• Title/Summary/Keyword: growth inhibitory effects

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Cell Cycle Modulation of MCF-7 and MDA-MB-231 by a Sub-Fraction of Strobilanthes crispus and its Combination with Tamoxifen

  • Yaacob, Nik Soriani;Kamal, Nik Nursyazni Nik Mohamed;Wong, Kah Keng;Norazmi, Mohd Nor
    • Asian Pacific Journal of Cancer Prevention
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    • 제16권18호
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    • pp.8135-8140
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    • 2016
  • Background: Cell cycle regulatory proteins are suitable targets for cancer therapeutic development since genetic alterations in many cancers also affect the functions of these molecules. Strobilanthes crispus (S. crispus) is traditionally known for its potential benefits in treating various ailments. We recently reported that an active sub-fraction of S. crispus leaves (SCS) caused caspase-dependent apoptosis of human breast cancer MCF-7 and MDA-MB-231 cells. Materials and Methods: Considering the ability of SCS to also promote the activity of the antiestrogen, tamoxifen, we further examined the effect of SCS in modulating cell cycle progression and related proteins in MCF-7 and MDA-MB-231 cells alone and in combination with tamoxifen. Expression of cell cycle-related transcripts was analysed based on a previous microarray dataset. Results: SCS significantly caused G1 arrest of both types of cells, similar to tamoxifen and this was associated with modulation of cyclin D1, p21 and p53. In combination with tamoxifen, the anticancer effects involved downregulation of $ER{\alpha}$ protein in MCF-7 cells but appeared independent of an ER-mediated mechanism in MDA-MB-231 cells. Microarray data analysis confirmed the clinical relevance of the proteins studied. Conclusions: The current data suggest that SCS growth inhibitory effects are similar to that of the antiestrogen, tamoxifen, further supporting the previously demonstrated cytotoxic and apoptotic actions of both agents.

Suppression of Human Prostate Cancer Cell Growth by β-Lapachone via Down-regulation of pRB Phosphorylation and Induction of Cdk Inhibitor p21WAF1/CIP1

  • Choi, Yung-Hyun;Kang, Ho-Sung;Yoo, Mi-Ae
    • BMB Reports
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    • 제36권2호
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    • pp.223-229
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    • 2003
  • The product of a tree (Tabebuia avellanedae) from South America, $\beta$-lapachone, is known to exhibit various pharmacological properties, the mechanisms of which are poorly understood. The aim of the present study was to further elucidate the possible mechanisms by which $\beta$-lapachone exerts its anti-proliferative action in cultured human prostate cancer cells. We observed that the proliferation-inhibitory effect of $\beta$-lapachone was due to the induction of apoptosis, which was confirmed by observing the morphological changes and cleavage of the poly(ADP-ribose) polymerase protein. A DNA flow cytometric analysis also revealed that $\beta$-lapachone arrested the cell cycle progression at the G1 phase. The effects were associated with the down-regulation of the phosphorylation of the retinoblastoma protein (pRB) as well as the enhanced binding of pRB and the transcription factor E2F-1. Also, $\beta$-lapachone suppressed the cyclindependent kinases (Cdks) and cyclin E-associated kinase activity without changing their expressions. Furthermore, this compound induced the levels of the Cdk inhibitor $p21^{WAF1/CIP1}$ expression in a p53-independent manner, and the p21 proteins that were induced by $\beta$-lapachone were associated with Cdk2. $\beta$-lapachone also activated the reporter construct of a p21 promoter. Overall, our results demonstrate a combined mechanism that involves the inhibition of pRB phosphorylation and induction of p21 as targets for $\beta$-lapachone. This may explain some of its anticancer effects.

지황(地黃)과 발효(醱酵) 지황(地黃)의 생리활성 비교 연구 (Comparison of Biological Activities on Rehmanniae Radix and Fermented Rehmanniae Radix)

