• The Journal of Internal Korean Medicine
• /
• v.29 no.1
• /
• pp.42-66
• /
• 2008

Aconiti Tuber is a traditional medicinal plant generally used in Oriental medicine therapy. In this study, we investigated the biochemical mechanisms of anti-proliferative effects by the methanol extract of Aconiti tuber (MEBJ) in Caki-1 human renal cell carcinoma cells. It was found that MEBJ could inhibit, in a dose-dependent manner, cell growth which was associated with apoptotic cell death such as formation of apoptotic bodies, DNA fragmentation and increased populations of apoptotic-sub G1 phase. Apoptosis of Caki-1 cells by MEBJ was associated with an up-regulation of pro-apoptotic Bax expression, and a down-regulation of anti-apoptotic Bcl-2 in a dose-dependent manner; however, the levels of IAP family were not affected. MEBJ treatment also induced the proteolytic activation of caspase-3 and -8, and a inhibition of poly(ADP-ribose) polymerase (PARP) and $PLC{\gamma}1$ protein. Furthermore, MEBJ treatment caused a dose-dependent inhibition of iNOS and cyclooxygenase-2 (Cox-2). Though further studies will be needed to identify the active compounds that confer the anti-cancer activity of MEBJ, the present findings provide important new insights into the possible molecular mechanisms of the apoptotic activity of MEBJ in cancer cells.

• Proceedings of the PSK Conference
• /
• 2002.10a
• /
• pp.319.1-319.1
• /
• 2002

Yomogin. an eudesmane sesquiterpene isolated from Artemisia princeps, was found to induce apoptosis in human promyelocytic leukaemia, HL -60 cell with characteristic apoptotic features like nuclear condensation, apoptotic body formation, flipping of membrane phosphatidylserine, release of mitochondrial cytochrome c and caspase-8. -9. and -3 activation. Furthermore. early yomogin-induced cytochrome c release was not affected by the caspase inhibitor Z-VAd fmk and preceded loss of mitochondrial membrane potential. The results suggest that induction of apoptosis by yomogin may provide a pivotal mechanism for their cancer chemopreventive function.

• Proceedings of the PSK Conference
• /
• 2003.10b
• /
• pp.134.2-135
• /
• 2003

We examined the minimal amino acid sequence of bovine lactoferricin (Lfcin-B), a cationic peptide corresponding to residues 17-41 near the N-terminus of bovine lactoferrin, to induce apoptosis in THP-l human monocytic leukemic cells using synthetic peptides. A synthetic peptide (Lfc-17/29, amino acid sequence; FKCRRWQWRMKKL) which is consist of 13 amino acids near the N-terminus of Lfcin-B induced cell death in THP-1 cells in a dose-dependent manner, showing apparent apoptotic changes such as hypodiploid forms of genomic DNA and apoptotic DNA fragmentation. (omitted)

• Korean Journal of Microbiology
• /
• v.38 no.3
• /
• pp.213-220
• /
• 2002

Inducible expression system for the three structural proteins, capsid (C), precursor membrane (prM/M), and envelop (E) of Japanese encephalitis virus (JEV) was established in BHK-21 cells. Doxycycline, a tetracycline analog, was utilized as an inducer. Transfectants BHK-21/IV (vector only), BHK-21/IC (for C), BHK-21/IP3 (for prM), and BHK-21/IE1 (for E) were selected and cloned in the presence of G4l8 or hygromycin. Transcribed mRNAs for the corresponding genes were observed after doxycycline induction. Effects by the JEV structural gene expression on the transfectants were monitored via cell growth, chromatin condensation, internucleosomal DNA fragmentation, and DNA contents analyses. Clear cell growth retardation and chromatin condensation were observed in all three transfectants while only BHK-2/IC corresponded to the induction status in the DNA fragmentation and DNA content analyses. Combined results, therefore, suggested that JEV capsid protein should be one of the direct and independent factors in apoptotic cell death induced by IEV infection.

