Effects of kojic acid, arbutin and vitamin C on cell viability and melanin synthesis in B16BL6 cells

( Yumi Park ),( Jongsung Lee ),( Junho Park ),( Deokhoon Park ) 대한화장품학회 2003 대한화장품학회지 Vol.29 No.1

Melanin biosynthesis is a human defense mechanism to protect skin from UV irradiation and also determines colors of hair and skin. However, as a interest on skin-whitening increases, researches to prevent pigmentation and hypersynthesis of melanin in skin are being actively in progress. Active components used as a whitening agent in cosmeceuticals are kojic acid, arbutin, vitamin C and hydroquinone. However, until now, because comparison researches among them in the aspect of both melanin formation and cellular toxicity have not been performed, we can't exactly estimate merits and defects of them as a whitening agent. To this end, we performed experiments to compare their effects on cell viability and melanin formation. As a first step, in vitro tyrosinase inhibition assay was done. While kojic acid and hydroquinone showed strong inhibition activities(their IC₅₀/s are all < 100uM), arbutin and vitamin C showed weak activities. IC₅₀/s of arbutin and vitamin C are 100uM and 400∼500uM, respectively. In B16BL6 melanoma cells, like in vitro tyrosinase inhibition assay, arbutin and kojic acid showed more strong inhibition effect on melanin synthesis than vitamin C. And unlike arbutin, vitamin C and kojic acid induced cell death at high concentration. Although arbutin showed no cytotoxicity, it has side effect to induce morphological change at high concentration.. In this paper, we suggest both kojic acid and arbutin have stronger ability to inhibit melanogenesis than vitamin C. And they also have side effect, that is, kojic acid induces cell death like vitamin C and arbutin changes cell morphology respectively.

Mitochondrial genome mutations in mesenchymal stem cells derived from human dental induced pluripotent stem cells

( Jumi Park ),( Yeonmi Lee ),( Joosung Shin ),( Hyeon-jeong Lee ),( Young-bum Son ),( Bong-wook Park ),( Deokhoon Kim ),( Gyu-jin Rho ),( Eunju Kang ) 생화학분자생물학회(구 한국생화학분자생물학회) 2019 BMB Reports Vol.52 No.12

Ethical and safety issues have rendered mesenchymal stem cells (MSCs) popular candidates in regenerative medicine, but their therapeutic capacity is lower than that of induced pluripotent stem cells (iPSCs). This study compared original, dental tissue-derived MSCs with re-differentiated MSCs from iPSCs (iPS-MSCs). CD marker expression in iPS-MSCs was similar to original MSCs. iPS-MSCs expressed higher in pluripotent genes, but lower levels in mesodermal genes than MSCs. In addition, iPS-MSCs did not form teratomas. All iPSCs carried mtDNA mutations; some shared with original MSCs and others not previously detected therein. Shared mutations were synonymous, while novel mutations were non-synonymous or located on RNA-encoding genes. iPS-MSCs also harbored mtDNA mutations transmitted from iPSCs. Selected iPS-MSCs displayed lower mitochondrial respiration than original MSCs. In conclusion, screening for mtDNA mutations in iPSC lines for iPS-MSCs can identify mutation-free cell lines for therapeutic applications. [BMB Reports 2019; 52(12): 689-694]

Asiaticoside induces Human Collagen I Synthesis through TGFβ receptor I kinase (TβRI kinase) -independent Smad signaling

Jongsung Lee,Eunsun Jung,Youngji Kim,Junho Park,Jinil Park,Sungtaek Hong,Jieun Kim,Changgu Hyun,Yeong Shik Kim,Deokhoon Park 한국생물공학회 2007 한국생물공학회 학술대회 Vol.2007 No.4

HSP90 inhibitor, AUY922, debilitates intrinsic and acquired lapatinib-resistant HER2-positive gastric cancer cells

