• Journal of the Society of Cosmetic Scientists of Korea
• /
• v.42 no.2
• /
• pp.153-162
• /
• 2016

In this study, we investigated the moisturizing effects of collagen extract from jellyfish. The mositurizing effects were measured by the caspase 14 expression, filaggrin, hyaluronan synthase-3 (HAS-3), aquaporin-3 (AQP-3) and desmocollin (DSC). As a results, effect of caspase 14 mRNA expression of collagen extract are similar to that of retinoic acid (RA) which is a reference control. And the collagen extract showed inhibitory of filaggrin, HAS-3, AQP-3 and DSC mRNA expression of 211.7%, 139.9%, 212.5% and 116.8% respectively, at the concentration of 2%. Therefore, our study suggested that jellyfish collagen extract has considerable potential as a cosmetics ingredient with moisturizing effect.

• Journal of Life Science
• /
• v.28 no.7
• /
• pp.778-785
• /
• 2018

Autophagy is a complex signaling process and has been implicated in tumor suppression and anticancer therapy resistance. Autophagy can produce tumor-suppressive effect by inducing autophagic cell death, either in collaboration with apoptosis. In this current study, we found that celecoxib (CCB), a nonsteroidal anti-inflammatory drug (NSAID) with multifaceted effects, induced autophagy including enhanced LC3 conversion (LC3-I to LC3-II) and reduced autophagy substrate protein p62 level in multidrug-resistant (MDR) cancer cells. CCB sensitized human multidrug resistant (MDR) cancer cells to the ansamycin-based HSP90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG), a benzoquinoid ansamycin, which causes the degradation of several oncogenic and signaling proteins, by inducing autophagic cell death and apoptosis. CCB significantly augmented 17-AAG-mediated level of LC3-II/LC-I, indicating the combined effect of 17-AAG and CCB on the induction of autophagy. Autophagic degradation of mutant p53 (mutp53) and activation of caspase-3 in 17-AAG-treated MDR cells were accelerated by CCB. Inhibition of caspase-3-mediated apoptotic pathway by Z-DEVD-FMK, a caspase-3 inhibitor, did not completely block CCB-induced cell death in MCF7-MDR cells. In addition, treatment of MDR cells with Z-DEVD-FMK failed to prevent activation of autophagy by combined treatment with 17-AAG and CCB. Based on our findings, the ability of clinically used drug CCB to induce autophagy has important implications for its development as a sensitizing agent in combination with Hsp90 inhibitor of MDR cancer.

• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.5
• /
• pp.1833-1837
• /
• 2015

An aristolactam-type alkaloid, isolated from Orophea enterocarpa, is enterocarpam-III (10-amino-2,3,4,6-tetramethoxyphenanthrene-1-carboxylic acid lactam). It is cytotoxic to various human and murine cancer cell lines; however, the molecular mechanisms remain unclear. The aims of this study were to investigate cytotoxic effects on and mechanism (s) of human cancer cell death in human hepatocellular carcinoma HepG2 and human invasive breast cancer MDA-MB-231 cells compared to normal murine fibroblast NIH3T3 cells. Cell viability was determined by MTT assay to determine $IC_{10}$, $IC_{20}$ and $IC_{50}$ levels, reactive oxygen species (ROS) production with 2',7'-dichlorohydrofluorescein diacetate and the caspase-3, -8 and -9 activities using specific chromogenic (p-nitroaniline) tetrapeptide substrates, viz., DEVD-NA, IETD-NA and LEHD-NA and employing a microplate reader. Mitochondrial transmembrane potential (MTP) was measured by staining with 3, 3'-dihexyloxacarbocyanine iodide ($DiOC_6$) and using flow cytometry. The compound was cytotoxic to HepG2 and MDA-MB-231 cells with the $IC_{50}$ levels of $26.0{\pm}4.45$ and $51.3{\pm}2.05{\mu}M$, respectively. For murine normal fibroblast NIH3T3 cells, the $IC_{50}$ concentration was $81.3{\pm}10.1{\mu}M$. ROS production was reduced in a dose-response manner in HepG2 cells. The caspase-9 and -3 activities increased in a concentration-dependent manner, whereas caspase-8 activity did not alter, indicating the intrinsic pathway activation. Enterocarpam-III decreased the mitochondrial transmembrane potential (MTP) dose-dependently in HepG2 cells, suggesting that the compound induced HepG2 cell apoptosis via the mitochondrial pathway. In conclusion, enterocarpam-III inhibited HepG2 and MDA-MB-231 cell proliferation and induced human HepG2 cells to undergo apoptosis via the intrinsic (mitochondrial) pathway and induction of caspase-9 activity.