• Biomolecules & Therapeutics
• /
• v.16 no.2
• /
• pp.95-99
• /
• 2008

Apoptosis is essential for a variety of pathophysiological progress. Apoptosis induction by various agents changes cellular morphology, DNA content and lipid membrane composition. Recently, sphingosine 1-phosphate (S1P) is avidly released from not only platelets and erythrocytes but vascular endothelium. Here we established S1P releasing cells by deleting S1P lyase (F9-12 cells). We observed apoptosis induction by the treatment of fumonisin B1 (FB1) in F9-12 cells but not in F9 wild-type cells. We measured high amounts of accumulated S1P and dihydroS1P (DHS1P) in FB1-induced apoptotic F9-12 cells. We also showed DHS1P release in an early stage of the apoptosis induction by FB1 but not by phorbol 12-myristate 13-acetate (PMA)-induced apoptosis, suggesting differential apoptotic processes.

• The Journal of Korean Obstetrics and Gynecology
• /
• v.18 no.3
• /
• pp.77-91
• /
• 2005

Purpose : Trichosanthis Radix is traditional medical herb which has been shown to inhibit tumor cell proliferation. In this study, the effects of Trichosanthis Radix extract were investigated on inducing growth inhibition and apoptosis of human uterine cervical carcinoma cells. Methods : Human uterine cervical carcinoma cells line, ME-180, was used for the study. The cells were treated with varying concentrations of Trichosanthis Radix extract. Cell growth and inhibitory rate were measured by MTT assay. Apoptosis induction was detected by fluorescence microscopy, DNA ladder formation and flow cytometry. Results : Trichosanthis Radix extract inhibited the growth of human uterine cervical carcinoma cells in a dose-dependent manner. It induced ME-180 cells to undergo apoptosis including fragmented nuclei and nucleosome-sized DNA fragmentation. Flow cytometric analysis showed the increasing rate of apoptotic cells by Trichosanthis Radix extract. Reduction of mitochondrial membrane potential and increase in caspase-3 activity and were found in ME-180 cells treated with Trichosanthis Radix extract. Conclusion : Our data suggest that Trichosanthis Radix extract inhibit the growth and proliferation of ME-180 cells by apoptotic induction and facilitates its activity via caspase-3 activation initiated by depolarization of mitochondria.

• Journal of Life Science
• /
• v.22 no.6
• /
• pp.815-822
• /
• 2012

Piceatannol (trans-3,4,3',5'-tetrahydroxystilbene), a natural stilbene, is an analogue of resveratrol. Although recent experimental data have revealed the health benefit potency of piceatannol, the molecular mechanisms underlying the anti-cancer activity have not yet been studied in detail. In the present study, the further possible mechanisms by which piceatannol exerts its pro-apoptotic action in cultured human lung cancer A549 cells were investigated. Exposure of A549 cells to piceatannol resulted in growth inhibition and induction of apoptosis. Apoptosis induction of A549 cells by piceatannol showed correlation with proteolytic activation of caspase-3, -8, and -9, and concomitant degradation of activated caspase-3 target proteins such as poly (ADP-ribose) polymerase, phospholipase C-${\gamma}1$, ${\beta}$-catenin, and Inhibitor caspase-activated DNase. The increase in apoptosis by piceatannol treatment was also associated with an increase of pro-apoptotic Bax expression and decrease of anti-apoptotic Bcl-2 and Bcl-xL expression, and caused down-regulation of the inhibitor of apoptosis protein family members and up-regulation of Fas and Fas legend. In addition, piceatannol treatment markedly inhibited the expression of mRNA and proteins of inducible nitric oxide (NO) synthase, and the levels of NO production were progressively down-regulated by piceatannol treatment in a dose-dependent fashion. The results indicate that piceatannol may have therapeutic potential against human gastric cancer cells.