( Kang-seo Park ),( Yong Sang Hong ),( Junyoung Choi ),( Shinkyo Yoon ),( Jihoon Kang ),( Deokhoon Kim ),( Kang-pa Lee ),( Hyeon-su Im ),( Chang Hoon Lee ),( Seyoung Seo ),( Sang-we Kim ),( Dae Ho Lee 생화학분자생물학회(구 한국생화학분자생물학회) 2018 BMB Reports Vol.51 No.12

Human epidermal growth factor receptor 2 (HER2) inhibitors, such as trastuzumab and lapatinib are used to treat HER2-positive breast and gastric cancers. However, as with other targeted therapies, intrinsic or acquired resistance to HER2 inhibitors presents unresolved therapeutic problems for HER2-positive gastric cancer. The present study describes investigations with AUY922, a heat shock protein 90 (HSP90) inhibitor, in primary lapatinib-resistant (ESO26 and OE33) and lapatinib-sensitive gastric cancer cells (OE19, N87, and SNU-216) harboring HER2 amplification/over-expression. In order to investigate whether AUY922 could overcome intrinsic and acquired resistance to HER2 inhibitors in HER2-positive gastric cancer, we generated lapatinib-resistant gastric cancer cell lines (OE19/LR and N87/LR) by continuous exposure to lapatinib in vitro. We found that activation of HER2 and protein kinase B (AKT) were key factors in inducing intrinsic and acquired lapatinib-resistant gastric cancer cell lines, and that AUY922 effectively suppressed activation of both HER2 and AKT in acquired lapatinib-resistant gastric cancer cell lines. In conclusion, AUY922 showed a synergistic anti-cancer effect with lapatinib and sensitized gastric cancer cells with intrinsic resistance to lapatinib. Dual inhibition of the HSP90 and HER2 signaling pathways could represent a potent therapeutic strategy to treat HER2-positive gastric cancer with intrinsic and acquired resistance to lapatinib. [BMB Reports 2018; 51(12): 660-665]

Air Pollution and Skin Health: Recent Studies

( Minkyung Kim ),( Hyunju Woo ),( Deokhoon Park ),정은선 ( Eunsun Jung ) 한국피부장벽학회 2018 한국피부장벽학회지 Vol.20 No.2

Air pollution is one of the biggest threat to human health in many industrializing countries. There are many kinds of substances that cause air pollution such as carbon dioxide, ozone, noxious fumes, fine dust, etc. Airborne particulate matters (PMs) are classified into coarse (2.5-10 μm), fine (< 2.5 μm), and ultrafine (< 0.1 μm), which are composed of ion components, hydrocarbons and metal compounds. Oxidative stress and aryl hydrocarbon receptor (AhR) activity is an important pathophysiological mechanism of pollutant-induced damage. The human skin, the outer layer of body is constantly exposed to the environmental pollutants. Exposure of skin to air pollutants is closely related to skin aging and inflammatory responses such as wrinkles formation, hyperpigmentation, atopic dermatitis, and acne. Thus, a great deal of interest has been focused on the development of material that can provide a protective effect to skin from pollutants. The purpose of this presentation is to review the current studies about the role of pollution on skin and development of protective material against pollutant induced skin damage.

Protective Effect of Mulberry (<i>Morus alba</i> L.) Extract against Benzo[a]pyrene Induced Skin Damage through Inhibition of Aryl Hydrocarbon Receptor Signaling

Woo, Hyunju,Lee, JungA,Park, Deokhoon,Jung, Eunsun American Chemical Society 2017 Journal of agricultural and food chemistry Vol.65 No.50

