Biomedicines
·
2023
·Vol. 11
·期 9
·2442
·
IF 4.7
Eun-Young Choi,Eun-Ji Han,Su-Ji Jeon,Sang-Woo Lee,Jun-Mo Moon,Soo-Hyun Jung,Ji-Youn Jung
Oral cancer is a malignant tumor that primarily affects areas such as the lips, tongue, buccal mucosa, salivary gland, and gingiva and has a very high malignancy. Piperlongumine (PL), isolated from long pepper (Piper longumL.), is a natural alkaloid with pharmacological effects, such as anti-inflammatory and anti-atherosclerotic effects. The effect and mechanism of PL in oral cancer cell lines has not been explored. Therefore, this study aimed to investigate the mechanism of anticancer effects of PL in the human oral cancer cell lines MC-3 and HSC-4 in vitro. This study demonstrated that PL inhibits cell proliferation by inducing apoptosis and autophagy in human oral cancer cell lines, which was confirmed by the levels of apoptosis- and autophagy-related proteins through Western blotting. Moreover, the pharmacological blockade of autophagy activation by hydroxychloroquine (HCQ), an autophagy inhibitor, significantly improved PL-induced apoptosis in MC-3 cells, suggesting a cytoprotective effect. In addition, activation of the mitogen-activated protein kinase (MAPK) signaling pathway contributed to PL-induced apoptosis. Collectively, the study suggested that combining an autophagy inhibitor with PL treatment can exert effective anticancer properties in oral cancer cells by inducing apoptosis and cytoprotective autophagy via the JNK-mediated MAPK pathway.Keywords:piperlongumine;oral cancer;apoptosis;autophagy;MAPK pathway;anti-cancer agent
研究领域:
肿瘤学
·
药理学
·
细胞生物学
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DOI
PubMed
高影响因子
Nanoscale
·
2019
·Vol. 12
·期 3
·1389-1396
·
IF 6.97
Yuan Zhuang,Longjie Li,Liandong Feng,Shuangshuang Wang,Huimin Su,Haijuan Liu,Hongmei Liu,Yuzhou Wu
Selenium nanoparticles (SeNPs) can induce reactive oxygen species (ROS)-mediated cell death when accumulated in cancer cells, while rendering anti-oxidation and cancer prevention in healthy tissues at low doses. Although they are promising anticancer agents with fewer side effects, their application is limited by their relative low toxicity to cancer cells. Therefore, we propose a mitochondrion-targeting strategy to improve their cancer cell killing efficiency. Such mitochondrion-targeted SeNPs could efficiently increase ROS production and mitochondrion damage in cancer cells; however, only a slightly increased toxicity to normal cells was observed, indicating a potentially better therapeutic window for anticancer treatments.
研究领域:
纳米技术
·
肿瘤学
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MICROCHIMICA ACTA
·
2017
·Vol. 184
·期 11
·4305-4312
·
IF 4.58
Jiang Guoyi,Zhu Wanying,Shen Xin,Xu Lei,Li Xiaoxu,Wang Rui,Liu Chunyu,Zhou Xuemin
The authors describe a new kind of adenosine triphosphate (ATP) assay. It is based on the use of gold nanoparticles (AuNPs) coated with 4-mercaptophenylboronic acid (MPBA) as the recognition element for ATP. MPBA has a specific affinity for AuNPs through Au-S interaction, and three boronic acid groups undergo condensation to form a boroxine ring. This induces the aggregation of AuNPs and a visible color change from red to blue. However, in the presence of ATP, the boronic acid group of MPBA preferentially binds to the 2’, 3’-hydroxy group of ATP to form a stable boronate ester. Hence, the aggregation of AuNPs is progressively decreased as the concentration of ATP increases, and the color change is increasingly reversed. The ratio of absorbance at 520 and 683 nm increases linearly in the 8 to 100 μM ATP concentration range, with a 0.12 μM limit of detection (at an S/N ratio of 3 σ). The colorimetric assay was successfully applied to the determination of ATP in T47D breast cancer cells and in cultured cells with added anticarcinogen.
Schematic of a colorimetric assay for the visualization and sensitive and selective detection of adenosine triphosphate (ATP) based on the use of gold nanoparticles (AuNPs) coated with 4-mercaptophenylboronic acid (MPBA). The assay was applied to the determination of ATP in T47D breast cancer cells and in cultured cells with added anticarcinogen.
