• Title/Summary/Keyword: Apoptosis induction

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Herbal medicine In-Jin-Ho-Tang as a potential anti-cancer drug by induction of apoptosis in human hepatoma HepG2 cells. (사람 간암 세포주인 HepG2에 대한 인진호탕(茵陳蒿湯)의 항암 효과)

  • Yun, Hyun-Joung;Kim, Byung-Wan;Lee, Chang-Hyun;Jung, Jae-Ha;Heo, Sook-Kyung;Park, Won-Hwan;Park, Sun-Dong
    • The Korea Journal of Herbology
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    • v.22 no.3
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    • pp.27-37
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    • 2007
  • Objectives: Hepatocellular carcinoma is the most common primary malignant tumor of the liver worldwide. In-Jin-Ho-Tang(IJHT) has been used as a traditional Chinese herbal medicine since ancient time. and today it is widely applied as a medication for jaundice which is associated with inflammation in liver. In this study, I investigated whether methanol extract of IJHT induced HepG2 cancer cell death. Methods: Cytotoxic activity of IJHT on HepG2 cells was using XTT assay. Apoptosis induction by Ros A in HCT116 cells was verified by the induction of cleavage of poly ADP-ribose polymerase (PARP). and activation of caspase-3, -8 and -9. The release of cytochrome c from mitochondria to cytosol. the level of Bcl-2 and Bax and the expression of p53 and p21 were examined by western blotting analysis. Furthermore, MAPKs activation was analyzed by western blotting analysis. Results: IJHT induced apoptosis in HepG2 cells. And treatment of IJHT resulted in the release of cytochrome c into cytosol, decreased anti-apoptotic Bcl-2, and increased pri-apoptotic Bax expression. IJHT markedly inactivated extracellular signal-regulated kinase (ERK1/2), and activated p38 mitogen-activated protein (MAP) kinase. Sodium orthovanadate (SOV), a phosphatase inhibitor, to reverse IJHT-induced ERK1/2 inactivation and SB203580, a specific p38 MAP Kinase inhibitor efficiently blocked apoptosis of HepG2. Thus, IJHT induces apoptosis in HepG2 cells via MAP kinase modulation. Conclusion: These results indicated that IJHT has some potential for use as an anti-cancer agent.

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Post-cancer Treatment with Condurango 30C Shows Amelioration of Benzo[a]pyrene-induced Lung Cancer in Rats Through the Molecular Pathway of Caspase-3-mediated Apoptosis Induction -Anti-lung cancer potential of Condurango 30C in rats-

  • Sikdar, Sourav;Mukherjee, Avinaba;Bishayee, Kausik;Paul, Avijit;Saha, Santu Kumar;Ghosh, Samrat;Khuda-Bukhsh, Anisur Rahman
    • Journal of Pharmacopuncture
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    • v.16 no.3
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    • pp.11-22
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    • 2013
  • Objectives: The present investigation aimed at examining if post-cancer treatment with a potentized homeopathic drug, Condurango 30C, which is generally used to treat oesophageal cancer, could also show an ameliorating effect through apoptosis induction on lung cancer induced by benzo[a]pyrene (BaP) in white rats (Rattus norvegicus). Methods: Lung cancer was induced after four months by chronic feeding of BaP to rats through gavage at a dose of 50 mg/kg body weight for one month. After four months, the lung-cancer-bearing rats were treated with Condurango 30C for the next one ($5^{th}$), two ($5^{th}-6^{th}$) and three ($5^{th}-7^{th}$) months, respectively, and were sacrificed at the corresponding time-points. The ameliorating effect, if any, after Condurango 30C treatment for the various periods was evaluated by using protocols such as histology, scanning electron microscopy (SEM), annexinV-FITC/PI assay, flow cytometry of the apoptosis marker, DNA fragmentation, reverse transcriptase-polymerase chain reaction (RT-PCR), immunohistochemistry, and western blot analyses of lung tissue samples. Results: Striking recovery of lung tissue to a near normal status was noticed after post-cancerous drug treatment, as evidenced by SEM and histology, especially after one and two months of drug treatment. Data from the annexinV-FITC/PI and DNA fragmentation assays revealed that Condurango 30C could induce apoptosis in cancer cells after post-cancer treatment. A critical analysis of signalling cascade, evidenced through a RT-PCR study, demonstrated up-regulation and down-regulation of different pro- and anti-apoptotic genes, respectively, related to a caspase-3-mediated apoptotic pathway, which was especially discernible after one-month and two-month drug treatments. Correspondingly, Western blot and immunohistochemistry studies confirmed the ameliorative potential of Condurango 30C by its ability to down-regulate the elevated epidermal growth factor receptor (EGFR) expression, a hallmark of lung cancer. Conclusion: The overall result validated a positive effect of Condurango 30C in ameliorating lung cancer through caspase-3-mediated apoptosis induction and EGFR down-regulation.

