Horse Oil Mitigates Oxidative Damage to Human HaCaT Keratinocytes Caused by Ultraviolet B Irradiation

Piao, Mei Jing,Kang, Kyoung Ah,Zhen, Ao Xuan,Kang, Hee Kyoung,Koh, Young Sang,Kim, Bong Seok,Hyun, Jin Won MDPI 2019 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.20 No.6

<P>Horse oil products have been used in skin care for a long time in traditional medicine, but the biological effects of horse oil on the skin remain unclear. This study was conducted to evaluate the protective effect of horse oil on ultraviolet B (UVB)-induced oxidative stress in human HaCaT keratinocytes. Horse oil significantly reduced UVB-induced intracellular reactive oxygen species and intracellular oxidative damage to lipids, proteins, and DNA. Horse oil absorbed light in the UVB range of the electromagnetic spectrum and suppressed the generation of cyclobutane pyrimidine dimers, a photoproduct of UVB irradiation. Western blotting showed that horse oil increased the UVB-induced Bcl-2/Bax ratio, inhibited mitochondria-mediated apoptosis and matrix metalloproteinase expression, and altered mitogen-activated protein kinase signaling-related proteins. These effects were conferred by increased phosphorylation of extracellular signal-regulated kinase 1/2 and decreased phosphorylation of p38 and c-Jun N-terminal kinase 1/2. Additionally, horse oil reduced UVB-induced binding of activator protein 1 to the matrix metalloproteinase-1 promoter site. These results indicate that horse oil protects human HaCaT keratinocytes from UVB-induced oxidative stress by absorbing UVB radiation and removing reactive oxygen species, thereby protecting cells from structural damage and preventing cell death and aging. In conclusion, horse oil is a potential skin protectant against skin damage involving oxidative stress.</P>

Esculetin Prevents the Induction of Matrix Metalloproteinase-1 by Hydrogen Peroxide in Skin Keratinocytes

Ao Xuan Zhen,Mei Jing Piao,강경아,FERNANDO PINCHA DEVAGE SAMEERA,강희경,고영상,JIN-WON HYUN 대한암예방학회 2019 Journal of cancer prevention Vol.24 No.2

Background: Reactive oxygen species (ROS) are involved in various cellular diseases. Excessive ROS can cause intracellular oxidative stress, resulting in a calcium imbalance and even aging. In this study, we evaluated the protective effect of esculetin on oxidative stress-induced aging in human HaCaT keratinocytes. Methods: Human keratinocytes were pretreated with esculetin for 30 minutes and treated with H2O2. Then, the protective effects on oxidative stress-induced matrix metalloproteinase (MMP)-1 were detected by Flou-4-AM staining, reverse transcription-PCR, Western blotting, and quantitative fluorescence assay. Results: Esculetin prevented H2O2-induced aging by inhibiting MMP-1 mRNA, protein, and activity levels. In addition, esculetin decreased abnormal levels of phospho-MEK1, phospho-ERK1/2, phospho-SEK1, phospho-JNK1/2, c-Fos, and phospho-c-Jun and inhibited activator protein 1 binding activity. Conclusions: Esculetin prevented excessive levels of intracellular calcium and reduced the expression levels of aging-related proteins. (J Cancer Prev 2019;24:123-128)

Niacinamide Protects Skin Cells from Oxidative Stress Induced by Particulate Matter

( Ao Xuan Zhen ),( Mei Jing Piao ),( Kyoung Ah Kang ),( Pincha Devage Sameera Madushan Fernando ),( Hee Kyoung Kang ),( Young Sang Koh ),( Joo Mi Yi ),( Jin Won Hyun ) 한국응용약물학회 2019 Biomolecules & Therapeutics(구 응용약물학회지) Vol.27 No.6

Niacinamide (NIA) is a water-soluble vitamin that is widely used in the treatment of skin diseases. Moreover, NIA displays antioxidant effects and helps repair damaged DNA. Recent studies showed that particulate matter 2.5 (PM_2.5) induced reactive oxygen species (ROS), causing disruption of DNA, lipids, and protein, mitochondrial depolarization, and apoptosis of skin keratinocytes. Here, we investigated the protective effects of NIA on PM_2.5-induced oxidative stress in human HaCaT keratinocytes. We found that NIA could inhibit the ROS generation induced by PM_2.5, as well block the PM_2.5-induced oxidation of molecules, such as lipids, proteins, and DNA. Furthermore, NIA alleviated PM_2.5-induced accumulation of cellular Ca²⁺, which caused cell membrane depolarization and apoptosis, and reduced the number of apoptotic cells. Collectively, the findings show that NIA can protect keratinocytes from PM_2.5-induced oxidative stress and cell damage.