<P>Benzo[a]pyrene (B[a]P), a type of polycyclic aromatic hydrocarbon, is present in the atmosphere surrounding our environment. Although B[a]P is a procarcinogen, enzymatically metabolized benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE) could intercalate into DNA to form bulky BPDE-DNA adducts as an ultimate carcinogenic product in human keratinocytes. The aim of this study was to evaluate the protective effect of mulberry extract, purified from the fruit of <I>Morus Alba</I> L., on B[a]P-induced cytotoxicity in human keratinocytes and its mechanisms of action. In this study, we confirmed that B[a]P induced nuclear translocation and the activation of aryl hydrocarbon receptor (AhR) were decreased by pretreatment of mulberry extract. Mulberry extract could decrease DNA damage through the suppression of B[a]P derived DNA adduct formation and restoration of cell cycle retardation at S phase in a dose-dependent manner. Additionally, cyanidin-3-glucoside (C3G), a major active compound of mulberry extract, showed biological activities to protect the cells from B[a]P exposure, similar to the effectivity of the mulberry extract. These results indicated that the inhibitory effect of C3G against B[a]P inducing skin cancer is attributable to repress the AhR signaling pathway.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/jafcau/2017/jafcau.2017.65.issue-50/acs.jafc.7b04044/production/images/medium/jf-2017-040442_0007.gif'></P>

Development of anti wrinkle agents originated from some plants grow in Jeju island

Jongsung Lee,Eunsun Jung,Deokhoon Park 한국생물공학회 2008 한국생물공학회 학술대회 Vol.2008 No.10

Therapeutic relevance of targeted sequencing in management of patients with advanced biliary tract cancer: DNA damage repair gene mutations as a predictive biomarker

Chae, Heejung,Kim, Deokhoon,Yoo, Changhoon,Kim, Kyu-pyo,Jeong, Jae Ho,Chang, Heung-Moon,Lee, Sang Soo,Park, Do Hyun,Song, Tae Jun,Hwang, Shin,Kim, Ki-Hun,Song, Gi-Won,Ahn, Chul Soo,Lee, Jae Hoon,Hwang Elsevier 2019 European journal of cancer Vol.120 No.-

<P><B>Abstract</B></P> <P><B>Purpose</B></P> <P>In biliary tract cancer (BTC), standard chemotherapy has limited benefit and no molecular targeted agents have been approved. This study investigated the genetic profile of BTC to identify potential new therapeutic targets and predictive biomarkers.</P> <P><B>Methods</B></P> <P>Targeted exome sequencing was performed for 124 patients with BTC [gallbladder cancer (GBC), 25; intrahepatic cholangiocarcinoma (ICC), 55; extrahepatic cholangiocarcinoma (ECC), 44]. Survival analysis was performed in 112 patients who received palliative chemotherapy for locally unresectable or metastatic disease.</P> <P><B>Results</B></P> <P>Genetic alterations were observed in 104 patients (83.8%); the most commonly mutated genes were <I>TP53</I> (44.4%), <I>KRAS</I> (29.0%), <I>ARID1A</I> (12.1%) and <I>IDH1</I> (9.7%). <I>IDH1/2</I> mutations appeared more frequently in ICC (23.6%, P = 0.0002) than in GBC (4.0%) or ECC (2.3%), while <I>ERBB2</I>/<I>3</I> mutations were found only in GBC (20.0%) and ECC (11.4%). Patients harbouring <I>TP53</I> mutations had shorter overall survival (OS; median 15.2 vs. 37.8 months, <I>P</I> = 0.018), while <I>IDH1</I> mutations showed a tendency for longer progression-free survival (PFS; 10.6 vs. 6.1 months, <I>P</I> = 0.124). Potentially actionable genetic alterations were found in 54.8%, and 7.1% received appropriate molecular targeted therapy in the clinical trial setting. Germline or somatic mutations in DNA damage repair (DDR) genes were found in 63.5% of patients and were significantly associated with longer PFS (6.9 vs. 5.7 months, <I>P</I> = 0.013) and OS (21.0 vs. 13.3 months, <I>P</I> = 0.009) in patients who received first-line platinum-containing chemotherapies (n = 88).</P> <P><B>Conclusions</B></P> <P>A subgroup of patients with BTC may benefit from targeted therapy by the aid of genetic information. In particular, DDR alterations may be a predictive biomarker for response to platinum-containing chemotherapy in patients with BTC.</P> <P><B>Highlights</B></P> <P> <UL> <LI> We examined genetic landscape of biliary tract cancer with targeted sequencing. </LI> <LI> Certain genetic mutations were associated with clinical outcomes. </LI> <LI> More than half of patients harboured at least one potentially actionable alteration. </LI> <LI> DNA damage repair gene alterations were associated with a better response to platinum-based treatment. </LI> </UL> </P>

