• YAKHAK HOEJI
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• v.45 no.2
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• pp.161-168
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• 2001

The possible mechanism of the antiproliferative and apoptotic effects of Boswellia carterri water extract were studied in HL-60 human leukemia cells. The cytotoxicity of HL-60 cells after the treatment of Boswellia carterii water extract showed dose- and time-dependent manner. The apoptotic effect of 300 $\mu$g/ml Boswellia carterii water extract was demonstrated by DNA laddering. The activity of caspase 3-1ike protease was markedly increased in HL-60 cells treated with Boswellia carterii water extract. Furthermore, the level of Bcl-2 was time-dependently reduced, whereas Bax protein level was enhanced by Boswellia carterii water extract treatment. In conclusion, our results suggest that apoptotic effect of Boswellia carterii water extract may partly mediated through activations of caspase-3 activity and Bax expression, and inhibition of Bcl-2 expression.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.338.2-338.2
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• 2002

Ceramide is a lipid second messenger that is involved in apoptotic cell death. In this study, we show that p38 MAPK plays an important role in the regulation of ceramide-induced apoptosis. We found that SB203580, a p38 kinase inhibitor, blocked the effects of ceramide to induce Bax translocation to mitochondria, activation of caspase-3, and DNA fragmentation. Furthermore. expression of a dominant negative form of p38 MAPK suppressed ceramide-induced Bax translocation, suggesting that p38 kinase activity is essential for Bax translocation. (omitted)

• Journal of Life Science
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• v.12 no.4
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• pp.469-476
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• 2002

The DNA topoismerase I inhibitor $\beta$-lapachone, the product of a tree from South America, is known to exhibit various biological properties, however the mechanisms of which are poorly understood. In the present report, we investigated the effects of $\beta$-lapachone on the growth of human prostate carcinoma DU-145 cells. Upon treatment with $\beta$-lapachone, a concentration-dependent inhibition of cell viability was observed and cells developed many of the hallmark features of apoptosis, including condensation of chromatin and DNA fragmentation. Flow cytometry analysis confirmed that $\beta$-lapachone increased populations of apoptotic-sub Gl phase. In addition, proteolytic cleavages of poly (ADP-ribose) polymerase (PARP) and $\beta$-catenin protein were observed after treatment of $\beta$-lapachone. These apoptotic effects of $\beta$-lapachone in DU-145 cells were associated with marked induction of Bax protein, however the levels of Bcl-2 expression were decreased in a dose-dependent manner.

• Proceedings of the PSK Conference
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• 2000.10a
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• pp.86-87
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• 2000

• Animal Bioscience
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• v.35 no.5
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• pp.763-777
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• 2022

Objective: Excessive lipid accumulation in adipocytes results in prevalence of obesity and metabolic syndrome. Curcumin (CUR), a naturally phenolic active ingredient, has been shown to have lipid-lowering effects. However, its underlying mechanisms have remained largely unknown. Therefore, the study aims to determine the effect of CUR on cellular lipid accumulation in porcine subcutaneous preadipocytes (PSPA) and to clarify novel mechanisms. Methods: The PSPA were cultured and treated with or without CUR. Both cell counting Kit-8 and lactate dehydrogenase release assays were used to examine cytotoxicity. Intracellular lipid contents were measured by oil-red-o staining extraction and triglyceride quantification. Apoptosis was determined by flow cytometry and the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-nick end labelling assay. Adipogenic and apoptosis genes were analyzed by quantitative polymerase chain reaction and Western blot. Results: The CUR dose-dependently reduced the proliferation and lipid accumulation of PSPA. Noncytotoxic doses of CUR (10 to 20 μM) significantly inhibited extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation and expression of adipogenic genes peroxisome proliferation-activity receptor-γ (PPAR-γ), CCAAT/enhancer binding protein-α, sterol regulatory element-binding protein-1c, adipocyte protein-2, glucose transporter-4 as well as key lipogenic enzymes fatty acid synthase and acetyl-CoA carboxylase, while ERK1/2 activation significantly reversed CUR-reduced lipid accumulation by increasing PPAR-γ. Furthermore, compared with differentiation induced media treated cells, higher dose of CUR (30 μM) significantly decreased the expression of AKT and B-cell lymphoma-2 (BCL-2), while increased the expression of BCL-2-associated X (BAX) and the BAX/BCL-2 expression ratio, suggesting triggered apoptosis by inactivating AKT and increasing BAX/BCL-2 ratio and Caspase-3 expression. Moreover, AKT activation significantly rescued CUR inhibiting lipid accumulation via repressing apoptosis. Conclusion: These results demonstrate that CUR is capable of suppressing differentiation by inhibiting ERK1/2-PPAR-γ signaling pathway and triggering apoptosis via decreasing AKT and subsequently increasing BAX/BCL-2 ratio and Caspase-3, suggesting that CUR provides an important method for the reduction of porcine body fat, as well as the prevention and treatment of human obesity.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.1
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• pp.167-173
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• 2005