Purpurogallin Protects Keratinocytes from Damage and Apoptosis Induced by Ultraviolet B Radiation and Particulate Matter 2.5

( Ao Xuan Zhen ),( Mei Jing Piao ),( Yu Jae Hyun ),( Kyoung Ah Kang ),( Yea Seong Ryu ),( Suk Ju Cho ),( Hee Kyoung Kang ),( Young Sang Koh ),( Mee Jung Ahn ),( Tae Hoon Kim ),( Jin Won Hyun ) 한국응용약물학회 2019 Biomolecules & Therapeutics(구 응용약물학회지) Vol.27 No.4

Purpurogallin, a natural phenol obtained from oak nutgalls, has been shown to possess antioxidant, anticancer, and anti-inflammatory effects. Recently, in addition to ultraviolet B (UVB) radiation that induces cell apoptosis via oxidative stress, particulate matter 2.5 (PM_2.5) was shown to trigger excessive production of reactive oxygen species. In this study, we observed that UVB radiation and PM_2.5 severely damaged human HaCaT keratinocytes, disrupting cellular DNA, lipids, and proteins and causing mitochondrial depolarization. Purpurogallin protected HaCaT cells from apoptosis induced by UVB radiation and/or PM_2.5. Furthermore, purpurogallin effectively modulates the pro-apoptotic and anti-apoptotic proteins under UVB irradiation via caspase signaling pathways. Additionally, purpurogallin reduced apoptosis via MAPK signaling pathways, as demonstrated using MAPK-p38, ERK, and JNK inhibitors. These results indicate that purpurogallin possesses antioxidant effects and protects cells from damage and apoptosis induced by UVB radiation and PM_2.5.

Luteolin promotes apoptotic cell death via upregulation of Nrf2 expression by DNA demethylase and the interaction of Nrf2 with p53 in human colon cancer cells

강경아,Mei Jing Piao,현유재,Ao Xuan Zhen,조석주,안미정,이주미,현진원 생화학분자생물학회 2019 Experimental and molecular medicine Vol.51 No.-

Luteolin, a dietary flavone, modulates various signaling pathways involved in carcinogenesis. In this study, we investigated the molecular mechanism that underlies the apoptotic effects of luteolin mediated by DNA demethylation of the nuclear factor erythroid 2-related factor 2 (Nrf2) promoter and the interaction of Nrf2 and p53, a tumor suppressor, in human colon cancer cells. Luteolin increased the expression of apoptosis-related proteins and antioxidant enzymes. In DNA methylation, luteolin inhibited the expression of DNA methyltransferases, a transcription repressor, and increased the expression and activity of ten-eleven translocation (TET) DNA demethylases, a transcription activator. Methyl-specific polymerase chain reaction and bisulfite genomic sequencing indicated that luteolin decreased the methylation of the Nrf2 promoter region, which corresponded to the increased mRNA expression of Nrf2. In addition, luteolin increased TET1 binding to the Nrf2 promoter, as determined using a chromatin immunoprecipitation (ChIP) assay. TET1 knockdown decreased the percentages of luteolin-treated cells in sub-G1 phase and cells with fragmented nuclei. Furthermore, complex formation between p53 and Nrf2 was involved in the apoptotic effects of luteolin. These results provide insight into the mechanism that underlies the anticancer effects of luteolin on colon cancer, which involve the upregulation of Nrf2 and its interaction with the tumor suppressor.

Shikonin induces mitochondria-mediated apoptosis and attenuates epithelial-mesenchymal transition in cisplatin-resistant human ovarian cancer cells

Shilnikova, Kristina,Piao, Mei Jing,Kang, Kyoung Ah,Ryu, Yea Seong,Park, Jeong Eon,Hyun, Yu Jae,Zhen, Ao Xuan,Jeong, Yong Joo,Jung, Uhee,Kim, In Gyu,Hyun, Jin Won D.A. Spandidos 2018 Oncology letters Vol.15 No.4

