tubers of Sauromatum Giganteum(Engl.) Cusimano and Hett Inhibit Cancer Cell Proliferation

  • Gao, Shi-Yong;Li, Jun;Wang, Long;Sun, Qiu-Jia;Gong, Yun-Fei;Gang, Jian;Su, Yi-Jun;Ji, Yu-Bin
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.24
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    • pp.10613-10619
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    • 2015
  • Background: Both alcohol and aqueous extracts of Sauromatum giganteum(Engl.) Cusimano and Hett, the dried root tuber of which is named Baifuzi in Chinese, have been used for folklore treatment of cancer in Northeast of China. However, little is known about which is most suitable to the cancer therapy. Materials and Methods: Serum pharmacology and MTT assays were adopted to detect the effects of ethanol and aqueous extracts of Sauromatum giganteum(Engl.) Cusimano and Hett, prepared by heat reflux methods, on proliferation of different cancer cells. Results: Cancer cells treated with medium supplemented with 10%, 20%, 40% serum(v/v) containing ethanol extract had a decline in viability, with inhibition rates of 7.69%, 21.8%, 41.9% in MCF-7 cells, 42.8%, 48.1%, 51.8% in SGC-7901 cells, 44.1%, 49.2%, 53.7% in SMMC-7721 cells, 6.8%, 15.2%, 39.8% in HepG2 cells, 7.57%, 16.3%, 36.2% in HeLa cells, 6.24%, 12.5%, 27.4% in A549 cells, and 7.20%, 17.5%, 31.3% in MDA-MB-231 cells, respectively. Viability in the aqueous extract groups was no different with that of controls. Conclusions: An ethanol extract of Sauromatum giganteum(Engl.) Cusimano and Hett inhibited the proliferation of SMMC-7721, SGC-7901 and MCF-7 cells, which supports the use of alcoholic but not aqueous extracts for control of sensive cancers, which might include hepatocarcinoma, gastric cancer and breast cancer.

The Effect of the Bujeonghangam-tang Extract on Hepatocellular Carcinogenesis and Hepatic Cirrhosis Induced by Diethylnitrosarnine and CCl4 in Rats (부정항암탕(扶正抗癌湯) 추출액이 Diethylnitrosamine과 CCl4로 유발된 흰쥐의 간암 형성 및 간경화에 미치는 영향)

  • Moon, Young-Ho;Won, Jin-Hee;Moon, Goo;Heo, Rae-Kyong;Seung, Kee-Moon;Lee, In-Young;Jang, Myung-Joon;Kwon, So-Yeon;Yu, Deok-Seon
    • Journal of Pharmacopuncture
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    • v.13 no.2
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    • pp.13-31
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    • 2010
  • Objective : Bujeonghangam-tang(BH) has been used for cure of tumor as a traditional medicine. This study was carried out to clarify the effect of BH extract on hepatocellular carcinogenesis and hepatic cirrhosis induced by Diethylnitrosamine(DENA) and $CCl_4$ in Rats. Method : Experimental groups were divided into two, 8th and 12th week groups, and subdivided into four; normal group(Nor), cirrhosis and hepatic cancer inducing control group(Con), and BH extract 320 mg/kg/day(BHA) or 640 mg/kg/day(BHB) administered groups to Con. Results: In the 8th week group: The body weight decreased significantly in Con compared with the Nor. The activities of transaminase, alkaline phosphatase(ALP), and lactacte dehydrogenase(LDH) were significantly increased(p<0.05) in the Con compared with Nor, but decreased in the BHA and BHB compared with Con. Alpha fetoprotein(AFP) were the most increased in the Con compared to BHA and BHB. The results of light microscopical observation, a number of hepatocytes were damaged in the Con compared with Nor and BH extract administerd groups. The number of hepatic p53 positive cells was reduced in the BH extract administered groups. According to the electron microscopical observation, hepatocarcinoma cells were observed distinctly in the Con compared with BH extract administered groups. In the 12 weeks group: The results of body were similar to 8th week groups. The activities of transaminase and ALT were significantly increased(p<0.05) in the Con compared with Nor. LDH was significantly(p<0.05) increased in the Con compared with Nor but significantly (p<0.05) decreased in the BHB. Alpha fetoprotein(AFP) were the most increased in the Con among ex perimental groups. The activities of superoxide dismutase(SOD) were significantly (p<0.05) increased in the Con, but the activities of catalase were not increased(p<0.05) compared with Nor. The number of hepatic p53 positive cells was increased in the Con. The results of electron microscopical observation were similar to 8th week groups. Conclusion : These results suggest that ad ministration of BH extract suppress or retard DENA and $CCl_4$-induced hepatocellular carcinogenesis and hepatic cirrhosis in rats.