研究领域:
分析化学
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纳米技术
·
生物化学
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DOI
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
·
2021
·
IF 4.384
Mingyu Liu,Zhixing Lai,Lijun Zhu,Xin Ding,Xiyang Tong,Zhen Wang,Qirui Bi,Ninghua Tan
At present, oral chemotherapy showing the advantages of non-invasiveness, convenience, and high patient compliance, is gradually replacing traditional intravenous chemotherapy to treat patients with cancer. RA-XII, a unique natural cyclopeptide , exhibits various biological activities , such as anti-tumor, anti-angiogenic, and anti-metastatic activities. Designing an orally available formulation of RA-XII is of great importance in the development of clinically useful anticancer agents . However, RA-XII shows low oral bioavailability in rats due to its poor solubility and low permeability. To overcome these limitations, in this work, a natural deep eutectic solvent (NADES) was designed to efficiently deliver RA-XII by oral administration. A novel NADES composed of betaine and mandelic acid in the molar ratio of 1:1 (Bet-Man NADES) was successfully prepared based on a binary phase diagram of Bet and Man. Acute toxicity studies indicated that Bet-Man NADES was well tolerated with acceptable toxicity. In Bet-Man NADES solutions, the solubility of RA-XII was increased by up to 17.54-fold, and the diffusion and permeability of RA-XII carried out in a Franz cell was also significantly improved 10.35 times. In terms of biopharmaceutical classification this is translated into a change for RA-XII from class IV to class II systems. More importantly, Bet-Man NADES was transferred into the solid formulation by the inclusion of a polymer, and amorphous solid dispersions based on Bet-Man NADES (PVP K30/NADES/RA-XII, ASDs) were successfully prepared to improve uniformity, apparent solubility, dissolution, and cytotoxicity in vitro. Consequently, the oral bioavailability of RA-XII in NADES solutions and ASDs was enhanced by approximately 11.58 and 7.56 times compared with that of pure RA-XII in 0.5% CMC Na. Thus, it can be seen that a natural deep eutectic solvent and its modified amorphous solid dispersions are appropriate novel strategies for improving dissolution rate and bioavailability of poor soluble natural products such as RA-XII.
研究领域:
药剂学
·
肿瘤学
·
药物化学
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产品关联
DOI
PubMed
高影响因子
Results in Chemistry
·
2025
·
IF 4.2
Basharat Ali,Muhammad Riaz,Ajmal Khan,Nadir Rasheed,Muhammad Masood,Ali Iftikhar,Amir Faisal,Sobia Ahsan Halim,Jalal Uddin,Afnan Jan,Ahmed Al-Harrasi
Carbothioamides exhibit many biological properties, including antiviral, antibacterial and anticancer activities. Their ability to interfere with DNA synthesis is mainly responsible for their anticancer activities. Here, twelve phenyl-substituted carbothioamides ( 2−13 ) were synthesized and characterized using Electron Ionization Mass Spectrometry (EI-MS), proton and carbon-13 nuclear magnetic resonance ((Singhal et al., 2013 [ 1 ] ) HNMR, and 13 C NMR), Infrared (IR), and elemental analysis. The anticancer activity of the carbothioamide derivatives ( 2–13 ) was measured in the HCT116 colorectal cancer cell line by means of a three day sulforhodamine B (SRB) proliferation assay. Among the series, four compounds ( 2 , 4 , 11 , and 12 ) which inhibited the cell viability by more than 50 % at 50 μM concentration. IC 50 determination of these four compounds revealed 1-benzoyl-4-(2-bromophenyl) thiosemicarbazide ( 11 ) as the most potent compound with IC 50 values of 21.61 ± 4.77 μM, 18.34 ± 3.53 μM and 17.87 ± 12.02 μM in the breast cancer (MCF-7) cell line, human colorectal carcinoma (HCT116) cell line and MD Anderson-metastatic breast (MDA-MB-453) cell lines respectively. Prolonged treatment of cells with the compound resulted in apoptotic cell death as determined by cleavage of Poly (ADP-ribose) polymerase (PARP), a caspase 3 substrate and an apoptotic marker. This study, therefore, explored novel derivatives of carbothioamides for their anticancer activities; the structure activity relationship (SAR) reported in this study and predicted docking analysis and ADMET profile will help optimize carbothioamides as anticancer agents.
