• Korean Journal of Organic Agriculture
• /
• v.19 no.2
• /
• pp.245-253
• /
• 2011

This study was carried out to investigate the biological effects of organic soybean extracts. Cellular and molecular analysis was performed to determine anti-oxidative, anti-inflammatory, anti-apoptotic, and anti-inflammatory effects of soybean extracts. First, we obtained various solvent extracts of soybean such as water, ethanol, and methanol. Molecular and cellular analysis were performed with 0.1 mg/ml concentration of each solvent extracts. The results of anti-oxidative, antiinflammatory and anti-apoptotic effects of organic soybean extracts were prominent. However, organic soybean extracts were not observed in anti-allergic effects determined by releasing histamine from rat mast cell line, RBL-2H3. Conclusively, organic soybean suppress inflammatory responses. In addition, organic soybean could be applied as a functional food ingredient for treatment of chronic inflammation, asthma, and atopic dermatitis with enhanced anti-inflammatory activities.

• Journal of Life Science
• /
• v.26 no.9
• /
• pp.1015-1021
• /
• 2016

5-fluorouracil (5-FU), a pyrimidine analog, is a widely used anticancer drug, which works through irreversible inhibition of thymidylate synthase. In the present study, it was investigated the anti-proliferative effects and molecular mechanisms of 5-FU using Ewing's Sarcoma CHP-100 Cells. The present data indicated that treatment of 5-FU to CHP-100 cells induced a G1 phase arrest of the cell cycle in a time-dependent manner. 5-FU-induced G1 arrest was correlated with the accumulation of the hypophosphorylated form of the retinoblastoma protein (pRB) and association of pRB with the transcription factors E2F-1 and E2F-4. Although 5-FU treatment did affect the levels of cyclin-dependent kinases, the levels of cyclin A and B were markedly down-regulated as compared with the untreated control group. In addition, 5-FU-induced G1 arrest of CHP-100 cells was also associated with the induction of apoptosis, as determined by apoptotic cell morphologies, degradation of poly(ADP-ribose) polymerase and Annexin V staining. Furthermore, 5-FU induced the loss of mitochondrial membrane potential with up-regulated pro-apoptotic Bax expression, down-regulated anti-apoptotic Bcl-2 expression and cytochrome c release from mitochondria to cytosol. Collectively, the data suggest that 5-FU is effective in inducing cell growth reduction and apoptosis, in part, by reducing phosphorylation of pRB and activating mitochondrial dysfunction in CHP-100 cells.

• Herbal Formula Science
• /
• v.13 no.1
• /
• pp.35-48
• /
• 2005

Alzheimer's disease(AD) is a geriatric dementia that is widespread in old age. In the near future AD will be the biggest problem in public health service. It has been widely believed that $A{\beta}$ peptide devided from APP causes apoptotic neurotoxicity in brain. However, recent evidence suggests that n99 may be an important factor causing neurotoxicity in AD. Mouse PC12 cells expressed with n99 exhibited remarkable apoptotic cell damage. We invesgated the protective effects of Gagamgobonhwan water extract(GKG). Findings from our experiments have shown that GKG inhibits the activities of CT99, which has neurotoxicities and apoptotic activities in cell line. In addition, treatment of GKG($75{\mu}g/ml$ 24 hours) partially prevented CT99-induced cytotoxicity in PC12 cells. As the result of this study, in GKG group the apoptosis in the nervous system was inhibited, the repair against the degerneration of PC12 cells by CT99 expression is promoted. Taken together, GKG exhibited inhibition of CT99-induced apoptotic cell death. GKG may be beneficial for the treatment of AD.

• The Korean Journal of Physiology and Pharmacology
• /
• v.21 no.6
• /
• pp.599-607
• /
• 2017

Most normal cells express L-type amino acid transporter 2 (LAT2). However, L-type amino acid transporter 1 (LAT1) is highly expressed in many tumor cells and presumed to support their increased growth and proliferation. This study examined the effects of JPH203, a selective LAT1 inhibitor, on cell growth and its mechanism for cell death in Saos2 human osteosarcoma cells. FOB human osteoblastic cells and Saos2 cells expressed LAT1 and LAT2 together with their associating protein 4F2 heavy chain, but the expression of LAT2 in the Saos2 cells was especially weak. JPH203 and BCH, a non-selective L-type amino acid transporter inhibitor, potently inhibited L-leucine uptake in Saos2 cells. As expected, the intrinsic ability of JPH203 to inhibit L-leucine uptake was far more efficient than that of BCH in Saos2 cells. Likewise, JPH203 and BCH inhibited Saos2 cell growth with JPH203 being superior to BCH in this regard. Furthermore, JPH203 increased apoptosis rates and formed DNA ladder in Saos2 cells. Moreover, JPH203 activated the mitochondria-dependent apoptotic signaling pathway by upregulating pro-apoptotic factors, such as Bad, Bax, and Bak, and the active form of caspase-9, and downregulating anti-apoptotic factors, such as Bcl-2 and Bcl-xL. These results suggest that the inhibition of LAT1 activity via JPH203, which may act as a potential novel anti-cancer agent, leads to apoptosis mediated by the mitochondria-dependent intrinsic apoptotic signaling pathway by inducing the intracellular depletion of neutral amino acids essential for cell growth in Saos2 human osteosarcoma cells.