• The Korean Journal of Physiology and Pharmacology
• /
• v.26 no.6
• /
• pp.447-456
• /
• 2022

The present study was carried out to investigate the effect of Arctigenin on cell growth and the mechanism of cell death elicited by Arctigenin were examined in FaDu human pharyngeal carcinoma cells. To determine the apoptotic activity of Arctigenin in FaDu human pharyngeal carcinoma cells, cell viability assay, DAPI staining, caspase activation analysis, and immunoblotting were performed. Arctigenin inhibited the growth of cells in a dose-dependent manner and induced nuclear condensation and fragmentation. Arctigenin-treated cells showed caspase-3/7 activation and increased apoptosis versus control cells. FasL, a death ligand associated with extrinsic apoptotic signaling pathways, was up-regulated by Arctigenin treatment. Moreover, caspase-8, a part of the extrinsic apoptotic pathway, was activated by Arctigenin treatments. Expressions of anti-apoptotic factors such as Bcl-2 and Bcl-xL, components of the mitochondria-dependent intrinsic apoptosis pathway, significantly decreased following Arctigenin treatment. The expressions of pro-apoptotic factors such as BAX, BAD and caspase-9, and tumor suppressor -53 increased by Arctigenin treatments. In addition, Arctigenin activated caspase-3 and poly (ADP-ribose) polymerase (PARP) induced cell death. Arctigenin also inhibited the proliferation of FaDu cells by the suppression of p38, NF-κB, and Akt signaling pathways. These results suggest that Arctigenin may inhibit cell proliferation and induce apoptotic cell death in FaDu human pharyngeal carcinoma cells through both the mitochondria-mediated intrinsic pathway and the death receptor-mediated extrinsic pathway.

• The korean journal of orthodontics
• /
• v.48 no.4
• /
• pp.253-261
• /
• 2018

Objective: Orthodontic root resorption (ORR) due to orthodontic tooth movement is a difficult treatment-related adverse event. Caspases are important effector molecules for apoptosis. At present, little is known about the mechanisms underlying ORR and apoptosis in the cementum. The aim of the present in vivo study was to investigate the expression of tartrate-resistant acid phosphatase (TRAP), caspase 3, caspase 8, and receptor activator of nuclear factor kappa-B ligand (RANKL) in the cementum in response to a heavy or an optimum orthodontic force. Methods: The maxillary molars of male Wistar rats were subjected to an orthodontic force of 10 g or 50 g using a closed coil spring. The rats were sacrificed each experimental period on days 1, 3, 5, and 7 after orthodontic force application. And the rats were subjected to histopathological and immunohistochemical analyses. Results: On day 7 for the 50-g group, hematoxylin and eosin staining revealed numerous root resorption lacunae with odontoclasts on the root, while immunohistochemistry showed increased TRAP- and RANKL-positive cells. Caspase 3- and caspase 8-positive cells were increased on the cementum surfaces in the 50-g group on days 3 and 5. Moreover, the number of caspase 3- and caspase 8-positive cells and RANKL-positive cells was significantly higher in the 50-g group than in the 10-g group. Conclusions: In our rat model, ORR occurred after apoptosis was induced in the cementum by a heavy orthodontic force. These findings suggest that apoptosis of cementoblasts is involved in ORR.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.7
• /
• pp.2993-2999
• /
• 2014

Saccharina japonica is a family member of Phaeophyceae (brown macro-alga) and extensively cultivated in China, Japan and Korea. Here, the potential anti-cancer effect of n-hexane fraction of S. japonica was evaluated in SK-Hep1 human hepatocellular carcinoma cells. The N-hexane fraction reduced cell viability and increased the numbers of apoptotic cells in a both dose- and time-dependent manner. Apoptosis was activated by both caspase-dependent and independent pathways. The caspase-dependent cell death pathway is mediated by cell surface death receptors and activated caspase-8 amplified the apoptotic signal either through direct activation of downstream caspase-3 or pro-apoptotic proteins (Bad, Bax and Bak) subsequently leading to the release of cytochrome c. On the other hand, caspase-independent apoptosis appeared mediated by disruption of mitochondrial membrane potential and translocation of AIF to the nucleus where they induced chromatin condensation and/or large-scale DNA fragmentation. In addition, the n-hexane fraction induced endoplasmic reticulum (ER)-stress and cell cycle arrest. The results suggested that potential anti-cancer effects of n-hexane extract from S. japonica on SK-Hep1 cells.