研究领域:
药物化学
·
药理学
·
肿瘤学
·
生物化学
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分子生物学
✓ 已验证
产品关联
DOI
高影响因子
Scientific Reports
·
2018
·Vol. 8
·期 1
·1-13
·
IF 4.122
Cheng Xingan,Ye Jingmin,He Huiqing,Liu Zhanmei,Xu Chunbao (Charles),Wu Bo,Xiong Xialing,Shu Xugang,Jiang Xuhong,Qin Xiangjing
Matrine is a traditional Chinese medicine and botanical pesticide with broad biological activities, including pharmacological and agricultural activities. In present work, two matrine derivatives have been successfully synthesized via introducing indole and cyclohexylamino to 13 position of matrine, respectively, with sophocarpine as starting material, and structurally characterized via infrared spectroscopy(IR), MS, 1 H NMR, 13 C NMR and X-ray crystal diffraction. The results of the in vitro biological activity tests showed that these two matrine derivatives exhibited even better activities against human cancer cells Hela229 and insect cell line Sf9 from Spodoptera frugiperda (J. E. Smith) than that of parent matrine, suggesting that the heterocyclic or cyclic group can dramatically increase the biological activity of matrine. It is worth to mention that 13-indole-matrine could possibly inhibit the growth of insect cells or human cancer cells by inducing cell apoptosis. The results of the present study provide useful information for further structural modifications of these compounds and for exploring new, potent anti-cancer agents and environment friendly pesticides.
研究领域:
药理学
·
农业科学
·
分子生物学
·
有机化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MEDICINAL CHEMISTRY RESEARCH
·
2018
·Vol. 28
·期 2
·133-142
·
IF 1.607
Feng Yu,Teng Xingxing,Gu Jinhua,Yu Bangwei,Luo Yan,Ye Lianbao
In the previous research, our group designed and synthesized 2,3,4,5-tetrahydro-1 H -pyrido-[4,3-b] indoles, which showed high anti-tumor activity. In this study, a series of novel 2,3,4,5-tetrahydro-1 H -pyrido-[4,3-b] indole derivatives were designed by introducing an alkyl or aralkyl and a sulfonyl group, which are considered as the pharmacophores of some antitumor drugs based on the combination principles, and synthesized. The antiproliferative activity of all the target compounds were evaluated against Hela, A549, HepG2, and MCF-7 cell lines using the MTT assay in vitro. The results were represented by IC 50 values. All compounds showed moderate to excellent antiproliferative activity with IC 50 values between 0 μM and 100 μM against cancer cells. The proliferations of Hela, A549, HepG2, and MCF-7 cell lines were inhibited in a dose-dependent manner, and the cytolytic activity was markedly inhibited at the same time. The IC 50 values of intermediate 3 inhibited against Hela, A549, HepG2, and MCF-7 cell lines were 52.75, 50.30, 60.31, and 54.39 μM, respectively, which were higher than the new compounds that we expected. The compounds 4a – 4d bearing sulfonyl, substituted by electron donating group, showed moderate to significant antiproliferative activity, in which compound 4c was the best with the IC 50 values of 13.71, 9.42, 15.06, and 14.77 μM, and these results suggested that the introduction of sulfonyl could increase the antiproliferative activity of 2,3,4,5-tetrahydro-1 H -pyrido-[4,3-b]indole. Compounds 4e – 4g bearing alkyl, phenyl, and arylated alkyl produced good antiproliferative activity and the IC 50 value of 4 g was lower than 30 μM. The target compounds were more potent against A549 compared to the other three cell lines. Molecular docking studies revealed the binding orientations of all the synthesized compounds in the active site of c-Met. Moreover, molecular dynamics simulations have been performed to evaluate the binding stabilities between the synthesized compounds and their receptors.
研究领域:
药物化学
·
肿瘤学
·
计算生物学
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DOI
高影响因子
JOURNAL OF BIOMATERIALS APPLICATIONS
·
2017
·
IF 2.31
Liangping Li,Ruisong Tao,Mingming Song,Yue Zhang,Kuanmin Chen,Hui Wang,Renmin Gong
In this paper, the starch was firstly modified by quaternary reagent to obtain cationic starch. Then self-assembled folate–biotin-quaternized starch nanoparticles were prepared by a one-pot synthesis via N,N′-dicyclohexylcarbodiimide/N-hydroxysuccinimide/4-dimethylaminopyridine-mediated esterification reaction. The physicochemical properties of the prepared folate–biotin-quaternized starch nanoparticles were characterized. The average diameter of folate–biotin-quaternized starch nanoparticles was 109 nm with polydispersity index of 0.183 and zeta potential of 28.59 mV. The folate–biotin-quaternized starch nanoparticles were used as co-carrier of siRNA and doxorubicin with satisfactory drug loading capacity (6.98%) and encapsulation efficiency (69.66 %), and siRNA could be efficiently encapsulated at 40/1 weight ratio of doxorubicin/folate–biotin-quaternized starch nanoparticles to siRNA. The folate–biotin-quaternized starch nanoparticles could effectively protect siRNA from degradation of serum RNAase for up to 48 h. The release characteristics of doxorubicin and siRNA from folate–biotin-quaternized starch nanoparticles were studied in different pH environment and the release behaviors of two drugs were all pH sensitive. The folate–biotin-quaternized starch nanoparticles as a potential co-carrier of anticancer agents and gene drugs was expected to achieve future practical application in vitro and in vivo.