• Asian Pacific Journal of Cancer Prevention
• /
• v.13 no.12
• /
• pp.6369-6374
• /
• 2012

Vitexicarpin (3', 5-dihydroxy-3, 4', 6, 7-tetramethoxyflavone), a polymethoxyflavone isolated from Viticis Fructus (Vitex rotundifolia Linne fil.), has long been used as an anti-inflammatory herb in traditional Chinese medicine. It has also been reported that vitexicarpin can inhibit the growth of various cancer cells. However, there is no report elucidating its effect on human prostate carcinoma cells. The aim of the present study was to examine the apoptotic induction activity of vitexicarpin on PC-3 cells and molecular mechanisms involved. MTT studies showed that vitexicarpin dose-dependently inhibited growth of PC-3 cells with an $IC_{50}{\sim}28.8{\mu}M$. Hoechst 33258 staining further revealed that vitexicarpin induced apoptotic cell death. The effect of vitexicarpin on PC-3 cells apoptosis was tested using prodium iodide (PI)/Annexin V-FITC double staining and flow cytometry. The results indicated that vitexicarpin induction of apoptotic cell death in PC-3 cells was accompanied by cell cycle arrest in the G2/M phase. Furthermore, our study demonstrated that vitexicarpin induction of PC-3 cell apoptosis was associated with upregulation of the proapoptotic protein Bax, and downregulation of antiapoptotic protein Bcl-2, release of Cytochrome c from mitochondria and decrease in mitochondrial membrane potential. Our findings suggested that vitexicarpin may become a potential leading drug in the therapy of prostate carcinoma.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.23 no.6
• /
• pp.1314-1319
• /
• 2009

In previous study, we have shown that continentalic acid (CA) isolated from Aralia continentalis induced the growth inhibition and apoptosis in HepG2 cells. In this study, we examine the effects of CA from A. continentalis on growth inhibition and apoptosis induction in human leukemia HL-60 and mouse fibroblast NIH 3T3 cell lines. The results demonstrated that CA decreased cell growth of leukemia HL-60 cells but not human HaCaT keratinocytes, assessed with the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] and LDH (lactate dehydrogenase) assay. Flow cytometric analysis of mouse fibroblast cell lines exposed to CA showed that apoptotic cells increased in a time- and dose-dependent manner. Treatment with CA decreased the number of normal cells and increased the number of early apoptotic and late apoptotic cells in a dose-dependent manner. The induction of apoptosis in mouse cell lines by CA was mediated through the activation of caspase-3, Bak, and Bax and the down-regulation of Bcl-2. Our results suggest that CA efficiently induces apoptosis in human leukemia cells.

• Archives of Pharmacal Research
• /
• v.27 no.1
• /
• pp.68-76
• /
• 2004

Mistletoe lectin has been reported to induce apoptosis in different cancer cell lines in vitro and to show antitumor activity against a variety of tumors in animal models. We previously demonstrated the Korean mistletoe lectin (Viscum album var. coloratum, VCA)-induced apoptosis by down-regulation of Bcl-2 and telomerase activity and by up-regulation of Bax through p53- and p21-independent pathway in hepatoma cells. In the present study, we observed the induction of apoptotic cell death through activation of caspase-3 and the inhibition of telomerase activity through transcriptional down-regulation of hTERT in the VCA-treated A253 cells. We also observed the inhibition of telomerase activity and induction of apoptosis resulted from dephosphorylation of Akt in the survival signaling pathways. In addition, combining VCA with the inhibitors of phosphatidylinositol 3-kinase (PI3-kinase) upstream of Akt, wortmannin and LY294002 showed an additive inhibitory effect of telomerase activity. In contrast, the inhibitor of protein phosphatase 2A (PP2A), okadaic acid inhibited VCA-induced dephosphorylation of Akt and inhibition of telomerase activity. Taken together, VCA induces apoptotic cell death through Akt signaling pathway in correlated with the inhibition of telomerase activity and the activation of caspase-3. From these results, together with our previous studies, we suggest that VCA triggers molecular changes that resulting in the inhibition of cell growth and the induction of apoptotic cell death of cancer cells, which suggest that VCA may be useful as chemotherapeutic agent for cancer cells.