• Asian Pacific Journal of Cancer Prevention
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• v.14 no.7
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• pp.4267-4271
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• 2013

Background: As natural medicines in Asia, curcumin and triptolide extracted from different drug plants have proven to possess anticancer potential and widely used for anti-cancer research. The present study attempted to clarify that curcumin and triptolide synergistically suppress ovarian cancer cell growth in vitro. Methods: To test synergic effects, cell viability and apoptosis were analyzed after curcumin and triptolide combination treatment on ovarian cancer cell lines. Synergistic effects on apoptosis induction were determined by lactate dehydrogenase (LDH) leakage assay, intracellular reactive oxygen species (ROS) assay, mitochondrial membrane potential (MMP) loss assay and flow cytometry analysis. Critical regulators of cell proliferation and apoptosis related were analyzed by qRT-PCR and Western blotting. Results: We showed that the combination of curcumin and triptolide could synergistically inhibit ovarian cancer cell growth, and induce apoptosis, which is accompanied by HSP27 and HSP70, indicating that HSP27 and HSP70 play the important role in the synergic effect. Conclusions: From the result present here, curcumin and triptolide combination with lower concentration have a synergistic anti-tumor effect on ovarian cancer and which will have a good potential in clinical applications.

• Herbal Formula Science
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• v.29 no.4
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• pp.277-283
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• 2021

Objectives : We investigated the effects of Bojungikgi-tang (BJIGT) on P450 cytochrome enzyme and oxidative stress in the cells. Methods : We enrolled the HepG2 hepatocyte cell line to assess MTT assay, flow cytometer, and immunoblotting analysis. Expression of CYP450 was confirmed by immunoblotting analysis in the Huh7 cell line. Results : We determined that BJIKT markdely changed the expression of the CYP2C19, CYP2D6, and CYP2E1. Moreover, BJIKT inhibited the cell toxicity induced by arachidonic acid + iron treatment, as assessed by FACS analysis. BJIKT induced AMPK activation, which increased the phophorylation of ACC. Conclusions : This study verified the effects of BJIKT, on P450, ROS production, mitochondrial damage and AMPK signaling pathway, which might give us the scientific information about the traditional herbal prescription.

• Korean Journal of Exercise Nutrition
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• v.24 no.3
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• pp.32-38
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• 2020

[Purpose] Sarcopenia is considered one of the major causes of disability in the elderly population and is highly associated with aging. Exercise is an essential strategy for improving muscle health while aging and involves multiple metabolic and transcriptional adaptations. Although the beneficial effects of exercise modalities on skeletal muscle structure and function in aging are well recognized, the exact cellular and molecular mechanisms underlying the influence of exercise have not been fully elucidated. [Methods] We summarize the biochemical pathways involved in the progression and pathogenesis of sarcopenia and describe the beneficial effects of exercise training on the relevant signaling pathways associated with sarcopenia. [Results] This study briefly introduces current knowledge on the signaling pathways involved in the development of sarcopenia, effects of aerobic exercise on mitochondria-related parameters and mitochondrial function, and role of resistance exercise in the regulation of muscle protein synthesis against sarcopenia. [Conclusion] This review suggested that the beneficial effects of exercise are still under-explored, and accelerated research will help develop better modalities for the prevention, management, and treatment of sarcopenia.

• Journal of Microbiology and Biotechnology
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• v.33 no.1
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• pp.135-141
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• 2023

Protection of skin cells from chronic infrared-A (IRA) irradiation is crucial for anti-photoaging of the skin. In this study, we investigated the protective activity of Rg3(S) and Rg3(S)-incorporated anionic soybean lecithin liposomes (Rg3/Lipo) with a size of approximately 150 nm against IRA-induced photodamage in human fibroblasts. The formulated Rg3/Lipo showed increased solubility in aqueous solution up to a concentration of 200 ㎍/ml, compared to free Rg3(S). In addition, Rg3/Lipo exhibited superior colloidal stability in aqueous solutions and biocompatibility for normal human dermal fibroblasts (NHDFs). After repeated IRA irradiation on NHDFs, elevated levels of cellular and mitochondrial reactive oxygen species (ROS) were greatly reduced by Rg3(S) and Rg3/Lipo. In addition, cells treated with Rg3/Lipo exhibited noticeably reduced apoptotic signals following IRA irradiation compared to untreated cells. Thus, considering aqueous solubility and cellular responses, Rg3/Lipo could serve as a promising infrared protector for healthy aging of skin cells.

