• Title/Summary/Keyword: curcumin

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Selective Effects of Curcumin on CdSe/ZnS Quantum-dot-induced Phototoxicity Using UVA Irradiation in Normal Human Lymphocytes and Leukemia Cells

  • Goo, Soomin;Choi, Young Joo;Lee, Younghyun;Lee, Sunyeong;Chung, Hai Won
    • Toxicological Research
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    • v.29 no.1
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    • pp.35-42
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    • 2013
  • Quantum dots (QDs) have received considerable attention due to their potential role in photosensitization during photodynamic therapy. Although QDS are attractive nanomaterials due to their novel and unique physicochemical properties, concerns about their toxicity remain. We suggest a combination strategy, CdSe/ZnS QDs together with curcumin, a natural yellow pigment from turmeric, to reduce QD-induced cytotoxicity. The aim of this study was to explore a potentially effective cancer treatment: co-exposure of HL-60 cells and human normal lymphocytes to CdSe/ZnS QDs and curcumin. Cell viability, apoptosis, reactive oxygen species (ROS) generation, and DNA damage induced by QDs and/or curcumin with or without ultraviolet A (UVA) irradiation were evaluated in both HL-60 cells and normal lymphocytes. In HL-60 cells, cell death, apoptosis, ROS generation, and single/double DNA strand breaks induced by QDs were enhanced by treatment with curcumin and UVA irradiation. The protective effects of curcumin on cell viability, apoptosis, and ROS generation were observed in normal lymphocytes, but not leukemia cells. These results demonstrated that treatment with QD combined with curcumin increased cell death in HL-60 cells, which was mediated by ROS generation. However, curcumin acted as an antioxidant in cultured human normal lymphocytes.

PRP4 Kinase Domain Loss Nullifies Drug Resistance and Epithelial-Mesenchymal Transition in Human Colorectal Carcinoma Cells

  • Ahmed, Muhammad Bilal;Islam, Salman Ul;Sonn, Jong Kyung;Lee, Young Sup
    • Molecules and Cells
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    • v.43 no.7
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    • pp.662-670
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    • 2020
  • We have investigated the involvement of the pre-mRNA processing factor 4B (PRP4) kinase domain in mediating drug resistance. HCT116 cells were treated with curcumin, and apoptosis was assessed based on flow cytometry and the generation of reactive oxygen species (ROS). Cells were then transfected with PRP4 or pre-mRNA-processing-splicing factor 8 (PRP8), and drug resistance was analyzed both in vitro and in vivo. Furthermore, we deleted the kinase domain in PRP4 using Gateway™ technology. Curcumin induced cell death through the production of ROS and decreased the activation of survival signals, but PRP4 overexpression reversed the curcumin-induced oxidative stress and apoptosis. PRP8 failed to reverse the curcumin-induced apoptosis in the HCT116 colon cancer cell line. In xenograft mouse model experiments, curcumin effectively reduced tumour size whereas PRP4 conferred resistance to curcumin, which was evident from increasing tumour size, while PRP8 failed to regulate the curcumin action. PRP4 overexpression altered the morphology, rearranged the actin cytoskeleton, triggered epithelial-mesenchymal transition (EMT), and decreased the invasiveness of HCT116 cells. The loss of E-cadherin, a hallmark of EMT, was observed in HCT116 cells overexpressing PRP4. Moreover, we observed that the EMT-inducing potential of PRP4 was aborted after the deletion of its kinase domain. Collectively, our investigations suggest that the PRP4 kinase domain is responsible for promoting drug resistance to curcumin by inducing EMT. Further evaluation of PRP4-induced inhibition of cell death and PRP4 kinase domain interactions with various other proteins might lead to the development of novel approaches for overcoming drug resistance in patients with colon cancer.