  • 김은혜;김경신;채순기;김병수;강정수
    • 동의생리병리학회지
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    • 제26권3호
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    • pp.306-313
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    • 2012
  • Herbal medicines are medicinal products containing a single or a mixture of two or more different herbal substances or herbal preparations as active principles. Recently, much attention has been paid to developing various kinds of fermented herbal extracts, a new type of traditional herbal medicine in the field of Korean traditional medicine. The fermentation of medicinal herbs is intended to exert a favorable influence on bioestability, bioavaliablilty and pharmacological activity of herbal extract in the gastrointestinal tract as well as intensifying the nutritional and pharmacological aspects of the medicinal herbs. The purpose of this study was to investigate biological activities of fermented Rehmanniae Radix by lactic acid bacteria at $30^{\circ}C$ for 3 days in comparison with those for Rehmanniae Radix The fermented Rehmanniae Radix exhibited different chemical profile to Rehmanniae Radix generated with HPLC, indicating production of new ingredients during fermentation. Rehmanniae Radix served as good nutritional sources for the growth of lactic acid bacteria showing increased number of bacteria during fermentation. Toxic effect of the fermented Rehmanniae Radix to cells were not seen judged by the MTT assay. The fermented Rehmanniae Radix exhibited better antioxidant effect than non-fermented Rehmanniae Radix analyzed by a SOD-likely assay. Both hypoglycemic and hypotensive effects of the fermented Rehmanniae Radix were also detected and better than those for Rehmanniae Radix in showing dose-dependent inhibitory effects on alpha-glucosidase and ACE, respectively. In conclusion, fermented Rehmanniae Radix appears to have more biological activities than non-feremented Rehmanniae Radix showing not only antioxidant effect but also cardiovascular protection.

창부육군탕(蒼附六君湯)이 Estradiol Valerate로 유도된 흰쥐의 다낭성 난소에 미치는 영향 (Effects of Changbuyeukgun-Tang on the Estradiol Valerate-induced Polycystic Ovaries in Rats)

  • 김희주;김윤상;임은미
    • 대한한방부인과학회지
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    • 제21권2호
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    • pp.1-16
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    • 2008
  • Purpose: In this rearch, we made a plan to investigate the effects of Changbuyeukgun-Tang(CET) on the polycystic ovary(PCOS) induced by estradiol valerate(EV) in rats. PCO was induced by single intramuscular injection with EV(4㎎) in female rats. Rats(n=8) in normal group were injected with sesame oil and orally administrated distilled water for 8weeks Rats in PCO control group(n=8) were injected with EV and orally administrated distilled water for 8weeks. Rats in CET treated group(n=8) were injected with EV and orally administrated CET for 8weeks. Methods: We measured the weights of the body, the ovary, the uterus and the adrenal gland. And also, we analyzed ovarian histopathology, NGF and CRF immunohistochemistry. Results: The results were as follows1. the weights(㎎) of the ovaries in CET treated group were significantly increased(p<0.001) compared with PCO control group. 2. the number of the mature follicles in CET treated group were significantly increased(p<0.01) compared with PCO control. 3. the number of the atresia follicles in CET treated group were significantly decreased(p<0.01) compared with PCO control. 4. the number of the corpora in CET treated group were significantly increased(p<0.05) compared with PCO control. 5. the expressions of NGF-immunoreactive cells in the ovarian granulosa cells of rats in CET treated group were less observed than PCO control group. Conclusion: According to these results, we finally concluded that Changbuyeukgun-Tang(CET) has the inhibitory effect on the development of EV-induced polycystic ovary. And we deduced that the effect of it may be related to the decreased NGF activities in the ovary.

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Inhibitory Effects of α-Pinene on Hepatoma Carcinoma Cell Proliferation

  • Chen, Wei-Qiang;Xu, Bin;Mao, Jian-Wen;Wei, Feng-Xiang;Li, Ming;Liu, Tao;Jin, Xiao-Bao;Zhang, Li-Rong
    • Asian Pacific Journal of Cancer Prevention
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    • 제15권7호
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    • pp.3293-3297
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    • 2014
  • Background: Pine needle oil from crude extract of pine needles has anti-tumor effects, but the effective component is not known. Methods: In the present study, compounds from a steam distillation extract of pine needles were isolated and characterized. Alpha-pinene was identified as an active anti-proliferative compound on hepatoma carcinoma BEL-7402 cells using the MTT assay. Results: Further experiments showed that ${\alpha}$-pinene inhibited BEL-7402 cells by arresting cell growth in the G2/M phase of the cell cycle, downregulating Cdc25C mRNA and protein expression, and reducing cycle dependence on kinase 1(CDK1) activity. Conclusion: Taken together, these findings indicate that ${\alpha}$-pinene may be useful as a potential anti-tumor drug.

