BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH
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2018
·
IF 1.492
Liu Zi-Jun,Wang Ya-Lan,Li Qi-Ling,Yang Liu
Cuscuta chinensis polysaccharide (CPS) was extracted using hot water and enzymatically hydrolyzed C. chinensis polysaccharide (ECPS) was produced by the mannase enzymatic hydrolysis process. The purpose of this research was to investigate the antimelanogenic activity of ECPS and CPS in B16F10 melanoma cells. The in vitro antioxidant activity was assessed by their ferric iron reducing power and DPPH free radical scavenging activities. The molecular mass distribution of polysaccharides was determined using SEC-MALLS-RI. CPS was successfully enzymatically degraded using mannase and the weighted average molecular weights of CPS and ECPS were 434.6 kDa and 211.7 kDa. The results of biological activity assays suggested that the enzymatically hydrolyzed polysaccharide had superior antimelanogenic activity and antioxidant effect than the original polysaccharide. ECPS exhibited antimelanogenic activity by down-regulating the expression of tyrosinase, MITF, and TRP-1 without cytotoxic effects in B16F10 melanoma cells. In conclusion, ECPS have the potential to become a skin whitening product.
研究领域:
生物化学
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药理学
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化妆品科学
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DOI
PubMed
高影响因子
Chemistry-An Asian Journal
·
2021
·Vol. 16
·期 19
·2993-3000
·
IF 4.568
Pan Wang,Jian-Wei Wang,Wen-Hua Zhang,Hongzhen Bai,Guping Tang,David J. Young
Graphical Nanoformulations of a class of mononuclear and dinuclear Pt-based complexes bearing Pt−P bonds have been developed as efficient chemotherapeutic reagents against murine melanoma cell line B16F10. Nanoformulations of mononuclear Pt complexes cis -PtCl 2 (PPh 3 ) 2 ( 1 ), [Pt(PPh 3 ) 2 (L−Cys)] ⋅ H 2 O ( 3 , L−Cys=L-cysteinate), trans -PtCl 2 (PPh 2 PhNMe 2 ) 2 ( 4 ; PPh 2 PhNMe 2 =4-(dimethylamine)triphenylphosphine), trans -PtI 2 (PPh 2 PhNMe 2 ) 2 ( 5 ) and dinuclear Pt cluster Pt 2 ( μ -S) 2 (PPh 3 ) 4 ( 2 ) have comparable cytotoxicity to cisplatin against murine melanoma cell line B16F10. Masking of these discrete molecular entities within the hydrophobic core of Pluronic® F-127 significantly boosted their solubility and stability, ensuring efficient cellular uptake, giving in vitro IC 50 values in the range of 0.87–11.23 μM. These results highlight the potential therapeutic value of Pt complexes featuring stable Pt−P bonds in nanocomposite formulations with biocompatible amphiphilic polymers.
研究领域:
药理学
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肿瘤学
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纳米医学
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DOI
高影响因子
Chinese Journal of Natural Medicines
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2018
·
IF 1.991
Rakotomalala Manda Heriniaina,Jing DONG,Praveen Kumar Kalavagunta,Hua-Li WU,Dong-Sheng YAN,Jing SHANG
Several chemical compounds can restore pigmentation in vitiligo through mechanisms that vary according to disease etiology. In the present study, we investigated the melanogenic activity of six structurally distinct compounds, namely, scopoletin, kaempferol, chrysin, vitamin D 3 , piperine, and 6-benzylaminopurine. We determined their effectiveness, toxicity, and mechanism of action for stimulating pigmentation in B16F10 melanoma cells and in a zebrafish model. The melanogenic activity of 6-benzylaminopurine, the compound identified as the most potent, was further verified by measuring green fluorescent protein concentration in tyrp1 a: eGFP (tyrosinase-related protein 1) zebrafish and mitfa: eGFP (microphthalmia associated transcription factor) zebrafish and antioxidative activity. All the tested compounds were found to enhance melanogenesis responses both in vivo and in vitro at their respective optimal concentration by increasing melanin content and expression of TYR and MITF. 6-Benzyamino-purine showed the strongest re-pigmentation action at a concentration of 20 μmol·L −1 in vivo and 100 μmol·L −1 in vitro , and up-regulated the strong fluorescence expression of green fluorescent protein in tyrp1a: eGFP and mitfa: eGFP zebrafish in vitro . However, its relative anti-oxidative activity was found to be very low. Overall, our results indicated that 6-benzylaminopurine stimulated pigmentation through a direct mechanism, by increasing melanin content via positive regulation of tyrosinase activity in vitro , as well as up-regulating the expression of the green fluorescent protein in transgenic zebrafish in vivo .
