• 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.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.11
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• pp.4893-4898
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• 2016

Objective: To investigate the impact of a Croton tiglium extract on cellular proliferation and apoptosis in a non-small cell lung cancer cell line (A549) in vitro. Methods: A Croton tiglium seed methanol extract was prepare and assessed for effects on A549 cells regarding cellular proliferation, apoptotic rates, and expression of apoptosis related genes and proteins using real-time PCR and immunofluorescence. Results: The tested Croton tiglium extract inhibited A549 cell proliferation in a dose- and time-dependent manner, with significant elevation of apoptotic indexes at various concentrations after 24 h. In addition, rates in both early and late stages were higher in treated than untreated groups, the $100{\mu}g/ml$ dose causing the highest levels of apoptosis. RT-PCR showed that A549 cells treated with $100{\mu}g/ml$ Croton tiglium extract for 24 h has markedly higher Bax mRNA expression levels and obviously lower Bcl-2 expression levels than controls, equivalent results being observed for proteins by immunofluorescence. However, the mRNA expression levels of Fas and caspase-8 were not significantly altered. Conclusion: A Croton tiglium extract can inhibit proliferation of A549 cells and promote apoptosis though Bax/Bcl-2 pathways.

• Toxicological Research
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• v.19 no.1
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• pp.67-72
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• 2003

Cholestatic liver injury results from the accumulation of toxic bile salts within the liver. The aim of the present study is to elucidate the changes in expression and cellular localization of apoptosis related proteins in the liver of bile duct-ligated (BDL) rat. Extrahepatic cholestasis was induced by double ligation of the common bile duct and cut between the ligatures. Animals were sacrificed at day 3 and at week 1, 2, 4, 6, and 8 after BDL. The number of TUNEL positive cells was increased significantly after 3 days of BDL, decreased over 2 weeks and remained constant thereafter. Fas expression was not changed and activation of caspase 8 did not occur. Fas immunoreactivity was exclusively observed in the cytoplasm of hepatocytes, indicating that Fas expressed in rat hepatocytes is a soluble form. Hepatocyte apoptosis was associated with Bax expression, which showed a peak at day 3 and decreased over time gradually. Immnunostaining of Bax was observed in hepatocytes and bile duct epithelial cells (BEC) of control and BDL rats. Bcl-2 was increased over time in BDL rats. These results suggest that apoptosis of hepatocytes in BDL rats is independent of Fas and controlled by Bax expression.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6739-6742
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• 2013

Background: Breast cancer is a major health problem worldwide. Olive oil induces apoptosis in some cancer cells due to phenolic compounds like oleuropein. Although oleuropein has anticancer activity, the underlying mechanisms of action remain unknown. The study aimed to assess the mechanism of oleuropin-induced breast cancer cell apoptosis. Materials and Methods: p53, Bcl-2 and Bax gene expression was evaluated by semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) in luminal MCF-7 cells. Results: Oleuropein-induced apoptosis was accompanied by up-regulation of both p53 and Bax gene expression levels and down-regulation in Bcl2. Conclusions: Oleuropein induces apoptosis in breast tumour cells via a p53-dependent pathway mediated by Bax and Bcl2 genes. Therefore, oleuropein may have therapeutic potential in breast cancer patients by inducing apoptosis via activation of the p53 pathway.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.2095-2100
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• 2012

Sulforaphane (SFN) an isothiocyanate formed by hydrolysis of glucosinolates found in Brassica oleraceae is reported to possess anticancer and antioxidant activities. In this study, we isolated SFN from red cabbage (Brassica oleraceae var rubra) and evaluated the comparative antiproliferative activity of various fractions (standard SFN, extract and purified SFN) by MTT assay in human epithelial carcinoma HEp -2 and and Vero cells. Probable apoptotic mechanisms mediated through p53, bax and bcl-2 were also examined. The SFN fraction was collected by HPLC, enriched for its SFN content and confirmed. Expression of apoptosis-related proteins was detected by western blotting and RT PCR. Results showed that Std SFN and purified SFN concentration found to have closer $IC_{50}$ which is equal to 58.96 microgram/ml (HEp-2 cells), 61.2 microgram/ml (Vero cells) and less than the extract which is found to be 113 microgram/ml (HEp-2 cells) and 125 microgram/ml (Vero cells). Further studies on apoptotic mechanisms showed that purified SFN down-regulated the expression of bcl-2 (antiapoptotic), while up-regulating p53 and Bax (proapoptotic) proteins, as well as caspase-3. This study indicates that purified SFN possesses antiproliferative effects the same as Std SFN and its apoptotic mechanism in HEp-2 cells could be mediated through p53 induction, bax and bcl-2 signaling pathways.