Effects of Curcumin from Turmeric Supplementation in Freezing Buffer on Sperm Motilities and Reactive Oxygen Species Generation (동결보존액에 울금에서 추출한 Curcumin의 첨가가 정자의 운동성과 활성산소 생성에 미치는 영향)

  • Lee, Eun-Joo;Kim, Dae-Young
    • Journal of Embryo Transfer
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    • v.32 no.3
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    • pp.249-255
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    • 2017
  • In this experiment, we determined the effect of curcumin supplementation in freezing buffer for miniature pig sperm cryopreservation. Each ejaculate was diluted with modified Modena B extender and mixed with lactose-egg yolk (LEY extender, 80% v/v lactose solution [310 mM], 20% v/v egg yolk, and $100{\mu}g/mL$ kanamycin sulfate) and LEY-glycerol Orvus ES Paste (LEYGO, 89.5% v/v LEY, 5% v/v glycerol, 1.5% v/v Orvus ES Paste), 100 mM trehalose supplemented with 0, 10, 50, 100, and $500{\mu}M$ of curcumin from turmeric, respectively. Following equilibration, the 0.5 mL French straws were frozen and plunged into $LN_2$ tank for 7 days at least. Sperm parameter and oxidative byproducts were determined by the computer assisted sperm motility analysis (CASA) and fluorescence-activated cell sorting (FACS) as compared with each groups. Supplementation of curcumin had no effect on sperm motility, progressive motility and curvilinear velocity. However, average-path velocity and straight-line velocity were significantly higher in $10{\mu}M$ curcumin group ($100.9{\pm}8.8{\mu}m/s$, $61.7{\pm}2.9{\mu}m/s$, respectively) than control group ($77.8{\pm}3.9{\mu}m/s$, $46.4{\pm}3.0{\mu}m/s$, respectively) (p < 0.05). In addition, the level of the O2 radical and H2O2 were comparatively decreased in curcumin groups by evaluation of ethidium and DCF fluorescence. According to the results, curcumin can improve sperm kinetic variables and alleviate ROS induced cryoinjury to pig sperm.

Curcumin targets vascular endothelial growth factor via activating the PI3K/Akt signaling pathway and improves brain hypoxic-ischemic injury in neonatal rats

  • Li, Jia;An, Yan;Wang, Jia-Ning;Yin, Xiao-Ping;Zhou, Huan;Wang, Yong-Sheng
    • The Korean Journal of Physiology and Pharmacology
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    • v.24 no.5
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    • pp.423-431
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    • 2020
  • This study aimed to evaluate the effect of curcumin on brain hypoxic-ischemic (HI) damage in neonatal rats and whether the phosphoinositide 3-kinase (PI3K)/Akt/vascular endothelial growth factor (VEGF) signaling pathway is involved. Brain HI damage models were established in neonatal rats, which received the following treatments: curcumin by intraperitoneal injection before injury, insulin-like growth factor 1 (IGF-1) by subcutaneous injection after injury, and VEGF by intracerebroventricular injection after injury. This was followed by neurological evaluation, hemodynamic measurements, histopathological assessment, TUNEL assay, flow cytometry, and western blotting to assess the expression of p-PI3K, PI3K, p-Akt, Akt, and VEGF. Compared with rats that underwent sham operation, rats with brain HI damage showed remarkably increased neurological deficits, reduced right blood flow volume, elevated blood viscosity and haematocrit, and aggravated cell damage and apoptosis; these injuries were significantly improved by curcumin pretreatment. Meanwhile, brain HI damage induced the overexpression of p-PI3K, p-Akt, and VEGF, while curcumin pretreatment inhibited the expression of these proteins. In addition, IGF-1 treatment rescued the curcumin-induced down-regulated expression of p-PI3K, p-Akt, and VEGF, and VEGF overexpression counteracted the inhibitory effect of curcumin on brain HI damage. Overall, pretreatment with curcumin protected against brain HI damage by targeting VEGF via the PI3K/Akt signaling pathway in neonatal rats.

Curcumin attenuates renal ischemia reperfusion injury via JNK pathway with the involvement of p300/CBP-mediated histone acetylation