Effects of Ultraviolet A irradiation on adipogenic differentiation of human adipose tissue-derived mesenchymal stem cells

Jongsung Lee,Eunsun Jung,Jienny Lee,Deokhoon Park 한국생물공학회 2011 한국생물공학회 학술대회 Vol.2011 No.4

자외선 조사된 상피 줄기세포에 대한 붉나무 추출물의 보호 효과

우현주 ( Hyunjoo Woo ),유지영 ( Jiyoung You ),박덕훈 ( Deokhoon Park ),정은선 ( Eunsun Jung ) 대한화장품학회 2019 대한화장품학회지 Vol.45 No.4

피부 기저막에 위치하고 있는 인간 상피 줄기 세포는 피부상피층의 항상성 유지에 중요한 역할을 담당하고 있다. 비록 상피 줄기 세포가 조직손상에 대한 반응으로 상처 회복에 필요한 새로운 세포들을 공급하고 있지만 일부 세포는 정지 상태로 남아 생존을 위해 분화와 노화로부터 보호된다. 이러한 관점에서 적소세포와 외부세포기질 단백질로 구성된 특정 미세환경인 줄기세포 적소는 줄기세포를 보호하기 위해 적절한 자극을 제공해 준다. 줄기세포 마커는 상피 줄기세포의 표면에 발현되며, 기저막의 세포외기질과 부착하여 장기간의 성장 잠재력을 가지며 외부 자극에 대한 세포 사멸의 저항성을 가진다. 본 연구에서는 외부자극의 주요 인자로써 자외선 조사가 인테그린 α2, β1 와 α6 의 발현을 저하시킴을 확인하였으며 붉나무 추출물이 자외선에 의해 유도되어지는 인테그린 발현 저하를 억제하는 것을 확인 할 수 있었다. 또한 붉나무 추출물은 콜라겐IV와 라미닌과 같은 상피 줄기세포의 부착과 연관된 분자들의 발현을 상향조절 하였다. 이러한 결과는 붉나무 추출물이 줄기세포 표면의 인테그린의 발현을 증가시키고 적소에서의 세포외기질 성분의 발현을 증가시킴으로써 자외선 조사에 대한 보호효과가 있음을 확인하였다. Human epidermal stem cells(ESCs) residing in the basement membrane of the skin have an important role in maintenance of skin homeostasis of epidermal layer. Although, ESCs provide new cells to repair damaged tissue in response to tissue injury, subsets of stem cells remain in the quiescent state protected from differentiation and senescence for prolonged survivals. In this perspective, the stem cell niche, which is specific microenvironment composed of niche cells and an extracellular matrix(ECM), supplies the relevant signal to save stem cells from microenvironmental damages. The expression of stemness marker on the surface of ESCs contributes to the attachment on their ECM of the basement membrane, which lead to growth potential and apoptotic resistance against environmental stimuli. In this study, we observed that UV irradiation, a major factor of environmental stimuli, reduced the expression of α2, β1 and α6 integrin in ESCs. Rhus Semialata M extract(RSE) showed inhibitory effect on the UVB-induced reduction of integrin expression. Furthermore, RSE could upregulate the expression of Col-IV and Laminin, which contribute to the attachment of ESCs. These results indicated that RSE could be a potent ingredient for the protection of ESCs from UV irradiation by increasing the expression of integrin and substrate ECM components at their niche.