Mechanisms of Hela Cell Apoptosis Induced by Abnormal Savda Munziq Total Phenolics Combined with Chemotherapeutic Agents

  • Zhang, Yun-Xia;Abliz, Guzalnur;Ye, Wei-Jun;Mutalipu, Zuohelaguli;Li, Xiao-Wen;Wang, Hai-Qin;Buranjiang, Gulimire;Upur, Halmurat
    • Asian Pacific Journal of Cancer Prevention
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    • 제15권2호
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    • pp.743-747
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    • 2014
  • Objective: To investigate the effects of abnormal Savda Munziq (ASMq) total phenolics combined with cisplatin and docetaxel on the Hela cell growth. Methods: In vivo cultured Hela cells were treated with cisplatin, docetaxel, total phenolics, cisplatin+total phenolics or docetaxel+total phenolics. MTT was performed to assess inhibition of cell proliferation, flow cytometry to detect apoptosis, and semi-quantitative RT-PCR to test for survivin and Bcl-2 expression. Results: The total phenolics, cisplatin and docetaxel had significant inhibitory and apoptosis-promoting effects on Hela cells (P<0.05), with the early apoptotic rates of $12.8{\pm}0.70%$, $18.9{\pm}3.79%$ and $15.8{\pm}3.8%$; the total phenolics, cisplatin and docetaxel significantly decreased the expression of Bcl-2 and survivin (all P<0.01), especially when used in combination. Conclusion: ASMq total phenolics, combined with cisplatin and docetaxel, could promote the apoptosis of Hela cells possibly through reducing the expression of Bcl-2 and survivin.

Steroidal Saponins from Paris polyphylla Suppress Adhesion, Migration and Invasion of Human Lung Cancer A549 Cells Via Down-Regulating MMP-2 and MMP-9

  • He, Hao;Zheng, Lei;Sun, Yan-Ping;Zhang, Guang-Wei;Yue, Zheng-Gang
    • Asian Pacific Journal of Cancer Prevention
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    • 제15권24호
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    • pp.10911-10916
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    • 2015
  • Background: Tumor metastases are the main reasons for oncotherapy failure. Paris polyphylla (Chinese name: Chonglou) has traditionally been used for its anti-cancer actions. In this article, we focus on the regulation of human lung cancer A549 cell metastases and invasion by Paris polyphylla steroidal saponins (PPSS). Materials and Methods: Cell viability was evaluated in A549 cells by MTT assay. Effects of PPSS on invasion and migration were investigated by wound-healing and matrigel invasion chamber assays. Adhesion to type IV collagen and laminin was evaluated by MTT assay. Expression and protease activity of two matrix metalloproteinases (MMPs), MMP-2 and MMP-9, were analyzed by Western blotting and gelatin zymography, respectively. Results: PPSS exerted growth inhibitory effects on A549 cells, and effectively inhibited A549 cell adhesion, migration and invasion in a concentration-dependent manner. Western blotting and gelatin zymography analysis revealed that PPSS inhibited the expression and secretion of MMP-2 and MMP-9 in A549 cells. Conclusions: PPSS has the potential to suppress the migration, adhesion and invasion of A549 cells. PPSS could be a potential candidate for interventions against lung cancer metastases.

육계로부터 분리한 병원성 세균에 대한 봉독의 항균효과 (Antibacterial effects of purified bee venom against some pathogenic bacteria isolated from dead chickens)

  • 한상미;김세건;홍인표;우순옥;장혜리;이경우
    • 한국동물위생학회지
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    • 제39권3호
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    • pp.159-166
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    • 2016
  • Clostridium perfringens, Salmonella thyphimurium and S. Montevideo isolated from the intestines of dead broiler chickens in Korea were tested for antibacterial effects to purifed bee venom. Purified bee venom from Apis mellifera L. has been used as natural antimicrobial compounds in pigs, cows, dairy cattle and chicken farms in Korea. To investigate antibacterial effect of purified bee venom was evaluated by agar well diffusion method, minimum inhibitory concentraion (MIC), minimum bactericidal concentration (MBC), and postantibiotic effect (PAE). Purified bee venom exhibited significant inhibition of bacterial growth of C. perfringens, S. thyphimurium and S. Montevideo with MIC value of 0.85, 0.68 and $0.69{\mu}g/mL$, respectively. The MBC value of purified bee venom against C. perfringens, S. thyphimurium and S. Montevideo were 3.33, 2.66 and $2.86{\mu}g/mL$. Furthermore, the results of PAE values against C. perfringens, S. thyphimurium and S. Montevideo showed the bacterial effect with 3.5, 4.0 and 3.5 hr. Stability of pufifed bee venom at acidity from pH 1 to pH 8 for 24 hr was the antibacterial activity for C. perfringens, S. thyphimurium and S. Montevideo and melittin contents. Also purified bee venom processed through the heating for 15 min, there was no signification loss of the antibacterial activity and melittin at below $100^{\circ}C$. These results obtained in this study suggest that purified bee venom might be utilized as a feed additive in poultry diets.