研究领域:
药理学
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皮肤病学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Medicinal Chemistry
·
2017
·Vol. 13
·期 8
·753-760
·
IF 2.331
Guo Ping,Xie Zixin,Zhang Huan,Zhang Zaikui,Han Chao,Cheng Donghua,Lin Dan,Zhang Yuan,Wang Xuebao,Guo Xin,Ye Faqing
Background: Thienopyrimidinone is a newly designed, selective fibroblast growth factor receptor 1 (FGFR1) inhibitor with an excellent anticancer effect. Objective: The goal of the present study was to design and synthesize better FGFR1 inhibitors through modifications of the lead
compound thienopyrimidinone. Methods: In the present study, a series of C-2 substituted derivatives of thienopyrimidinone, namely L1-L16, were synthesized, and their inhibitory effects on FGFR1 were evaluated. The anti-proliferative activities of these compounds were assessed by MTT assay.
Results: Among the novel derivatives, L11 was found to exert remarkable FGFR1 inhibitory activity (79.93% at 10 μM) and anti-proliferative activity, with IC50 values of 2.1, 2.5, and 3.5 µM in the FGFR1-overexpressing cell lines, H460, HT-1197, and B16F10, respectively.
Conclusion: Our newly synthesized thienopyrimidinone derivatives may be candidate FGFR1 inhibitors for future development as novel anticancer agents.
研究领域:
药理学
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肿瘤学
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药物化学
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DOI
PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2022
·
IF 6.064
Jiang Mingyue,Chen Le,Chen Bo,Yu Qinghua,Zhang Xianming,Jing Weihong,Ma Limei,Deng Tao,Yang Zhangyou,Yu Chao
Curcumin (CUR) is a natural bioactive compound that has attracted attention as a “golden molecule” due to its therapeutic properties against several types of tumors. Nonetheless, the antitumor application of CUR is hampered due to its extremely low aqueous solubility and chemical instability. Herein, a novel type of CUR-loaded polymeric micelles with intracellular K+-responsive controlled-release properties is designed and developed. The polymeric micelles are self-assembled by poly (N-isopropylacrylamide-co-acryloylamidobenzo-15-crown-5-co-N, N-dimethylacrylamide)-b-DSPE (PNDB-b-DSPE) block copolymers, and CUR. CUR is successfully loaded into the micelles with a CUR loading content of 6.26 wt%. The proposed CUR-PNDB-DSPE polymeric micelles exhibit a significant CUR release in simulated intracellular fluid due to the formation of 2 : 1 ‘‘sandwich’’ host–guest complexes of 15-crown-5 and K+, which lead to the hydrophilic outer shell of micelles to collapse and the drug to rapidly migrate out of the micelles. In vitro, the B16F10 cell experiment indicates that CUR-PNDB-DSPE micelles exhibit a high cellular uptake and excellent intracellular drug release in response to the intracellular K+ concentration. Moreover, CUR-PNDB-DSPE micelles show high cytotoxicity to B16F10 cells compared to free CUR and CUR-PEG-DSPE micelles. The polymeric micelles with intracellular K+-responsive controlled release properties proposed in this study provide a new strategy for designing novel targeted drug delivery systems for CUR delivery for cancer treatment.