Enhanced Immune Activity and Cytotoxicity of Artemisia capillaris Thunb. Extracts against Human Cell Lines (사철쑥 추출물의 면역세포의 생육증진 및 세포독성)

  • Lee, Mi-Kyoung;Choi, Geun-Pyo;Ryu, Lee-Ha;Lee, Gang-Yoon;Yu, Chang-Yeon;Lee, Hyeon-Yong
    • Korean Journal of Medicinal Crop Science
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    • v.12 no.1
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    • pp.36-42
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    • 2004
  • The immune activation and anticancer activities of the water and ethanol extracts from Artemisia capillaris Thunb. were studied. The growth of human hepatocarcinoma and human gastric cancer cell was inhibited by the addition of $1.0\;mg/m{\ell}$ of the water extract, by about 77% and 95%, respectively. The growth of human breast cancer cells was also inhibited by addition of $0.5\;mg/m{\ell}$ of both water and ethanol extracts by 88%. The growth of human normal lung cell, HEL299 was inhibited by 15% indicating very low cytotoxicity of both extracts. Overall selectivity of the both extracts on several human cancer cell line was over 2.5. The growth of both human B and T cells was enhanced up to 1.6 to 2.1 times by adding the ethanol extracts. The secretion of cytokines, $TNF-{\alpha}$ and IL-6, from human B cells was also increased showing $68\;pg/m{\ell}$ and $67\;pg/m{\ell}$, respectively, compared to $35{\sim}40\;pg/m{\ell}$ of the control. In terms of the immune activity, there was not much difference between water and ethanol extracts of Artemisia capillaris Thunb. It implies that the extraction solvent could not differ the biological activities of the extracts. Based on these results, Artemisia capillaris Thunb. can be developed into a potentially useful cancer chemoprentive agent.

Enhancement of TRAIL-Mediated Apoptosis by Genistein in Human Hepatocellular Carcinoma Hep3B Cells: Roles of p38 MAPK Signaling Pathway (인체간암세포에서 genistein의 TRAIL에 의한 apoptosis 유도 상승효과에서 미치는 p38 MAPK signaling pathway의 영향)

  • Jin, Cheng-Yun;Park, Cheol;Park, Sang-Eun;Hong, Sang-Hoon;Choi, Yung-Hyun
    • Journal of Life Science
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    • v.21 no.11
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    • pp.1549-1557
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    • 2011
  • Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can selectively induce apoptosis in many types of transformed cells; however, some human hepatocellular carcinoma cells are particularly resistant to the effects of TRAIL. Although genistein, a natural isoflavonoid phytoestrogen, has been shown to have pro-apoptotic activity against human cancer cell lines, little is known about the mechanism of genistein in terms of TRAIL-induced apoptosis. In the present study, it was investigated whether or not combined treatment with genistein and TRAIL synergistically induced apoptosis in Hep3B hepatocarcinoma cells. Results indicate that treatment with TRAIL in combination with nontoxic concentrations of genistein sensitized TRAIL-resistant Hep3B cells to TRAIL-induced apoptosis, which was associated with mitochondrial dysfunction. Further, the inhibition of p38 mitogen-activated protein kinase (MAPK) activation markedly decreased genistein and TRAIL-induced cell viability and apoptosis by enhanced truncation of Bid, increase of pro-apoptotic Bax, decrease of anti-apoptotic Bcl-2, and release of cytochrome c from mitochondria to cytoplasm. Activation of caspases and degradation of poly (ADP-ribose) polymerase induced by the combined treatment was also markedly increased by the inhibition of p38 MAPK, through the mitochondrial amplification step. In conclusion, our data suggest that genistein sensitizes TRAIL-induced-apoptosis via p38 MAPK-dependent pathway.

Modulation of Cell Cycle Regulators by Sulforaphane in Human Mepatocarcinoma HepG2 Cells (HepG2 인체간암세포의 세포주기조절인자 발현에 미치는 sulforaphane의 영향)

  • Bae, Song-Ja;Kim, Gi-Young;Yoo, Young-Hyun;Choi, Byung-Tae;Choi, Yung-Hyun
    • Journal of Life Science
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    • v.16 no.7 s.80
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    • pp.1235-1242
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    • 2006
  • Sulforaphane, an isothiocyanate derived from hydrolysis of glucoraphanin in broccoli and other cruciferous vegetables, was shown to induce phase II detoxification enzymes and inhibit chemically induced mammary tumors in rodents. Recently, sulforaphane is known to induce cell cycle arrest and apoptosis in human canter cells, however its molecular mechanisms are poorly understood. In tile present study, we demonstrated that sulforaphane acted to inhibit proliferation and induce morphological changes of human hepatocarcinoma HepG2 cells. Treatment of HepG2 cells with $10{\mu}M\;or\;15{\mu}M$ sulforaphane resulted in significant G2/M cell cycle arrest as determined by DNA flow cytometry. Moreover, $20{\mu}M$ sulforaphane significantly induced the population of sub-G1 cells suggesting that sulforaphane induced apoptosis. This anti-proliferative effect of sulforaphane was accompanied by a marked inhibition of ryclin A, cyclin 31 and Cdc2 protein. However, the levels of tumor suppressor p53 and Cdk inhibitor p21 mRNA and protein expression were significantly increased by sulforaphane treatment in a concentration-dependent manner. Although further studies are needed, the present work suggests that sulforaphane may be a potential rhemoprevetiveichemotherapeucc agent for the treatment of human cancer cells.