Comparison of Metabolic Profiles of Normal and Cancer Cells in Response to Cytotoxic Agents

이수진,강선미,박성혁 한국자기공명학회 2017 Journal of the Korean Magnetic Resonance Society Vol.21 No.1

Together with radiotherapy, chemotherapy using cytotoxic agents is one of the most common therapies in cancer. Metabolic changes in cancer cells are drawing much attention recently, but the metabolic alterations by anticancer agents have not been much studied. Here, we investigated the effects of commonly used cytotoxic agents on lung normal cell MRC5 and lung cancer cell A549. We employed cis-plastin, doxorubicin, and 5-Fluorouracil and compared their effects on the viability and metabolism of the normal and cancer cell lines. We first established the concentration of the cytotoxic reagents that give differences in the viabilities of normal and cancer cell lines. In those conditions, the viability of A549 decreased significantly, whereas that of MRC5 remained unchanged. To study the metabolic alterations implicated in the viability differences, we obtained the metabolic profiles using 1H-NMR spectrometry. The 1H-NMR data showed that the metabolic changes of A549 cells are more remarkable than that of MRC5 cells and the effect of 5-FU on the A549 cells is the most distinct compared to other treatments. Heat map analysis showed that metabolic alterations under treatment of cytotoxic agents are totally different between normal and cancer cells. Multivariate analysis and weighted correlation network analysis (WGCNA) revealed a distinctive metabolite signature and hub metabolites. Two different analysis tools revealed that the changes of cell metabolism in response to cytotoxic agents were highly correlated with the Warburg effect and Reductive lipogenesis, two pathways having important effects on the cell survival. Taken together, our study addressed the correlation between the viability and metabolic profiles of MRC5 and A549 cells upon the treatment of cytotoxic anticancer agents.

Comparison of Metabolic Profiles of Normal and Cancer Cells in Response to Cytotoxic Agents

Lee, Sujin,Kang, Sunmi,Park, Sunghyouk Korean Magnetic Resonance Society 2017 Journal of the Korean Magnetic Resonance Society Vol.21 No.1

Together with radiotherapy, chemotherapy using cytotoxic agents is one of the most common therapies in cancer. Metabolic changes in cancer cells are drawing much attention recently, but the metabolic alterations by anticancer agents have not been much studied. Here, we investigated the effects of commonly used cytotoxic agents on lung normal cell MRC5 and lung cancer cell A549. We employed cis-plastin, doxorubicin, and 5-Fluorouracil and compared their effects on the viability and metabolism of the normal and cancer cell lines. We first established the concentration of the cytotoxic reagents that give differences in the viabilities of normal and cancer cell lines. In those conditions, the viability of A549 decreased significantly, whereas that of MRC5 remained unchanged. To study the metabolic alterations implicated in the viability differences, we obtained the metabolic profiles using $^1H$-NMR spectrometry. The $^1H$-NMR data showed that the metabolic changes of A549 cells are more remarkable than that of MRC5 cells and the effect of 5-FU on the A549 cells is the most distinct compared to other treatments. Heat map analysis showed that metabolic alterations under treatment of cytotoxic agents are totally different between normal and cancer cells. Multivariate analysis and weighted correlation network analysis (WGCNA) revealed a distinctive metabolite signature and hub metabolites. Two different analysis tools revealed that the changes of cell metabolism in response to cytotoxic agents were highly correlated with the Warburg effect and Reductive lipogenesis, two pathways having important effects on the cell survival. Taken together, our study addressed the correlation between the viability and metabolic profiles of MRC5 and A549 cells upon the treatment of cytotoxic anticancer agents.

악성 종양세포주에서 세포독성 물질에 의한 apoptosis의 유발에 관한 연구

김병주,이상목,고석환,윤충,박재훈,장린 경희대학교 1997 慶熙醫學 Vol.13 No.4

화장품 원료의 피부자극성과 세포독성의 관련성

이은희(Eun Hee Lee),이종권(Jong Kwon Lee),김용규(Yong Kyu Kim),박기숙(Ki Sook Park),안광수(Kwang Soo Ahn),정경미(Kyoung Mi Jung),정해관(Jung Hai Kwan),이선희(Sun Hee Lee),정수연(Soo Youn Chung),홍진태(Jin Tae Hong) 대한약학회 2001 약학회지 Vol.45 No.3