研究领域:
药学
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纳米技术
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癌症研究
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材料科学
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产品关联
DOI
PubMed
高影响因子
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY
·
2025
·
IF 4.3
Chanlin Fang,Shanshan Di,Yuekai Zhang,Xinquan Wang,Yuanxiang Jin
N-(1,3-Dimethylbutyl)- N ′-phenyl- p -phenylenediamine (6PPD), a critical antioxidant in rubber manufacturing, has raised global concerns due to its environmental persistence and toxic transformation products. While its developmental toxicity is increasingly recognized, the mechanisms underlying melanogenesis disruption in fish remain poorly understood. In this study, we systematically investigated 6PPD's effects on melanin synthesis in zebrafish embryos and murine melanoma cells (B16F10). Larval zebrafish were exposed to 10 and 100 μg/L 6PPD exhibited dose-dependent reductions in melanin deposition, suppressed tyrosinase activity and downregulation of melanogenesis-related genes ( tyr , mitfa , trp1 , trp2 , and dct ). Notably, the inhibition of tyrosinase activity was closely linked to behavioral impairments, as larvae exposed to 100 μg/L 6PPD showed significantly decreased swimming distance and velocity under light-dark cycles. Molecular docking revealed strong binding affinities between 6PPD and the key melanogenic proteins (Dct, Tyr, Tyrp1a, and Tyrp1b), suggesting direct interference with enzymatic function. Parallel experiments in B16F10 cells confirmed cross-species melanin suppression, with reduced gene expression and melanin synthesis-related protein (Mitfa and Tyr) at subtoxic concentrations (0.5 and 2.5 mg/L), which was also verified by Masson-Fontana staining. These findings demonstrated that 6PPD disrupted conserved melanogenic pathways by targeting enzymatic activity, posing ecological risks to aquatic and terrestrial organisms.
研究领域:
毒理学
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发育生物学
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环境科学
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生物化学
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药理学
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分子生物学
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DOI
PubMed
高影响因子
PROCESS BIOCHEMISTRY
·
2021
·
IF 3.757
Yonghua Hu,Yuan Zhou,Xiaohua Hu,Qiaoling Chen,Yan Shi,Jiangxing Zhuang,Qin Wang
Cefotaxime sodium (CTX) was found to inhibit the activity of mushroom tyrosinase. The present study was conducted to investigate its inhibition of melanogenesis in B16F10 cells. CTX was found to inhibit melanin synthesis in B16F10 cells at a concentrations less than 200 μmol/L with no cytotoxicity. CTX reduced tyrosinase activity in a dose-dependent manner. CTX inhibited melanin formation from the results of the Masson-Fontana melanin staining and transmission electron microscope CTX influenced melanin production by influencing the expression of the proteins MITF, TRP-1, TRP-2 and TYR. Furthermore, CTX could down-regulate the intracellular cAMP/PKA/CREB contents, affecting the expression of MITF, and further down-regulate the expression of TRP-1, TRP-2 and TYR to inhibit melanin. Furthermore, CTX has been shown to inhibit body pigmentation in zebrafish. These results may provide a theoretical foundation for the new application of CTX in the field of medicine.
研究领域:
药理学
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细胞生物学
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分子生物学
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DOI
高影响因子
PROCESS BIOCHEMISTRY
·
2019
·
IF 2.883
Yu-Xia Wang,Wei-Chao Su,Qin Wang,Yu-Feng Lin,Yuan Zhou,Long-Fang Lin,Su Ren,Yan-Ting Li,Qing-Xi Chen,Yan Shi
In this study, the antityrosinase and antioxidant activities of four guanidine compounds (GCs), including guanylthiourea (GT), guanidine thiocyanate (GTC), phenylguanidine (PG), and phenethyldiguanide (PTDG), were investigated. The results showed that the GCs reduced the monophenolase and diphenolase activities of tyrosinase. The IC 50 values of GT, GTC, PG, and PTDG were 0.27, 3.53, 6.68, and 5.18 mM for monophenolase and 0.23, 3.24, 3.97 and 2.50 mM for diphenolase, respectively. The inhibition of diphenolase activity was reversible for the four GCs. The inhibition types of GT and PTDG were competitive, while those of GTC and PG were mixed. FRAP, ABTS, DPPH, and DNA damage protection assays revealed that only GT possessed significant antioxidant activity. Furthermore, GT was found to decrease the melanin content and expression of TYR, MITF and DCT in both B16F10 cells and zebrafish. Overall, our results indicated that GT can inhibit tyrosinase activity in vitro , which suggests that these GCs are potential candidates for novel small-molecule tyrosinase inhibitors and that GT could have broader application prospects.