• Journal of Nutrition and Health
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• v.51 no.6
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• pp.498-506
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• 2018

Purpose: Lycopene, a carotenoid with anti-oxidant properties, occurs naturally in tomatoes and pink grapefruit. Although the beneficial effects of lycopene on various disorders have been established, little attention has been paid to the possible anti-diabetic effects of lycopene focusing on ${\beta}$-cells. Therefore, this study investigated the potential of lycopene to protect ${\beta}$-cells against apoptosis induced by a cytokine mixture. Methods: For toxicity experiments, the cells were treated with 0.1 ~ 10 nM of lycopene, and the cell viability in INS-1 cells (a rat ${\beta}$-cell line) was measured using a MTT assay. To induce cytokine toxicity, the cells were treated with a cytokine mixture (20 ng/mL of $TNF{\alpha}$ + 20 ng/mL of IL-$1{\beta}$) for 24 h, and the effects of lycopene (0.1 nM) on the cytokine toxicity were measured using the MTT assay. The expression levels of the apoptotic proteins were analyzed by Western blotting, and the level of intracellular reactive oxidative stress (ROS) was monitored using a DCFDA fluorescent probe. The intracellular ATP levels were determined using a luminescence kit, and mRNA expression of the genes coding for anti-oxidative stress response and mitochondrial function were analyzed by quantitative reverse-transcriptase PCR. Results: Exposure of INS-1 cells to 0.1 nM of lycopene increased the cell viability significantly, and protected the cells from cytokine-induced death. Lycopene upregulated the mRNA and protein expression of B-cell lymphoma-2 (Bcl-2) and reduced the expression of the Bcl-2 associated X (Bax) protein. Lycopene inhibited apoptotic signaling via a reduction of the ROS, and this effect correlated with the upregulation of anti-oxidative stress response genes, such as GCLC, NQO1, and HO-1. Lycopene increased the mRNA expression of mitochondrial function-related genes and increased the cellular ATP level. Conclusion: These results suggest that lycopene reduces the level of oxidative stress and improves the mitochondrial function, contributing to the prevention of cytokine-induced ${\beta}$-cell apoptosis. Therefore, lycopene could potentially serve as a preventive and therapeutic agent for the treatment of type 2 diabetes.

• Biomolecules & Therapeutics
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• v.31 no.4
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• pp.446-455
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• 2023

The mechanistic functions of 3-deoxysappanchalcone (3-DSC), a chalcone compound known to have many pharmacological effects on lung cancer, have not yet been elucidated. In this study, we identified the comprehensive anti-cancer mechanism of 3-DSC, which targets EGFR and MET kinase in drug-resistant lung cancer cells. 3-DSC directly targets both EGFR and MET, thereby inhibiting the growth of drug-resistant lung cancer cells. Mechanistically, 3-DSC induced cell cycle arrest by modulating cell cycle regulatory proteins, including cyclin B1, cdc2, and p27. In addition, concomitant EGFR downstream signaling proteins such as MET, AKT, and ERK were affected by 3-DSC and contributed to the inhibition of cancer cell growth. Furthermore, our results show that 3-DSC increased redox homeostasis disruption, ER stress, mitochondrial depolarization, and caspase activation in gefitinib-resistant lung cancer cells, thereby abrogating cancer cell growth. 3-DSC induced apoptotic cell death which is regulated by Mcl-1, Bax, Apaf-1, and PARP in gefitinib-resistant lung cancer cells. 3-DSC also initiated the activation of caspases, and the pan-caspase inhibitor, Z-VAD-FMK, abrogated 3-DSC induced-apoptosis in lung cancer cells. These data imply that 3-DSC mainly increased mitochondria-associated intrinsic apoptosis in lung cancer cells to reduce lung cancer cell growth. Overall, 3-DSC inhibited the growth of drug-resistant lung cancer cells by simultaneously targeting EGFR and MET, which exerted anti-cancer effects through cell cycle arrest, mitochondrial homeostasis collapse, and increased ROS generation, eventually triggering anti-cancer mechanisms. 3-DSC could potentially be used as an effective anti-cancer strategy to overcome EGFR and MET target drug-resistant lung cancer.