To investigate the possible molecular mechanism (s) of bee venom as a candidate of anti-cancer drug, we examined the effects of the compound on the growth of human lung carcinoma cell line A549. Bee venom treatment declined the cell growth and viability of A549 cells in a concentration-dependent manner, which was associated with induction of apoptotic cell death. Bee venom down-regulated the levels of anti-apoptotic genes such as Bcl-2 and Bcl-XS/L, however, the levels of Bax, a pro-apoptotic gene, were up-regulated. Bee venom treatment induced not only tumor suppressor p53 but also cyclin-dependent kinase inhibitor p21WAF1/CIP1 expression in a dose-dependent manner. Furthermore, bee venom treatment induced the down-regulation of telomerase reverse transcriptase mRNA and telomeric repeat binding factor expression of A549 cells, however, the levels of telomerase-associated protein-1 and c-myc were not affected. Taken together, these findings suggest that bee venom-induced inhibition of human lung cancer cell growth is associated with the induction of apoptotic cell death via regulation of several major growth regulatory gene products, and bee venom may have therapeutic potential in human lung cancer.

• Animal cells and systems
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• v.4 no.4
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• pp.347-352
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• 2000

Programmed cell death, apoptosis, is a mechanism to maintain tissue homeostasis. Although the apoptotic process in rodent mammary tissues has been known to occur at the onset of involution, little is known about programmed cell death in the bovine tissues. Therefore, the purpose of this study was to investigate the molecular and cellular basis of apoptotic process in bovine mammary cells. Mammary tissues were obtained at different lactational and involurional stages. By apoptosis in situ endlabeling assay, apoptotic cells were found around the acinar celt lining in regressing bovine mammary tissues. The apoptosis-related genes bel-2 and bax were detected throughout involution by Northern blotting assay. The level of bax mRNA was dominantly expressed during involution. On the other hand, the bel-2 RNA transcripts were constantly expressed by 14 of post-lactation and declined thereafter. The expression of the testosterone-repressed prostate message-2 (TRPM-2) RNA transcripts, a marker for tissue remodeling, was increased as involution progressed. TNF a, were induced the DNA fragmentation and enhanced the expression of bax mRNA. In addition, milk protein secretion and amino acid uptake were decreased in mammary acinar culture treated with TNF $\alpha$. These results indicate that bovine mammary cells undergo apoptotic process after the cessation of milking and that TNF $\alpha$ may trigger apoptosis in lactating bovine mammary acini.

• The Journal of Korean Medicine
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• v.23 no.3
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• pp.74-84
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• 2002

목적 : 본 실험에서는 gerbil을 이용한 전뇌허혈 동물모델에서 뇌허혈손상 직후 지연성 뇌손상에 대한 대황의 방어효과와 Apoptosis 과정중의 Bax와 Bcl-2 단백질에 대한 조절작용을 관찰하고, TUNEL 염색법을 통하여 대황이 gerbil hippocampus CAl영역의 pyramidal neuron의 세포사에 미치는 영향과 PCl2세포를 이용한 세포배양 모델에서의 대황의 신경방어 효과를 관찰하였다. 방법 : Mongolian gerbil의 총경동맥을 5분간 폐색하여 가역성 전뇌허혈을 유발시킨 후 대황의 전탕액을 하루에 한번 경구 투여하였다. 대황의 신경 보호 효과는 수술 7일 후에 cresyl violet으로 염색하여, 살아있는 신경 세포의 수를 세어 측정하였다. 또, 수술 3일 후에는 면역조직화학적 방범을 통하여 Bax. Bcl-2단백질의 발현과 대황의 신경보호 효과와의 관련성을 알아보았다. 결과： 가역적 전뇌허혈이 일어난 동물군의 경우 hippocampus의 CAl 영역에서 살아있는 신경세포의 수는 $51.0{\pm}2.5개{\;}/mm$에 불과하였으나, 그에 비해 수술 후 7일간 대황을 투여한 동물군은 $106.2{\pm}2.5개{\;}/mm$로 살아 있는 신경세포수가 크게 증가하였다. Apoptosis를 촉진하는 단백질인 Bax의 발현은 3일간 대황을 투여한 동물군의 경우 hippocampus의 CAl 영역에서 현저하게 저해되었고, Apoptosis를 억제하는 Bcl-2 단백질의 발현은 변화가 없었다. TUNEL assay를 통하여 살펴본 결과 대황 투여군의 apoptotic 신경세포사가 감소하였으며 이는 Bax protein의 발현과 유사한 양상을 나타내었다. 결론：대황이 Bax 단백질의 발현을 억제하여 상대적으로 Bax/Bcl-2 자연적 세포사를 억제하여 Mogolian gerbil의 가역성 전뇌허혈 모델에서 신경보호효과를 나타내는 것으로 사료된다.