<P>Cisplatin-based chemotherapy often results in the development of chemoresistance when used to treat ovarian cancer, which is difficult to overcome. The present study investigated the cytotoxic and anti-migratory effects of shikonin, a naphthoquinone compound, on cisplatin-resistant human ovarian cancer A2780 cells (A2780-CR). Shikonin had a potent dose-dependent cytotoxic effect on A2780-CR cells, with 9 µM shikonin treatment reducing A2780-CR cell viability by 50%, validate using an MTT assay. Shikonin induced apoptosis, as evidenced by the increased number of apoptotic bodies, following staining with Hoechst 33342, and terminal deoxynucleotidyl cell transferase dUTP nick end labeling-positive cells following treatment. Flow cytometry and fluorescent microscope imaging, following JC-1 staining, revealed that shikonin increased mitochondrial membrane depolarization. Also it altered the levels of apoptosis-associated proteins, leading to diminished expression of B cell lymphoma-2 (Bcl-2), enhanced expression of Bcl-associated X, and cleavage of caspase-9 and −3, as revealed using western blot analysis. Shikonin activated mitogen-activated protein kinases; while treatment with specific inhibitors of these kinases attenuated the decline in cell viability induced by shikonin treatment. In addition, the cell migration assay and western blot analysis indicated that shikonin decreased the migratory capacity of A2780-CR cells via the upregulation of epithelial-cadherin and downregulation of neural-cadherin. Taken together, the results of the present study indicated that shikonin induces mitochondria-mediated apoptosis and attenuates the epithelial-mesenchymal transition in A2780-CR cells.</P>

Shikonin Exerts Cytotoxic Effects in Human Colon Cancers by Inducing Apoptotic Cell Death via the Endoplasmic Reticulum and Mitochondria-Mediated Pathways

Xia Han,강경아,Mei Jing Piao,Ao Xuan Zhen,현유재,김현민,류예성,현진원 한국응용약물학회 2019 Biomolecules & Therapeutics(구 응용약물학회지) Vol.27 No.1

The apoptotic effects of shikonin (5,8-dihydroxy-2-[(1R)-1-hydroxy-4-methylpent-3-enyl]naphthalene-1,4-dione) on the human colon cancer cell line SNU-407 were investigated in this study. Shikonin showed dose-dependent cytotoxic activity against SNU-407 cells, with an estimated IC50 value of 3 μM after 48 h of treatment. Shikonin induced apoptosis, as evidenced by apoptotic body formation, sub-G1 phase cells, and DNA fragmentation. Shikonin induced apoptotic cell death by activating mitogen-activated protein kinase family members, and the apoptotic process was mediated by the activation of endoplasmic reticulum (ER) stress, leading to activation of the PERK/elF2α/CHOP apoptotic pathway, and mitochondrial Ca2+ accumulation. Shikonin increased mitochondrial membrane depolarization and altered the levels of apoptosis-related proteins, with a decrease in B cell lymphoma (Bcl)-2 and an increase in Bcl-2-associated X protein, and subsequently, increased expression of cleaved forms of caspase-9 and -3. Taken together, we suggest that these mechanisms, including MAPK signaling and the ER- and mitochondria-mediated pathways, may underlie shikonin-induced apoptosis related to its anticancer effect.

7,8-Dihydroxyflavone Protects High Glucose-Damaged Neuronal Cells against Oxidative Stress

조석주,강경아,Mei Jing Piao,류예성,Pincha Devage Sameera Madushan Fernando,Ao Xuan Zhen,현유재,안미정,강희경,현진원 한국응용약물학회 2019 Biomolecules & Therapeutics(구 응용약물학회지) Vol.27 No.1

Oxidative stress is considered a major contributor in the pathogenesis of diabetic neuropathy and in diabetes complications, such as nephropathy and cardiovascular diseases. Diabetic neuropathy, which is the most frequent complications of diabetes, affect sensory, motor, and autonomic nerves. This study aimed to investigate whether 7,8-dihydroxyflavone (7,8-DHF) protects SH-SY5Y neuronal cells against high glucose-induced toxicity. In the current study, we found that diabetic patients exhibited higher lipid peroxidation caused by oxidative stress than healthy subjects. 7,8-DHF exhibits superoxide anion and hydroxyl radical scavenging activities. High glucose-induced toxicity severely damaged SH-SY5Y neuronal cells, causing mitochondrial depolarization; however, 7,8-DHF recovered mitochondrial polarization. Furthermore, 7,8-DHF effectively modulated the expression of pro-apoptotic protein (Bax) and anti-apoptotic protein (Bcl-2) under high glucose, thus inhibiting the activation of caspase signaling pathways. These results indicate that 7,8-DHF has antioxidant effects and protects cells from apoptotic cell death induced by high glucose. Thus, 7,8-DHF may be developed into a promising candidate for the treatment of diabetic neuropathy.