研究领域:
药理学
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生物化学
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细胞生物学
·
分子生物学
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产品关联
DOI
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2023
·
IF 6.1
Yi-Chi Chen,Yang-Yang Liu,Liqiang Chen,Dong-Mei Tang,YunLi Zhao,Xiao-Dong Luo
Plumula Nelumbinis, the green embryo of a lotus seed, is widely consumed in China as a well-known food with medicinal effects. In this study, 14 alkaloids, including 4 new and 10 known alkaloids, were isolated from it, which were elucidated by comprehensive spectroscopic analysis, and were investigated for their antimelanogenic effects in vitro and in vivo. As a result, melanogenesis in α-MSH-stimulated B16F10 cells was reduced significantly by a new compound 4 and known compound 12 at a concentration of 0.5 μg/mL, and the tyrosinase (TYR) activities were inhibited by 78.7 and 82.0% at 4 μg/mL, prior to α-arbutin (41.3%). Additionally, compounds 4 and 12 also exhibited superior antimelanogenic effects compared to α-arbutin on a zebrafish assay model at equivalent concentrations. Mechanistically, our preliminary findings suggested that compounds 4 and 12 exerted antimelanogenesis effect probably by inhibiting key proteins involved in melanin production such as microphthalmia-associated transcription factor, TYR, TRP-1, and TRP-2. The findings highlight the potential use of Plumula Nelumbinis containing compounds 4 and 12 as functional foods for treating hyperpigmentation.
研究领域:
药理学
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生物化学
·
药物化学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Oncology
·
2025
·
IF 3.3
Qi Ouyang,Shengye Tian,Hengyu Zhou,Ying Mao,Xiang Li,Feng Yan,Ailong Liu,Xiang Hu,Changqiao You,Jun He
Background Melanomas are caused by the malignant transformation of melanocytes. Numerous studies have demonstrated that the tyrosol components of salidroside inhibit tyrosinase activity. The PI3K/Akt/mTOR signaling pathway plays a crucial role in biological pigment synthesis. However, how salidroside achieves its anti-melanoma effect in melanoma by regulating PI3K/Akt/mTOR remains poorly understood. This study aimed to explore the effect of salidroside on PI3K/Akt/mTOR in melanoma, which plays a role in regulating melanogenesis. Methods Network pharmacology was predicted that salidroside may exert an anti-melanoma effect through modulating melanin synthesis functions and signaling pathways. Zebrafish whole-embryo in situ hybridization, RT-qPCR, melanin synthesis and tumorigenesis assays, and were performed to investigate the therapeutic efficacy of salidroside in melanin synthesis. The mechanism of salidroside in anti-melanoma activity was examined by RT-qPCR, Western blot, immunofluorescence, in vivo imaging, immunohistochemistry. Results We confirmed salidroside may exert an anti-melanoma effect through modulating melanin synthesis-related gene expression and PI3K/Akt pathway by Network pharmacology. Furthermore, salidroside slowed melanin synthesis in zebrafish embryos and H 2 O 2 -induced B16F10 cells by inhibited oxidative stress. Moreover, we determined the effect of salidroside on anti-melanin synthesis via PI3K/Akt/mTOR pathway in vitro , and western blot results showed that salidroside increased the expression of Nrf2 in the nucleus, as well as inhibited the phosphorylation of mTOR and PI3K/Akt pathway. Finally, intratumoral administration showed salidroside suppressed melanoma growth. Conclusion Salidroside inhibits melanin synthesis and melanoma development most likely by its antioxidant properties and downregulating the PI3K/Akt/mTOR pathway. Our results may provide a novel therapeutic strategy for the treatment of melanoma.