위경탕(葦莖湯).가미위경탕(加味葦莖湯)의 B16-Fo에 대(對)한 항종양(抗腫瘍) 효과(效果)와 조직(組織) 변화(變化) (Effects of Wekyungtang and Kami-Wekyungtang on Pulmonary Tumor Cells and the Changes of Tissues)

  • 김현수;김성훈
    • 대한한의학회지
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    • 제16권2호
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    • pp.365-385
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    • 1995
  • In order to prove the antitumor effect of Wekyungtang(WKT) that was originated in Bigeubchunkeumyobang(備急千金要方), Wekyungtang with Houttuyniae Herba(WKT-I) and Wekyungtang with Oldenlandiae diffusae Herba(WKT-II) experimentally, the studies were done, We evaluated the cytotoxic activity against B16- Fo as well as the synergistic effects with anticancer drugs such as cyclophophamide (CPM), cisplatin(CPT) and 5-fluorouracil (5-FU) in vitro and measured body weight, survival time, hematological changes, changes of tissues in G57BL/6 implanted with B16-Fo. The results were obtained as follows: 1. In vitro cytotoxic effect against B16-Fo was shown in all groups as compared with control group, but the concentrations showing inhibitory growth rate below 55% of control was recognized in all concentrations of Wekyungtang(WKT) against B16-Fo and also concentration of $10^4$g/ml above in all group with cyclophophamide (CPM), concentration of $10^3$g/ml in Wekyungtang(WKT-l) with cisplatin(CPT) in synergistic effect, 2. In vivo body and tumor weight were significantly suppressed in all groups as compared with control group 3. The number of platelet, WBC, RBC were significantly increased in all groups, platelet aggregation was significantly increased in WKT-I and WKT-II as compared with control group. 4. In changes of tissues heavy infiltration oh cancer was shown in portal vein, pulmonary tissue, vein, peribronchiole, aveoli, while WKT-I was effective in antihepatic metastasis and WKT-II in pulmonary matastasis. From above results it was concluded that wekyungtang(WKT), wekyungtang with Houttuyniae Herba(WKT-I) and wekyungtang with Oldenlandiae diffusae Herba(WKT -II) had antitumor effect, and also wekyungtang combined with Houttuyniae Herba or Oldenlandiae diffusae Herba were more effective than wekyungtang only and also cyclophophamide (CPM), cisplatin(CPT) showed the more synergistic effect which suggests the necessity of continuous study on the mechanism of antitumor action of Houttuyniae Herba or Oldenlandiae diffusae Herba.

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바나나 과실 함유탄닌이 소화효소 작용에 미치는 영향 (Effect of Condensed Tannins Prepared from Banana (Musa Sapientum L.) fruit on Digestive Enzyme In vitro)

  • 정정한;류충호;조영수
    • Applied Biological Chemistry
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    • 제39권6호
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    • pp.477-481
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    • 1996
  • 바나나 과실을 시중에서 구입하여 미숙과실과 황숙과실로 구별하고 이것들을 과육부분과 과피부분으로 나누어서 동결건조 및 열풍건조시켜 실험 시료로서 사용하였다. 탄닌 함량을 분석한 결과 황숙과실 보다도 미숙과실에서 높았으며, 과육보다는 과피에서 열풍건조 보다는 동결건조시킨 시료에서 높은 경향을 나타내었다. 탄닌의 분획은 Sephadex LH-20칼럼을 사용하여 분획하였다. 바나나 과실에 함유하고 있는 탄닌은 prodelphinidin, procyanidin을 구성 단위로 하는 proanthocyanidin류의 축합성 탄닌으로 이러한 탄닌은 소화효소인 trypsin(EC 3. 1. 1. 3), ${\alpha}-amylase$(EC 3. 4. 21. 4), lipase(EC 3. 2. 1. 1)에 대하여 in vitro에 있어서 저해작용을 가지고 있는 것이 확인되었으며 또한 탄닌은 중합도가 높을수록 저해율이 높다는 것이 확인되었다.

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