Luteolin promotes apoptotic cell death via upregulation of Nrf2 expression by DNA demethylase and the interaction of Nrf2 with p53 in human colon cancer cells

Kang, Kyoung Ah,Piao, Mei Jing,Hyun, Yu Jae,Zhen, Ao Xuan,Cho, Suk Ju,Ahn, Mee Jung,Yi, Joo Mi,Hyun, Jin Won Nature Publishing Group UK 2019 Experimental and molecular medicine Vol.51 No.4

<▼1><P>Luteolin, a dietary flavone, modulates various signaling pathways involved in carcinogenesis. In this study, we investigated the molecular mechanism that underlies the apoptotic effects of luteolin mediated by DNA demethylation of the nuclear factor erythroid 2-related factor 2 (Nrf2) promoter and the interaction of Nrf2 and p53, a tumor suppressor, in human colon cancer cells. Luteolin increased the expression of apoptosis-related proteins and antioxidant enzymes. In DNA methylation, luteolin inhibited the expression of DNA methyltransferases, a transcription repressor, and increased the expression and activity of ten-eleven translocation (TET) DNA demethylases, a transcription activator. Methyl-specific polymerase chain reaction and bisulfite genomic sequencing indicated that luteolin decreased the methylation of the Nrf2 promoter region, which corresponded to the increased mRNA expression of Nrf2. In addition, luteolin increased TET1 binding to the Nrf2 promoter, as determined using a chromatin immunoprecipitation (ChIP) assay. TET1 knockdown decreased the percentages of luteolin-treated cells in sub-G<SUB>1</SUB> phase and cells with fragmented nuclei. Furthermore, complex formation between p53 and Nrf2 was involved in the apoptotic effects of luteolin. These results provide insight into the mechanism that underlies the anticancer effects of luteolin on colon cancer, which involve the upregulation of Nrf2 and its interaction with the tumor suppressor.</P></▼1><▼2><P><B>Cancer: Cell-killing plant compound exerts antioxidant effects</B></P><P>A molecule found in fruits, vegetables and herbs helps kill colon cancer cells by activating a master regulator of detoxifying enzymes. Jin Won Hyun from Jeju National University School of Medicine in South Korea and colleagues treated human colon cancer cells with luteolin, a molecule that occurs naturally in many food plants. They showed that luteolin increased the levels of proteins involved in cell death and antioxidant responses by causing DNA-modifying enzymes to strip suppressive chemical markers off the gene encoding Nrf2, a protein that regulates antioxidant effects. Nrf2 levels subsequently increased and the protein interacted with the tumor suppressor p53 to facilitate destruction of the colon cancer cells. The findings offer a mechanistic basis for using luteolin to help prevent and treat cancer.</P></▼2>

Luteolin induces apoptotic cell death via antioxidant activity in human colon cancer cells

Kang, Kyoung Ah,Piao, Mei Jing,Ryu, Yea Seong,Hyun, Yu Jae,Park, Jeong Eon,Shilnikova, Kristina,Zhen, Ao Xuan,Kang, Hee Kyoung,Koh, Young Sang,Jeong, Yong Joo,Hyun, Jin Won Spandidos Publications 2017 International journal of oncology Vol.51 No.4

<P>The present study determined whether luteolin induces HT-29 colon cancer cell death through an antioxidant effect such as the activation of antioxidant enzymes. Luteolin decreased cell viability in human colon cancer cells (HT-29), whereas it had no effect on normal colon cells (FHC). Luteolin induced apoptosis by activating the mitochondria-mediated caspase pathway in HT-29 cells. Luteolin caused loss of the mitochondrial membrane action potential, increased mitochondrial Ca2+ level, upregulated Bax, downregulated Bcl-2, induced the release of cytochrome c from mitochondria to the cytosol, and increased the levels of the active forms of caspase-9 and caspase-3. Luteolin-induced apoptosis was accompanied by the activation of intracellular and mitochondrial reactive oxygen species scavenging through the activation of antioxidant enzymes, such as superoxide dismutase and catalase in HT-29 cells. Luteolin increased the level of reduced glutathione (GSH) and the expression of GSH synthetase, which catalyzes the second step of GSH biosynthesis. The apoptotic effect of luteolin was mediated by the activation of the mitogen-activated protein kinase signaling pathway. The present results indicate that luteolin induces apoptosis by promoting antioxidant activity and activating MAPK signaling in human colon cancer cells.</P>