• Archives of Pharmacal Research
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• v.22 no.5
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• pp.448-453
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• 1999

In ginsenoside Rh2-treated rat glioma C6Bu-1 cells, apoptotic morphological changes, such as cell shrinkage, chromatin condensation and pyknosis were confirmed by means of electron microscopy. To evaluate whether induction of apoptosis by ginsenoside Rh2 is mediated by the members of Bcl-2 family, we first established C6Bu-1 cells overexpressing Bcl-2. It was demonstrated that the expression of Bcl-2, Bcl-xL, and Bax was not altered in ginsenoside Rh2-treated C6Bu-1 overexpressing C6Bu-1 cells failed to prevent from ginsenoside Rh2-induced cell death. These results suggest the existence of other apoptotic pathway that requires induction of apoptosis by ginsenoside Rh2 rather than the pathway through Bcl-2, $Bcl-x_{L}$ or Bax in C6Bu-1 cells.

• 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.

• Journal of the Korean Ceramic Society
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• v.36 no.3
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• pp.325-331
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• 1999

SrWO4가 첨가된 (Sr1-xBax)(Mg1/3Nb2/3)O3의 마이크로파 유전특성에 관하여 조사하였다. 관찰된 조성영역에서 Sr(Mg1/3Nb2/3)O3과 Ba(Mg1/3Nb2/3)O3은 (Sr1-xBax)(Mg1/3Nb2/3)O3고용체를 형성하고 SrWO4의 첨가는 고용체의 소결성을 향상시켜 소결온도 155$0^{\circ}C$에서 상대밀도 97% 이상을 얻었다. 소결한 시편의 EDS분석결과, SrWO4의 첨가량이 많은 시편에서 2차상이 존재하는 것을 알수 있었다. 순수한 Sr(Mg1/3Nb2/3)O3에 SrWO4를 0.01 mole첨가하여 1550~1$600^{\circ}C$에서 소결한 시편의 유전특성은 $\varepsilon$r 30, Q$\times$fo$\geq$55000,$ au$f -23 ppm/$^{\circ}C$이었다. 0.01 mole SrWO4가 첨가된 (Sr1-xBax)(Mg1/3Nb2/3)O3 고용체의 유전율과 온도계숙가 x에 따라 점차적으로 계속 증가하였고 Q$\times$fo는 x$\leq$0.25에서 x에 따라 감소하고 x$\geq$0.3에서 다시 증가하였다. (Sr0.65Ba0.35)(Mg1/3Nb2/3)O3+0.01SrWO4의 조성을 갖는 시편에서 $\varepsilon$r 34.4, Q$\times$fo$\geq$55000,$\tau$f 0 ppm/$^{\circ}C$이었다.

• Journal of Acupuncture Research
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• v.18 no.3
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• pp.134-142
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• 2001

목적 : 인진(茵蔯)이 SK-N-MC 신경아세포주에서 에탄올에 의해 유발된 아폽토시스에 대한 보호작용의 기전을 연구하였다. 방법 : SK-N-MC cell line에서의 세포 보호 기전을 알아보기 위하여 reverse transcription polymerase chain reaction (RT-PCR) 기법을 이용하여 bcl-2, bax 및 caspase-3의 변화를 관찰하였다. 결과 : RT-PCR을 이용하여 분석한 결과 SK-N-MC neuroblastoma에서 에탄올 처치는 bax, bcl-2 및 caspase-3 mRNA의 발현을 증가시켰다. 인진액의 전처치후 에탄올 처치한 신경 아세포에서는 에탄올에 의해서 증가된 bax와 caspase-3 mRNA 발현이 억제되었으나, bcl-2의 발현에는 유의한 증가를 나타내지 않았다. 결론 : 이상의 결과를 통하여 에탄올에 의해서 유발된 신경아세포의 아폽토시스에서 인진이 세포보호 효과가 있음이 확인되었고 그 기전은 bax와 caspase-3의 억제에 기인할 가능성을 시사한다고 할 수 있다.

• Current Research on Agriculture and Life Sciences
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• v.29
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• pp.37-42
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• 2011

The plant-homologue of Bax Inhibitor, a gene described to suppress the cell death induced by Bax gene expression in yeast, was isolated from rice (Oryza sativa L.). Nucleic acid sequence and amino acid sequence were 741 bp and 247 bp, respectively. The amino acid sequence of the predicted protein was well conserved in plant (84 % in amino acids) and contained five membrane-spanning segments.