To compare skin irritation and cytotoxicity of anti-wrinkle agents, we examined skin irritation of six anti-wrinkle agents (ascorbic acid, glycolic acid, all trans-retinoic acid, ginseng extract, retinol, EB) in New Zeland white rabbit. Cytotoxicity of these agents was determined by MTT [tetrasolium salt 3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyl tetrazolium bromide] at multi-time points in cultured HaCaT cell, a human immortalized keratinocyte cell. We then analyzed correlation between skin irritation and cytotoxicity by spearman's rank correlation analysis. All trans- retinoic acid shewed the highest primary irritation index (0.92) in skin irritation test. Being all the six agents not irritant, retinol showed the most cytotoxic agents. The correlation between skin irritation and cytotoxicity IC50 at different time point was 0.814,0.757,0.814 and 0.7 at 3,24, 48 and 72h, respectively. We also found that IC20 and IC80 of these agents showed similar correlation with skin irritation. These results therefore demonstrated that there is close correlation between skin irritation and cytotoxicity IC50 value by MTT in HaCaT cell at early time points by anti-wrinkle agents or IC20value. IC50 at earily time point or IC20 values may be reliable alter- native determinant of skin irritation.

Non-cytotoxic Antifungal Agents: Isolation and Structures of Gageopeptides A–D from a <i>Bacillus</i> Strain 109GGC020

Tareq, Fakir Shahidullah,Lee, Min Ah,Lee, Hyi-Seung,Lee, Yeon-Ju,Lee, Jong Seok,Hasan, Choudhury M.,Islam, Md. Tofazzal,Shin, Hee Jae American Chemical Society 2014 Journal of agricultural and food chemistry Vol.62 No.24

<P>Antifungal resistance and toxicity problems of conventional fungicides highlighted the requirement of search for new safe antifungal agents. To comply with the requirement, we discovered four new non-cytotoxic lipopeptides, gageopeptides A–D, <B>1–4,</B> from a marine-derived bacterium <I>Bacillus subtilis</I>. The structures and stereochemistry of gageopeptides were determined by NMR data analysis and chemical means. Gageopeptides exhibited significant antifungal activities against pathogenic fungi <I>Rhizoctonia solani</I>, <I>Botrytis cinerea</I>, and <I>Colletotrichum acutatum</I> with minimum inhibitory concentration (MIC) values of 0.02–0.06 μM. In addition, these lipopeptides showed significant motility inhibition and lytic activities against zoospores of the late blight pathogen <I>Phytophthora capsici</I>. These compounds also showed potent antimicrobial activity against Gram positive and Gram negative bacteria with MIC values of 0.04–0.08 μM. However, gageopeptides A–D did not exhibit any cytotoxicity (GI<SUB>50</SUB> > 25 μM) against cancer cell lines in sulforhodamine B (SRB), 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT), and WST-1 ((4-[3–4-iodophenyl]-2-(4-nitrophenyl)-2<I>H</I>-5-tetrazolio)-1,3-benzene disulfonate)) assays, demonstrating that these compounds could be promising candidates for the development of non-cytotoxic antifungal agents.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/jafcau/2014/jafcau.2014.62.issue-24/jf502436r/production/images/medium/jf-2014-02436r_0005.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/jf502436r'>ACS Electronic Supporting Info</A></P>

Cytotoxicity and antimicrobial effects of the methanolic extract of Sophora flavescens Ait. (IV)

Baek, Seung-Hwa,Kang, Kil-Ung,Lee, Jeong-Ho,Park, Nang-Kyu,Chai, Kyu-Yun,You, Il-Soo,Kim, Jong-Soo,Ryu, Do-Gon,Lee, Kang-Min,Yang, Eun-Yeong,Lee, Hyun-Ok Kyung Hee Oriental Medicine Research Center 2000 International journal of oriental medicine Vol.1 No.2

This study was carried out to evaluate cytotoxicity of the methanol extract from Sophora flavescens Ait. against L1210 (lymphocytic leukemia) and $P388D_1$ (lymphoid neoplasma) Cells in vitro. We have determined cytotoxicity by the MTT (3- (4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H- tetrazolium bromide) assay. The order of cytotoxicity of Sophora flavescens Ait. extracts against L1210 and $P388D_1$ cells in vitro is as follows: Fr. 4 > Fr. 3 > Fr. 5 > Fr. 2 > Fr. 1. These results suggest that the fraction 4 of the methanol extracts from Sophora flavescens Ait. may be a valuable choice for the development of antitumor agents. In order to develop an antimicrobial agent, dried Sophora flavescens Ait. was extracted with hot methanol, and then antimicrobial activity (MIC test) was investigated. In this study, the fraction 3 of the methanol extracts from the roots of S. flavescens showed strong growth inhibition activity against gram-positive and gram-negative bacteria (MIC, $3.125\;{\mu}g/ml$) such as S. mutans, S. epidermidis and P. putida. These results indicate that fractions 3 and 4 inhibit tumor cells and bacteria.