• Journal of Microbiology and Biotechnology
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• v.33 no.5
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• pp.591-599
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• 2023

Fisetin is a bioactive flavonol molecule and has been shown to have antioxidant potential, but its efficacy has not been fully validated. The aim of the present study was to investigate the protective efficacy of fisetin on C2C12 murine myoblastjdusts under hydrogen peroxide (H₂O₂)-induced oxidative damage. The results revealed that fisetin significantly weakened H₂O₂-induced cell viability inhibition and DNA damage while blocking reactive oxygen species (ROS) generation. Fisetin also significantly alleviated cell cycle arrest by H₂O₂ treatment through by reversing the upregulation of p21WAF1/CIP1 expression and the downregulation of cyclin A and B levels. In addition, fisetin significantly blocked apoptosis induced by H₂O₂ through increasing the Bcl-2/Bax ratio and attenuating mitochondrial damage, which was accompanied by inactivation of caspase-3 and suppression of poly(ADP-ribose) polymerase cleavage. Furthermore, fisetin-induced nuclear translocation and phosphorylation of Nrf2 were related to the increased expression and activation of heme oxygenase-1 (HO-1) in H₂O₂-stimulated C2C12 myoblasts. However, the protective efficacy of fisetin on H₂O₂-mediated cytotoxicity, including cell cycle arrest, apoptosis and mitochondrial dysfunction, were greatly offset when HO-1 activity was artificially inhibited. Therefore, our results indicate that fisetin as an Nrf2 activator effectively abrogated oxidative stress-mediated damage in C2C12 myoblasts.

• Asian-Australasian Journal of Animal Sciences
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• v.27 no.5
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• pp.635-647
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• 2014

Unfertilized oocytes age inevitably after ovulation, which limits their fertilizable life span and embryonic development. Rapamycin affects mammalian target of rapamycin (mTOR) expression and cytoskeleton reorganization during oocyte meiotic maturation. The goal of this study was to examine the effects of rapamycin treatment on aged porcine oocytes and their in vitro development. Rapamycin treatment of aged oocytes for 24 h (68 h in vitro maturation [IVM]; $44h+10{\mu}M$ rapamycin/24 h, $47.52{\pm}5.68$) or control oocytes (44 h IVM; $42.14{\pm}4.40$) significantly increased the development rate and total cell number compared with untreated aged oocytes (68 h IVM, $22.04{\pm}5.68$) (p<0.05). Rapamycin treatment of aged IVM oocytes for 24 h also rescued aberrant spindle organization and chromosomal misalignment, blocked the decrease in the level of phosphorylated-p44/42 mitogen-activated protein kinase (MAPK), and increased the mRNA expression of cytoplasmic maturation factor genes (MOS, BMP15, GDF9, and CCNB1) compared with untreated, 24 h-aged IVM oocytes (p<0.05). Furthermore, rapamycin treatment of aged oocytes decreased reactive oxygen species (ROS) activity and DNA fragmentation (p<0.05), and downregulated the mRNA expression of mTOR compared with control or untreated aged oocytes. By contrast, rapamycin treatment of aged oocytes increased mitochondrial localization (p<0.05) and upregulated the mRNA expression of autophagy (BECN1, ATG7, MAP1LC3B, ATG12, GABARAP, and GABARAPL1), anti-apoptosis (BCL2L1 and BIRC5; p<0.05), and development (NANOG and SOX2; p<0.05) genes, but it did not affect the mRNA expression of pro-apoptosis genes (FAS and CASP3) compared with the control. This study demonstrates that rapamycin treatment can rescue the poor developmental capacity of aged porcine oocytes.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2018.10a
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• pp.103-103
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• 2018