β-lapachone-Induced Apoptosis of Human Gastric Carcinoma AGS Cells Is Caspase-Dependent and Regulated by the PI3K/Akt Pathway

  • Yu, Hai Yang;Kim, Sung Ok;Jin, Cheng-Yun;Kim, Gi-Young;Kim, Wun-Jae;Yoo, Young Hyun;Choi, Yung Hyun
    • Biomolecules & Therapeutics
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    • v.22 no.3
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    • pp.184-192
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    • 2014
  • ${\beta}$-lapachone is a naturally occurring quinone that selectively induces apoptotic cell death in a variety of human cancer cells in vitro and in vivo; however, its mechanism of action needs to be further elaborated. In this study, we investigated the effects of ${\beta}$-lapachone on the induction of apoptosis in human gastric carcinoma AGS cells. ${\beta}$-lapachone significantly inhibited cellular proliferation, and some typical apoptotic characteristics such as chromatin condensation and an increase in the population of sub-G1 hypodiploid cells were observed in ${\beta}$-lapachone-treated AGS cells. Treatment with ${\beta}$-lapachone caused mitochondrial transmembrane potential dissipation, stimulated the mitochondria-mediated intrinsic apoptotic pathway, as indicated by caspase-9 activation, cytochrome c release, Bcl-2 downregulation and Bax upregulation, as well as death receptor-mediated extrinsic apoptotic pathway, as indicated by activation of caspase-8 and truncation of Bid. This process was accompanied by activation of caspase-3 and concomitant with cleavage of poly(ADP-ribose) polymerase. The general caspase inhibitor, z-VAD-fmk, significantly abolished ${\beta}$-lapachone-induced cell death and inhibited growth. Further analysis demonstrated that the induction of apoptosis by ${\beta}$-lapachone was accompanied by inactivation of the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. The PI3K inhibitor LY29004 significantly increased ${\beta}$-lapachone-induced apoptosis and growth inhibition. Taken together, these findings indicate that the apoptotic activity of ${\beta}$-lapachone is probably regulated by a caspase-dependent cascade through activation of both intrinsic and extrinsic signaling pathways, and that inhibition of the PI3K/Akt signaling may contribute to ${\beta}$-lapachone-mediated AGS cell growth inhibition and apoptosis induction.

Induction of Apoptosis and G2/M Cell Cycle Arrest by Cordycepin in Human Prostate Carcinoma LNCap Cells (Cordycepin에 의한 LNCap 인체 전립선 암세포의 apoptosis 및 G2/M arrest 유발)

  • Lee, Hye Hyeon;Hwang, Won Deok;Jeong, Jin-Woo;Park, Cheol;Han, Min Ho;Hong, Su Hyun;Jeong, Yong Kee;Choi, Yung Hyun
    • Journal of Life Science
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    • v.24 no.1
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    • pp.92-97
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    • 2014
  • Cordycepin, an active component originally isolated from the traditional medicine Cordyceps militaris, is a derivative of the nucleoside adenosine, which has been shown to possess a number of pharmacological properties, including antioxidant and anti-inflammatory activities, immunological stimulation, and antitumor effects. This study was conducted on cultured human prostate carcinoma LNCap cells to elucidate the possible mechanisms by which cordycepin exerts its anticancer activity, which, until now, has remained poorly understood. Cordycepin treatment of LNCap cells resulted in dose-dependent inhibition of cell growth and the induction of apoptotic cell death as detected by an MTT assay, cleavage of poly ADP-ribose polymerase, and annexin V-FITC staining. Flow cytometric analysis revealed that cordycepin resulted in G2/M arrest in cell cycle progression and downregulation of cyclin B1 and cyclin A expression in a concentration-dependent manner. Moreover, the incubation of cells with cordycepin caused a striking induction in the expression of the cyclin-dependent kinase (CDK) inhibitor p21Waf1/Cip1 without affecting the expression of the tumor suppressor p53. It also resulted in a significant increase in the binding of CDK2 and CDC2 to p21. These findings suggest that cordycepin-induced G2/M arrest and apoptosis in human prostate carcinoma cells is mediated through p53-independent upregulation of the CDK inhibitor p21.

Activation of apoptotic protein in U937 cells by a component of turmeric oil

  • Lee, Yong-Kyu
    • BMB Reports
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    • v.42 no.2
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    • pp.96-100
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    • 2009
  • Aromatic (ar)-turmerone from turmeric oil displays anti-tumorigenesis activity that includes inhibited cell proliferation. This study investigated ar-turmerone-mediated apoptotic protein activation in human lymphoma U937 cells. Ar-turmerone treatment inhibited U937 cell viability in a concentration-dependent fashion, with inhibition exceeding 84%. Moreover, the treatment produced nucleosomal DNA fragmentation and the percentage of sub-diploid cells increased in a concentration-dependent manner; both are hallmarks of apoptosis. The apoptotic effect of ar-turmerone was associated with the induction of Bax and p53 proteins, rather than Bcl-2 and p21. Activation of mitochondrial cytochrome c and caspase-3 demonstrated that the activation of caspases accompanied the apoptotic effect of ar-turmerone, which mediated cell death. These results suggest that the apoptotic effect of ar-turmerone on U937 cells may involve caspase-3 activation through the induction of Bax and p53, rather than Bcl-2 and p21.