Synthesis and in vitro Antitumor Activity of lsoazamitosene and lsoiminoazamitosene Derivatives

Ahn, Chan-Mug,Kim, Soo-Kie The Pharmaceutical Society of Korea 1996 Archives of Pharmacal Research Vol.19 No.6

Seven isoazamitosene derivatives, mitomycin analogues, were synthesized and tested for cytotoxicities against leukemia and gastric cancer cell lines. Preparation of a pyrrolo[1, 2-a]benzimidazole (3) (azamitosene ring system) was completed by utilizing the Lewis acid-catalized cyclization, with .omicron.-chloronitrotoluene as the starting material. Nitration of 3 produced a mixtue of two isomers (5-nitro isomer (4) and 7-nitro isomer (5)) in product ratio of 36 : 52. 4 was directly converted into quinone (7) by reduction and Fremy oxidaton. Finally, quinone derivatives (8, 9, 10, and 11) were synthesized by 1, 4-addition of 7 with cyclic secondary amines. From above-mentioned 5, 8-nitro compound (15) was prepared in 4 steps. At pH 3, Fremy oxidation of 15 produced quinone (16), whereas iminoquinone derivatives (17a and 17b) at pH 7. Isoazamitosene derivatives (8, 9, 10, and 11), containing cyclic amino groups at the 7-position, showed potent cytotoxicity on P388, SNU-1, and KHH tumor cell lines. Among them, 8 had stronger cytotoxicity against SNU-1 cell line than mitomycin and adriamycin. Considering these results, isoazamitosene derivatives may had unique cytotoxicity profiles. However, isoiminoazamitosene derivatives (17a and 17b) revealed very weak cytotoxicity.

Physicochemical Characterization and Cytotoxic Screening of Diterpene acid

Choi Eun Young,Lim Jin A,Lee Jae Sug,Yu Byung Soo,Baek Seung Hwa The Physiological Society of Korean Medicine and T 2004 동의생리병리학회지 Vol.18 No.6

The diterpene acid (1) was tested for its growth inhibitory effects against tumor cell lines using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Full assignments of the 1D/2D-NMR data of the compound (1) are reported. These results suggest that the diterpene acid (1) possessed a cytotoxic agent.

항종양활성천연약물연구의 전망

히데치 한국자원식물학회 1992 한국자원식물학회지 Vol.5 No.2

Many types of compounds have been isolated from higher plants till now, that is, alkaloids, terpenes, lignans, steroids and so on. One of them, named as RA series Cyclic hexapeptides isolated from Rubia akane and R. cordijofia also have strong antineoplastic activity against various types of tumors. Till now 10 kinds ofRA series compounds were isolated and named as RA - I, II, III, IV, V, VI, VII, VIII, IX and X. Moreover,monogl-ucoside of RA - V newly Isolated from same plant. Many kinds of derivatives including natural RAcompounds were tested for QSAR, and one of them, RA - VII was screened up as a most suitable substance asan antitumor agent. RA - VII(=RA-700) has strong cytotoxic activity against KB cells, P388 Iymphocyticleukemia and MM2 mammary carcinoma cells. RA - VII has been under investigation for Phase I clinical trials.

Bimodal Approach for the Use of Co Doped Magnetite as MRI Contrast Agent and Potential Antitumor

Ahmed. A. G. El-Shahawy,Yasser GadelHak,H. Y. Zahran,I. S. Yahia,S. I. El-Dek 한국자기학회 2020 Journal of Magnetics Vol.25 No.4

Cobalt doped magnetite Co<SUP>2+</SUP> 0.1Fe<SUP>2+</SUP> 0.9Fe<SUP>3+</SUP> ₂O₄ nanocrystals were synthesized chemically using simple one step coprecipitation in the absence and presence of the magnetic field. The nanocrystals were characterized by transmission electron microscopy (TEM), X-ray diffraction (XRD), magnetization studies by vibrational spectroscopy magnetometer (VSM). The signal intensity of the prepared nanoparticles was measured by magnetic resonance imaging (MRI). The cytotoxicity of the two samples versus W138 normal lung cells and AS49 lung cancer cells was investigated by MTT assay, in vitro. The TEM images showed non-spherical and aggregated nanoparticles, heterogeneously dispersed with 100 nm average size. The XRD and selected area electron diffraction of the two samples revealed good crystallinity for both samples. The room temperature magnetization curves demonstrate the general ferrimagnetic trend with a clear difference in the coercivity and the remanence keeping the saturation magnetization nearly stable. The measured MR signal intensity was well-matched with the result of the M-H loops where the sample prepared in the absence of the field was a promising T2 contrast agent. Both samples have low cytotoxicity compared to Doxorubicin.