• Fisheries and Aquatic Sciences
• /
• v.21 no.8
• /
• pp.22.1-22.7
• /
• 2018

Background: Apoptosis is a process of programmed cell death, and apoptosis defect results in serious diseases such as cancer. Apoptosis induction is one of the key mechanisms of anti-cancer agents. This study was aimed to find anti-prostate cancer compounds from marine-derived fungus Microsporum sp. Results: We found that physcion isolated from the fermentation broth extract of the marine fungus Microsporum sp. strain MFS-YL decreases the cell proliferation of PC3 human prostate cancer cells. Physcion induced cell apoptosis as determined by Annexin V/propidium iodide double staining. Physcion downregulated the anti-apopotoic proteins such as Ras, Bcl-xL, and Bcl-2, whereas upregulated the pro-apoptotic Bax. Physcion also activated caspase-3, caspase-8, and caspase-9. Conclusion: These results suggest that physcion from Microsporum sp. inhibits the proliferation of PC3 human prostate cancer cells via the pathway leading to apoptotic cell death. Physcion may be a potential candidate in the field of anticancer drug discovery against human prostate cancer.

• The Korean Journal of Physiology and Pharmacology
• /
• v.7 no.4
• /
• pp.199-205
• /
• 2003

Osteoblasts are affected by TNF-${\alpha}$ overproduction by immune cells during inflammation. It has been suggested that functional $NF-{\kappa}B$ sites are involved in TNF-${\alpha}$-induced bone resorption. Thus, we explored the effect of pyrrolidine dithiocarbamate (PDTC), which potently blocks the activation of nuclear factor $(NF-{\kappa}B)$, on the induction of TNF-${\alpha}$-induced activation of JNK/SAPK, AP-1, cytochrome c, caspase and apoptosis in MC3T3E1 osteoblasts. Pretreatment of the cells with PDTC blocked TNF-${\alpha}$-induced $NF-{\kappa}B$ activation. TNF-${\alpha}$-induced activation of AP-1, another nuclear transcription factor, was suppressed by PDTC. The activation of c-Jun N-terminal kinase, implicated in the regulation of AP-1, was also down regulated by PDTC. TNF-${\alpha}$-induced apoptosis, release of cytochrome c and subsequent activation of caspase-3 were abolished by PDTC. TNF-${\alpha}$-induced apoptosis was partially blocked by Ac-DEVD-CHO, a caspase-3 inhibitor, suggesting that caspase-3 is involved in TNF-${\alpha}$-mediated signaling through $NF-{\kappa}B$ in MC3T3E1 osteoblasts. Thus, these results demonstrate that PDTC, has an inhibitory effect on TNF-${\alpha}$-mediated activation of JNK/SAPK, AP-1, cytochrome c release and subsequent caspase-3, leading to the inhibition of apoptosis. Our study may contribute to the treatment of TNF-${\alpha}$-associated immune and inflammatory diseases such as rheumatoid arthritis and periodontal diseases.

• Asian Pacific Journal of Cancer Prevention
• /
• v.14 no.4
• /
• pp.2637-2641
• /
• 2013

6,8-Dihydroxy-7-methoxy-1-methyl-azafluorenone (DMMA), a purified compound from Polyalthia cerasoides roots, is cytotoxic to various cancer cell lines. The aims of this study were to demonstrate the type of cancer cell death and the mechanism(s) involved. DMMA inhibited cell growth and induced apoptotic death in human leukemic cells (HL-60, U937, MOLT-4), human breast cancer MDA-MB231 cells and human hepatocellular carcinoma HepG2 cells in a dose dependent manner, with $IC_{50}$ values ranging between 20-55 ${\mu}M$. DMMA also decreased cell viability of human peripheral blood mononuclear cells. The morphology of cancer cells induced by the compound after staining with propidium iodide and examined under a fluorescence microscope was condensed nuclei and apoptotic bodies. Mitochondrial transmembrane potential (MTP) was decreased after 24h exposure in all five types of cancer cells. DMMA-induced caspase-3, -8, and -9 activity was strongly induced in human leukemic HL-60 and MOLT-4 cells, while in U937-, MDA-MB231- and HepG2-treated cells there was partial induction of caspase. In conclusion, DMMA-induced activation of caspase-8 and -9 resulted in execution of apoptotic cell death in human leukemic HL-60 and MOLT-4 cell lines via extrinsic and intrinsic pathways.

• BMB Reports
• /
• v.47 no.7
• /
• pp.405-410
• /
• 2014

ZBTB3 belongs to the Zinc finger and BTB/POZ domain containing transcription factor family; however, its biological role has rarely been studied. We demonstrate for the first time, to our knowledge, that ZBTB3 is an essential factor for cancer cell growth via the regulation of the ROS detoxification pathway. Suppression of ZBTB3 using two different short hairpin RNAs in human melanoma, lung carcinoma, and breast carcinoma results in diminished cell growth. In addition, we found that suppression of ZBTB3 activates a caspase cascade, including caspase-9, -3, and PARP leading to cellular apoptosis, resulting from failed ROS detoxification. We identified that ZBTB3 plays an important role in the gene expression of ROS detoxification enzymes. Our results reveal that ZBTB3 may play a critical role in cancer cell growth via the ROS detoxification system. Therefore, therapeutic strategies that target ZBTB3 could be used in selective cancer treatments.