Induction of G1 arrest and apoptosis mediated by a novel nucleoside analog, LJ-331 in human leukemia HL-60 cells

  • Lee, Eun-Jin;Shin, Dea-Hong;Jeong, Lak-Shin;Lee, Sang-Kook
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 2003.11a
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    • pp.86-86
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    • 2003
  • In a continuous effort to develop novel anticancer agents we newly synthesized and evaluated the antitumor activity of nucleoside analogues. One analogue, 4 - [2-Chlor-6- (3-iodo- benzy lamino) -purin -9-yl]- 2,3-dihydroxy-cyclopentanecarbo xylic acid methylamide (LJ-331), has been shown to exert a potent inhibition of human cancer cell growth in vitro including human lung (A549), stomach (SNU-638) and leukemia (HL-60) cancer cells. Following mechanism of action study revealed that LJ - 331induces cell cycle arrest at the G1 phase in HL-60 cells and evokes apoptotic phenomena such as an increase in DNA ladder intensity and chromatin condensation by a dose- and time-dependent manner. LJ-331 also activated the caspase-3 activity in HL-60. This result suggests that the growth inhibition of human cancer cells by LJ-331 might be related to the cell cycle arrest and induction of apoptosis.

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Induction of apoptosis by dihydro-N-caffeoyltyramine on human leukemia cells

  • Choi, Chul-Yung;Kim, Ji-Young;Lee, Kyung-Jin;Oh, Duk-Hee;Han, Song-Hee;Woo, Eun-Rhan;Jeong, Hye-Gwang
    • Proceedings of the PSK Conference
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    • 2003.10b
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    • pp.120.3-121
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    • 2003
  • Lycii Radicis Cortex, the root bark of Lycium chinense Miller (Solanaceae) is used in oriental medicine as a tonic and is reported to exhibit hypotensive, hypoglycemic, and antipyretic activity. Recently, we have isolated dihydro-N-caffeoyltyramine, a phenolic amide, from the Lycii Radicis Cortex. Treatment with dihydro-N-caffeoyltyramine significantly inhibited the proliferation of human leukemia cell lines HL-60 in a dose-dependent manner. We found also that the growth inhibition of HL-60 by dihydro-N-caffeoyltyramine is associated with induction of apoptosis of cells. (omitted)

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PD98059 Induces the Apoptosis of Human Cervical Cancer Cells by Regulating the Expression of Bcl2 and ERK2

  • Yang, Eun-Ju;Chang, Jeong-Hyun
    • Biomedical Science Letters
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    • v.17 no.4
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    • pp.291-295
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    • 2011
  • PD98059 is the specific inhibitor of extracellular signaling-regulated kinase (ERK) kinase (MEK). ERK is involved in a mitogen-activated protein kinase (MAPK) cascade controlling cell growth and differentiation. Although the inhibition of ERK is known to induce cell death in various cell lines, this effect is still controversial and the role of PD98059 on the death of HeLa $S_3$ cells, a subclone of the cervical cancer cell line, is not well understood. The apoptosis of HeLa $S_3$ cells increased after the treatment of 50 ${\mu}M$ PD98059. The induction of apoptosis by PD98059 was occurred in a time- and a dose-dependent manners. The expression of Bcl-2 was reduced in accordance with decrease of ERK2 expression. Taken together, these results indicate that PD98059 has a cytotoxicity in HeLa $S_3$ cells and it may be used as a potential target for the treatment of cervical cancer.

Flavonoid Fraction Purified from Rhus verniciflua Stokes Actively Inhibits Cell Growth Via Induction of Apoptosis in Mouse Tumorigenic Hepatocytes

  • Lee, Jeong-Chae
    • Natural Product Sciences
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    • v.10 no.2
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    • pp.74-79
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    • 2004
  • Dietary flavonoids are currently receiving considerable attention in developing novel cancer-preventive approaches because of their potential capacities to actively induce apoptosis of cancer cells. In our previous report, a flavonoid fraction, which consisted mainly of protocatechuic acid, fustin, fisetin, sulfuretin, and butein and named RCMF (RVS chloroform-methanol fraction), was prepared from a crude acetone extract of Rhus verniciflua Stokes (RVS) that is traditionally used as food additive and herbal medicine. In this study, we evaluated the effects of the RCMF on cell proliferation and apoptosis using SV40-transformed tumorigenic hepatocytes, BNL SV A.8. Tritium uptake assay showing the proliferative capacity of the cells was strongly suppressed in the presence of RCMF. This anti-proliferative effect was further confirmed through trypan blue exclusion. RCMF-mediated suppression of cell growth was verified to be apoptotic, based on the increase in DNA fragmentation, low fluorescence intensity in nuclei after propidium iodide staining, and the appearance of DNA laddering. Collectively, this study demonstrated that RCMF can be approached as a potential agent that is capable of significantly inhibiting cell growth of hepatic cancer cells.