Oenothera biennis, commonly known as evening primrose, a potential source of natural bioactive substances: flavonoids, steroids, tannins, fatty acids and terpenoids responsible for a diverse range of pharmacological functions. However, whether extract prepared from aerial part of O. biennis (APOB) protects skin against oxidative stress remains unknown. To investigate the protective effects of APOB against oxidative stress-induced cellular damage and elucidated the underlying mechanisms in the HaCaT human skin keratinocytes. Our results revealed that treatment with APOB prior to hydrogen peroxide ($H_2O_2$) exposure significantly increased viability, and the highest DPPH radical-scavenging activities and reducing power of HaCaT cells. APOB also effectively attenuated H2O2-induced comet tail formation and inhibited the $H_2O_2$-induced phosphorylation levels of the histone ${\gamma}H2AX$, as well as the number of apoptotic bodies and Annexin V-positive cells. In addition, APOB exhibited scavenging activity against intracellular reactive oxygen species (ROS) accumulation and restored the mitochondrial membrane potential loss by $H_2O_2$. Moreover, $H_2O_2$ enhanced the cleavage of caspase-3 and degradation of poly (ADP-ribose)-polymerase (PARP), a typical substrate protein of activated caspase-3, as well as DNA fragmentation; however, these events were almost totally reversed by pretreatment with APOB. Furthermore, APOB increased the levels of heme oxygenase-1 (HO-1), which is a potent antioxidant enzyme, associated with the induction of nuclear factor-erythroid 2-related factor 2 (Nrf2). According to our data, APOB is able to protect HaCaT cells from $H_2O_2$-induced DNA damage and cell death through blocking cellular damage related to oxidative stress through a mechanism that would affect ROS elimination and activating the Nri2/HO-1 signaling pathway.

• Journal of Physiology & Pathology in Korean Medicine
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• v.31 no.6
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• pp.374-379
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• 2017

Hair loss affects interpersonal relationships and causes psychological stress. In this study, we investigated the antioxidant activity of Cynanchi Wilfordii Radix (CWR) and its effects on dermal papilla (DP) cells. Antioxidant efficacy was examined by ABTS assay. To confirm the effect on cell activity, MTS assay was performed and cell count was directly measured by hemocytometer. The mRNA expression of genes involved in hair formation and hair loss formation was confirmed by quantitative RT-PCR. CWR has a strong antioxidant activity. Cell viability of DP cells was increased to 118.5% by treatment of 0.5 mg/ml CWR for 24 hours, but the effect on the cell number was insignificant. These results suggest that CWR increases mitochondrial activity without promoting cell proliferation. Treatment of DP cells with 0.5 mg/ml CWR resulted in 48.5% reduction of mRNA expression of type 2 $5{\alpha}$-reductase, a major cause of male hair loss. In addition, mRNA expression of bone morphogenetic pretein (BMP), fibroblast growth factor (FGF)7, and FGF10, which are closely related to hair growth, was also decreased. Reactive oxygen species (ROS) acts as a cause of hair loss. The excellent antioxidant efficacy of CWR is thought to be able to effectively remove ROS. The dihydrotestosterone produced by type 2 $5{\alpha}$-reductase in DP cells is a potent inducer of male pattern hair loss. The inhibitory effect of type 2 $5{\alpha}$-reductase mRNA on DP cells induced by CWR may induce a positive therapeutic effect of male pattern hair loss.