  • Yang, Lu;Chen, Xiaoxiang;Bi, Zirong;Liao, Jun;Zhao, Weian;Huang, Wenqi
    • The Korean Journal of Physiology and Pharmacology
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    • v.25 no.5
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    • pp.413-423
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    • 2021
  • Apoptosis is proved responsible for renal damage during ischemia/reperfusion. The regulation for renal apoptosis induced by ischemia/reperfusion injury (IRI) has still been unclearly characterized to date. In the present study, we investigated the regulation of histone acetylation on IRI-induced renal apoptosis and the molecular mechanisms in rats with the application of curcumin possessing a variety of biological activities involving inhibition of apoptosis. Sprague-Dawley rats were randomized into four experimental groups (SHAM, IRI, curcumin, SP600125). Results showed that curcumin significantly decreased renal apoptosis and caspase-3/-9 expression and enhanced renal function in IRI rats. Treatment with curcumin in IRI rats also led to the decrease in expression of p300/cyclic AMP response element-binding protein (CBP) and activity of histone acetyltransferases (HATs). Reduced histone H3 lysine 9 (H3K9) acetylation was found near the promoter region of caspase-3/-9 after curcumin treatment. In a similar way, SP600125, an inhibitor of c-Jun N-terminal kinase (JNK), also attenuated renal apoptosis and enhanced renal function in IRI rats. In addition, SP600125 suppressed the binding level of p300/CBP and H3K9 acetylation near the promoter region of caspase-3/-9, and curcumin could inhibit JNK phosphorylation like SP600125. These results indicate that curcumin could attenuate renal IRI via JNK/p300/CBP-mediated anti-apoptosis signaling.

6-Shogaol and 10-Shogaol Synergize Curcumin in Ameliorating Proinflammatory Mediators via the Modulation of TLR4/TRAF6/MAPK and NFκB Translocation

  • Xian Zhou;Ahmad Al-Khazaleh;Sualiha Afzal;Ming-Hui (Tim) Kao;Gerald Munch;Hans Wohlmuth;David Leach;Mitchell Low;Chun Guang Li
    • Biomolecules & Therapeutics
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    • v.31 no.1
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    • pp.27-39
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    • 2023
  • Extensive research supported the therapeutic potential of curcumin, a naturally occurring compound, as a promising cytokine-suppressive anti-inflammatory drug. This study aimed to investigate the synergistic anti-inflammatory and anti-cytokine activities by combining 6-shogaol and 10-shogaol to curcumin, and associated mechanisms in modulating lipopolysaccharides and interferon-γ-induced proinflammatory signaling pathways. Our results showed that the combination of 6-shogaol-10-shogaolcurcumin synergistically reduced the production of nitric oxide, inducible nitric oxide synthase, tumor necrosis factor and interlukin-6 in lipopolysaccharides and interferon-γ-induced RAW 264.7 and THP-1 cells assessed by the combination index model. 6-shogaol-10-shogaol-curcumin also showed greater inhibition of cytokine profiling compared to that of 6-shogaol-10-shogaol or curcumin alone. The synergistic anti-inflammatory activity was associated with supressed NFκB translocation and downregulated TLR4-TRAF6-MAPK signaling pathway. In addition, SC also inhibited microRNA-155 expression which may be relevant to the inhibited NFκB translocation. Although 6-shogaol-10-shogaol-curcumin synergistically increased Nrf2 activity, the anti-inflammatory mechanism appeared to be independent from the induction of Nrf2. 6-shogaol-10-shogaol-curcumin provides a more potent therapeutic agent than curcumin alone in synergistically inhibiting lipopolysaccharides and interferon-γ induced proinflammatory mediators and cytokine array in macrophages. The action was mediated by the downregulation of TLR4/TRAF6/MAPK pathway and NFκB translocation.

Study on the Attributive Channel Theory by the Pharmacodynamic Research of I-131 labelled Curcumin (I-131 표지 Curcumin의 약동력학적 분석을 통한 귀경(歸經)연구)

  • Yun, Hong-Il;Ham, In-Hye;Cho, Jung-Hyuck;Yu, Kook-Hyun;Park, Jung-Hoon;Choi, Ho-Young
    • The Korea Journal of Herbology
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    • v.22 no.2
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    • pp.181-188
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    • 2007
  • Objectives : This study was to verify the Attributive Channel theory of herbal medicine. Methods : [13lI]iodocurcumin was synthesized, separated, and refined from curcumin, the major component of Curcuma species, followed by observing the biodistribution in an organism. Especially, from the fact that curcumin has shown to possess potent anti-carcinogenic properties, the biodistribution in the carcinogenesis organism was analyzed. Result : Iodocurcumin 23mg was obtained through column chromatography after a reaction with 50mg of Curcumin and ICl. The nominal yield of [13lI]iodocurcumin synthesis was 35% when checked with radioactive layer of chromatography. [13lI]iodocurcumin was most largely distributed in the stomach of a BALB/c mouse and a C57BL/6 mouse transplanted with Lewis lung carcinoma cell. Conclusion : The fact that [13lI]iodocurcumin was most largely distributed in the stomach was related with the Attributive Channel theory. And there was no significant finding related to tumor cells.