• Molecules and Cells
• /
• v.38 no.2
• /
• pp.145-150
• /
• 2015

Continuous intra- and extracellular stresses induce disorder of $Ca^{2+}$ homeostasis and accumulation of unfolded protein in the endoplasmic reticulum (ER), which results in ER stress. Severe long-term ER stress triggers apoptosis signaling pathways, resulting in cell death. Neural epidermal growth factor-like like protein 2 (NELL2) has been reported to be important in protection of cells from cell death-inducing environments. In this study, we investigated the cytoprotective effect of NELL2 in the context of ER stress induced by thapsigargin, a strong ER stress inducer, in Cos7 cells. Overexpression of NELL2 prevented ER stress-mediated apoptosis by decreasing expression of ER stress-induced C/EBP homologous protein (CHOP) and increasing ER chaperones. In this context, expression of anti-apoptotic Bcl-xL was increased by NELL2, whereas NELL2 decreased expression of pro-apoptotic proteins, such as cleaved caspases 3 and 7. This anti-apoptotic effect of NELL2 is likely mediated by extracellular signal-regulated kinase (ERK) signaling, because its inhibitor, U0126, inhibited effects of NELL2 on the expression of anti- and pro-apoptotic proteins and on the protection from ER stress-induced cell death.

• Biomolecules & Therapeutics
• /
• v.32 no.3
• /
• pp.267-280
• /
• 2024

Apoptosis, programmed cell death pathway, is a vital physiological mechanism that ensures cellular homeostasis and overall cellular well-being. In the context of cancer, where evasion of apoptosis is a hallmark, the overexpression of anti-apoptotic proteins like Bcl2, Bcl-xL and Mcl-1 has been documented. Consequently, these proteins have emerged as promising targets for therapeutic interventions. The BCL-2 protein family is central to apoptosis and plays a significant importance in determining cellular fate serving as a critical determinant in this biological process. This review offers a comprehensive exploration of the BCL-2 protein family, emphasizing its dual nature. Specifically, certain members of this family promote cell survival (known as anti-apoptotic proteins), while others are involved in facilitating cell death (referred to as pro-apoptotic and BH3-only proteins). The potential of directly targeting these proteins is examined, particularly due to their involvement in conferring resistance to traditional cancer therapies. The effectiveness of such targeting strategies is also discussed, considering the tumor's propensity for anti-apoptotic pathways. Furthermore, the review highlights emerging research on combination therapies, where BCL-2 inhibitors are used synergistically with other treatments to enhance therapeutic outcomes. By understanding and manipulating the BCL-2 family and its associated pathways, we open doors to innovative and more effective cancer treatments, offering hope for resistant and aggressive cases.

• 대한두경부종양학회:학술대회논문집
• /
• 2001.11a
• /
• pp.248-248
• /
• 2001

• Journal of Marine Bioscience and Biotechnology
• /
• v.1 no.2
• /
• pp.63-70
• /
• 2006

Natural product compounds are the source of numerous therapeutic agents. The marine environment produces natural products from a variety of structural classes exhibiting activity against numerous disease targets including anticancer agents. Among these, pectenotoxin-2 (PTX-2), which was first identified as a cytotoxic entity in marine sponges, which depolymerizes actin filaments, was found to be highly effective and more potent to activate an intrinsic pathway of apoptosis in p53-deficient tumor cells compared to those with functional p53 both in vitro and in vivo. However, the anti-proliferative mechanism of the compound at non-cytotoxic concentrations has not yet been explored. In the current study, we sought to investigate anti-proliferation and apoptosis of PTX-2 against U937 human leukemic cells and its underlying molecular mechanism. Exposure of U937 cells to PTX-2 resulted in growth inhibition and induction of apoptosis in dose- and time-dependent manner as measured by MTT assay, fluorescent microscopy and flow cytometric analysis. The anti-proliferative effect of PTX-2 was associated with a marked increase in the expression of cyclin-dependent kinase p21 (WAF1/CIP1) mRNA which was tumor suppressor p53-independent. The increase in apoptosis was connected with a time-dependent down-regulation of anti-apoptotic Bcl-XL and inhibitor of apoptosis proteins (IAPs) family such as XIAP and cIAP-2. Though additional studies are needed, these findings suggested that PTX-2-induced inhibition of U937 cells was associated with the induction of apoptotic cell death and the results provided important new insights into the possible molecular mechanisms of the anti-cancer activity of PTX-2.

• BMB Reports
• /
• v.34 no.5
• /
• pp.391-394
• /
• 2001

The balance between life and death of a cell regulates essential developmental processes in multicellular organisms. Apoptotic cell death is a complex, stepwise program involving multiple protein components that trigger and execute the demise of the cell. Of the many triggers of apoptosis, most are not well understood, but some key components have been identified, such as those of the Bcl-2 family, which function as anti-apoptotic or proapoptotic factors. Bax, a pro-apoptotic member of this family, has been shown to serve as a component of many apoptotic triggering cascades and its mechanism of action is the focus of intense study. Herein we discuss current, differing ideas on the function of Bax and its structure, and suggest novel mechanisms for how this death protein targets mitochondria, triggering apoptosis.

• Proceedings of the Korean Society for Applied Microbiology Conference
• /
• 2004.06a
• /
• pp.297-301
• /
• 2004

The purpose of the present study was to investigate the anti-proliferative and apoptotic effects of MCS-C2, a novel analogue of toyocamycin and sangivamycin, in human promyelocytic leukemia (HL-60) cells. When treated with MCS-C2, inhibited proliferation associated with cell cycle arrest and apoptotic induction was found in the HL-60 cells in a concentration-dependent and time-dependent manner. This apoptotic induction was associated with the cleavage of Bid and a release of cytochrome c from mitochondria into the cytosol, followed by the activation of caspase-3 and inactivation of poly (ADP-ribose) polymerase (PARP). However, there was no significant change in any other mitochondrial membrane proteins, such as Bcl-2 and Bax. Consequently, the current findings suggest that the mitochondrial pathway was primarily involved in the MCS-C2-induced apoptosis in the human promyelocytic leukemia HL-60 cells.