研究领域:
肿瘤学
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药理学
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生物化学
·
细胞生物学
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分子生物学
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皮肤病学
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生物医学研究
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产品关联
DOI
PubMed
高影响因子
PROTEIN JOURNAL
·
2021
·Vol. 40
·期 5
·709-720
·
IF 2.371
Jiang Xuan,Zhang Xin,Fu Chao,Zhao Ruili,Jin Tianming,Liu Mengyue,Pan Chenhao,Li Liu An,Ma Jifei,Yu Enyuan,YU Xiaoxue,Hu Ye
Malignant melanoma, an increasingly common form of skin cancer, poses a significant threat to public health, especially when the disease progresses past skin lesions to the stage of advanced metastasis. In this work, a new anti-tumor peptide, temporin La (T-La), was selected from a cDNA library generated from bullfrog skin. Two new derivative antitumor peptides, T-La (S) and T-La (FS), were designed by bioinformatics analysis and coupled with the RGD small molecule peptide to create chimeric RGD peptides, (RGD-T-La [S] and RGD-T-La [FS]). Preliminary experiments showed that the new antitumor peptides had significant antitumor effects. After coupling to the chimeric RGD peptide, the targeted treatment of mouse melanoma was significantly improved. Our data demonstrate that the 4 peptides tested herein significantly inhibited the proliferation, migration, and invasion of B16F10 cells; with an increase in polypeptide concentration, the proportion of melanoma cells in the G0/G1 phase decreased or increased significantly, respectively, the reactive oxygen species (ROS) content increased significantly, the mitochondrial membrane potential decreased significantly, and the expression of pro-apoptotic Bax, Caspase-3, and Caspase-9 increased, and anti-apoptotic Bcl-2 decreased significantly. Tyr and MITF genes were significantly downregulated. In conclusion, the use of these new anti-tumor peptides, when combined with a chimeric RGD peptide, may increase ROS levels and decrease mitochondrial membrane potential by inhibiting the activity of mitochondria, thus releasing apoptosis-promoting factors in B16F10 cells. The present study describes a new potential strategy for the application of promising peptides in the treatment of various cancers.
研究领域:
肿瘤学
·
药理学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2023
·Vol. 24
·期 4
·3859
·
IF 5.6
Jingyi Zhu,Xiangning Li,Wenling Gao,Jian Jing
Malignant melanoma, an increasingly common form of skin cancer, is a major threat to public health, especially when the disease progresses past skin lesions to the stage of advanced metastasis. Targeted drug development is an effective strategy for the treatment of malignant melanoma. In this work, a new antimelanoma tumor peptide, the lebestatin–annexin V (designated LbtA5) fusion protein, was developed and synthesized by recombinant DNA techniques. As a control, annexin V (designated ANV) was also synthesized by the same method. The fusion protein combines annexin V, which specifically recognizes and binds phosphatidylserine, with the disintegrin lebestatin (lbt), a polypeptide that specifically recognizes and binds integrin α1β1. LbtA5 was successfully prepared with good stability and high purity while retaining the dual biological activity of ANV and lbt. MTT assays demonstrated that both ANV and LbtA5 could reduce the viability of melanoma B16F10 cells, but the activity of the fusion protein LbtA5 was superior to that of ANV. The tumor volume growth was slowed in a mouse xenograft model treated with ANV and LbtA5, and the inhibitory effect of high concentrations of LbtA5 was significantly better than that of the same dose of ANV and was comparable to that of DTIC, a drug used clinically for melanoma treatment. The hematoxylin and eosin (H&E) staining test showed that ANV and LbtA5 had antitumor effects, but LbtA5 showed a stronger ability to induce melanoma necrosis in mice. Immunohistochemical experiments further showed that ANV and LbtA5 may inhibit tumor growth by inhibiting angiogenesis in tumor tissue. Fluorescence labeling experiments showed that the fusion of ANV with lbt enhanced the targeting of LbtA5 to mouse melanoma tumor tissue, and the amount of target protein in tumor tissue was significantly increased. In conclusion, effective coupling of the integrin α1β1-specific recognition molecule lbt confers stronger biological antimelanoma effects of ANV, which may be achieved by the dual effects of effective inhibition of B16F10 melanoma cell viability and inhibition of tumor tissue angiogenesis. The present study describes a new potential strategy for the application of the promising recombinant fusion protein LbtA5 in the treatment of various cancers, including malignant melanoma.Keywords:malignant melanoma;annexin V;lebestatin;antitumor
研究领域:
肿瘤学
·
药理学
·
分子生物学
·
癌症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）