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Reversal of Resistance towards Cisplatin by Curcumin in Cervical Cancer Cells

  • Roy, Madhumita;Mukherjee, Sutapa
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.3
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    • pp.1403-1410
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    • 2014
  • Epigenetic regulators like histone deacetylases (1 and 2), and viral onco-proteins (E6/E7) are known to be overexpressed in cervical cancer cells. The present study was designed to investigate the effect of curcumin on HDACs (1 and 2) and HPV E6/E7 in the cervical cancer cell line SiHa and a drug resistant clone $SiHa^R$ (derived from SiHa). It was further intended to investigate whether curcumin could sensitize the cells towards cisplatin induced cell killing by modulation of multi drug resistant proteins like MRP1 and Pgp1. Curcumin inhibited HDACs, HPV expression and differentially increased acetylation and up-regulation of p53 in SiHa and $SiHa^R$, leading to cell cycle arrest at G1-S phase. Up-regulation of pRb, p21, p27 and corresponding inhibition of cyclin D1 and CDK4 were observed. Cisplatin resistance in $SiHa^R$ due to over-expression of MRP1 and Pgp1 was overcome by curcumin. Curcumin also sensitized both the cervical cancer cells towards cisplatin induced cell killing. Inhibition of HDACs and HPVs led to cell cycle arrest at G1/S phase by alteration of cell cycle regulatory proteins. Suppression of MRP1 and Pgp1 by curcumin resulted in sensitization of cervical cancer cells, lowering the chemotherapeutic dose of the drug cisplatin.

Apoptotic Effects of Curcumin on the Epstein-Barr Virus-Transformed Human B Lymphoma Cells Activated by PWM (Curcumin이 PWM에 의해 활성화된 Epstein-Barr 바이러스 변형 사람 B 림프종 세포의 사멸에 미치는 효과)

  • Ryu, Sang-Chae;Lee, Jang-Suk;Chong, Myong-Soo;Lee, Ki-Nam
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.26 no.3
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    • pp.287-292
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    • 2012
  • The results of this study intended to clarify the apoptotic effects of curcumin on Epstein-Barr virus transformed human B lymphoma (EBV-B) cells are summarized as follows: It was found that curcumin induced endoplasmic reticulum(ER) stress as well as apoptotic cell death in EBV-B cells, although the magnitude of action was insignificant. When EBV-B cells activated by pokeweed mitogen (PWM) were treated with the same concentrations of curcumin, it was found that higher ER stress (GRP78, P-PERK, XBP-1, ATF6, and CHOP expressed) increased unfold protein response (UPR) and thus, apoptosis attributed to ER stress, compared to non-activated EBV-B cells In conclusion, it is expected that curcumin will play an important role for leukemia treatment.

Synergistic Anti-tumor Effect of KLF4 and Curcumin in Human Gastric Carcinoma Cell Line

  • Ji, Jun;Wang, He-Shuang;Gao, Yan-Yan;Sang, Li-Min;Zhang, Li
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.18
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    • pp.7747-7752
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    • 2014
  • Kr$\ddot{u}$ppel-like factor 4 is a transcription factor which plays an important role in development and progression of various carcinomas. Curcumin characterized by excellent anti-cancer properties is regarded as a serviceable natural compound used in carcinoma therapy. This study aimed at exploring the impact of KLF4 overexpression in cooperation with curcumin on the proliferation, apoptosis and invasion of human gastric carcinoma BGC-823 cells. Flow cytometry analysis, CCK-8 assays, transwell assays and Western blot results showed that KLF4 overexpression combined with curcumin had significant anti-proliferation, pro-apoptosis and anti-invasion effects on BGC-823 cells. We also found that KLF4 had synergistic effects with curcumin, better promoting apoptosis and inhibiting proliferation and invasion of gastric carcinona cells. These results indicate that KLF4 could be used as a potential therapeutic target; curcumin could act as an auxiliary and provide a promising therapeutic strategy in stomach cancer.