• Toxicological Research
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• v.17 no.3
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• pp.215-223
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• 2001

Cadmium is an ubiquitous toxic metal and chronic exposure to cadmium results in the accumulation of cadmium in the liver and kidneys. In contrast, acute exposure leads to damage mainly in the liver. Apoptosis induced by cadmium has been shown in many tissues in vivo and in cultured cells in vitro. However, the molecular mechanism of cadmium-induced apoptosis is not clear in hepatocyte. To investigate the induction of apoptosis in the hepatocyte, we used mouse hepatoma cell line, Hepalclc7 cells, and analysed the molecules that involved in cadmium-induced apoptosis. Cadmium induced the genomic DNA fragmentation, PARP cleavage, and activation of caspase-3 like protease. Caspase-9 cysteine protease was activated in a time-dependent manner but caspase-8 cysteine protease was not significantly activated in cadmium-treated Hepalclc7 cells. Cadmium also induced mitochondrial dysfunction including cytochrome c release from mitochondria, change oj mitochondrial membrane potential tranition, and tranlocation of Bax Protein into mitochondria. These results strong1y indicated that the signal Pathway of apoptotic death in cadmium-treated Hepalclc7 cells is modulated by caspase cascade via mitochondria.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.11
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• pp.4609-4615
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• 2014

Background: To investigate tumor inhibition effects and mechanisms of Angelica sinensis and Sophorae flavescentis ait decoction (ASSF) combined with diamine-dichloroplatinum (DDP). Materials and Methods: Bodyweight, tumor inhibition rate and q value were calculated for single ASSF or ASSF combined with DDP on H22 carcinoma xenograft KM mice. Biochemical methods for serum LDH, AST, ALT, and AKP, ELISA method for serum HIF-$1{\alpha}$, pathological assessemnt of thymus, immunohistochemistry detection of tumor tissue caspase3 and mutant p53 protein, and qRT-PCR detection of bax/ bcl-2 mRNA were applied. Results: Compared with DDP control group, the bodyweight increased in ASSF-DDP group (p<0.01). Tumor inhibition rates for DDP, ASSF, ASSF-DDP were 62.7%. 43.7% and 71.0% respectively, with a q value of 0.90. Compared with other groups, thymus of DDP control group had obvious pathological injury (p<0.01), serum LDH, AST, ALT, AKP increased significantly in DDP control group (p<0.01), while serum HIF-$1{\alpha}$ was increased in the model control group. Compared with this latter, the expression of mutant p53 protein and bcl-2 mRNA were decreased in all treatment groups (p<0.01), but there were no statistical difference between DDP control p and ASSF-DDP groups. The expression of caspase3 protein and bax mRNA was increased in all treatment groups, with statistical differences between the DDP and ASSF-DDP groups (p<0.01). Conclusions: ASSF can inhibit bodyweight decrease caused by DDP, can inhibit tumor growth synergistically with DDP mainly through increasing serum HIF-$1{\alpha}$ and pro-apoptotic molecules such as caspase 3 and bax, rather than through decreasing anti-apoptotic mutant p53 and bcl-2. ASSF can reduce DDP toxicity due to decreasing the release of LDH, AST, ALT, AKP into blood and enhancing thymus protection.