研究领域:
药剂学
·
纳米技术
·
癌症研究
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
CHEMISTRY & BIODIVERSITY
·
2018
·Vol. 15
·期 4
·e1800024
·
IF 1.617
Qi-Zhe Gong,Di Xiao,Feng Feng,Xiao-Dong Wen,Wei Qu
ent -Sauchinone, a lignan isolated from Saururus chinensis ( Lour .) Baill ., was reported that it could modulate the expression of signal transducer and activator of transcription 3 (STAT3). Since STAT3 plays a key role in invasion, migration, and metastasis of cancer, we investigated whether ent -sauchinone could exert promising inhibitory effects on the invasion and migration of the metastatic human liver cancer cell line SMMC-7721 in the present study. ent -Sauchinone was extracted from dried herbs of Saururus chinensis ( Lour .) Baill . Human liver cancer cell lines SMMC-7721 and HCCLM3 were used to test the effect of ent -sauchinone on cell viability. The IC 50 values and time-dependent effect of ent -sauchinone were determined by MTT assay. Cell migration and invasion of SMMC-7721 were evaluated by the wound healing test and transwell assay respectively, the known anti-metastasis agent curcumin was used as a positive control. Western blotting assay was used to investigate relevant molecular mechanisms of cell invasion and migration. Though ent -sauchinone didn't show high cytotoxicity, the wound healing assay and transwell migration assay revealed a profound impairment in the metastatic potential of SMMC-7721 cells due to down-regulation of N-cadherin, MMP-2, and MMP-9 proteins induced by inhibiting the phosphorylation of STAT3. These findings suggest that ent -sauchinone could be used as a promising agent to treat cancer metastasis.
研究领域:
肿瘤学
·
药理学
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NEW JOURNAL OF CHEMISTRY
·
2024
·
IF 2.7
Xiong-Li Liu,Shuang Chen,Xi-Rui Wang,Wei-Na Wang,Ke-Lan Xu,Pan Hu,Ying Zhou,Bo-Wen Pan,Qi-Lin Wang
Here, we demonstrate that the first example of harmaline scaffolds serving as acceptor/acceptor-based N-C-C synthons-triggered the ring opening and skeletal reconstruction of 3-vinyl benzofuranones for the construction of a library of skeletally-diverse polycyclic harmaline scaffolds. These products were smoothly afforded in up to 77% yield, >20:1 dr under catalyst-free conditions, and expanded the chemical space of biologically significant harmaline derivative species. All synthetic compounds showed cytotoxic activity against tumor cells, especially the compound 3at, which exhibited selective cytotoxicity against A549 cells and lower cytotoxicity against normal cells MRC-5 and HK-2. In further mechanism research, 3at inhibited A549 cell proliferation through the G1 phase arrest, induced A549 cell apoptosis through internal and external apoptosis pathways, and suppressed the migration and invasion abilities of A549 cells. These data indicated that compound 3at is the most effective compound in the series and can serve as a promising precursor for drug development.
研究领域:
药物化学
·
肿瘤学
·
药学
✓ 已验证
产品关联
DOI
高影响因子
NEW JOURNAL OF CHEMISTRY
·
2022
·Vol. 46
·期 40
·19442-19454
·
IF 3.925
Zhi-Gang Yin,Xiong-Wei Liu,Lin Chen,Xiong-Li Liu,Bo-Wen Pan,Ying Zhou
A substrate-dependent, highly β-regioselective one-pot multicomponent 1,3-dipolar cycloaddition reaction of 3-methyl-4-nitro-5-isatylidenyl-isoxazoles with azomethine ylides (thermally generated in situ from ninhydrin and sarcosine) is reported for the first time, furnishing a library of biologically useful bispiro[oxindole-isoxazole-indandione] hybrids. Target novel and structurally complex compounds have been obtained in good yields and diastereoselectivities (up to 91% yield and 20 : 1 dr) with two adjacent spiro quaternary centres. Furthermore, the described method, which is different from our previous work of α-regioselective cycloaddition of 3-methyl-4-nitro-5-isatylidenyl-isoxazoles, is a highly β-regioselective cycloaddition. The newly synthesized compounds potently inhibited the proliferation of various cancer cell lines. The most potent compound 4ah could induce the apoptosis of K562 cells through a caspase-dependent and -independent pathway.
研究领域:
有机化学
·
药物化学
·
癌症研究
✓ 已验证
产品关联
DOI
高影响因子
Journal of Materials Chemistry B
·
2019
·Vol. 8
·期 4
·655-665
·
IF 5.047
Zhanxia Zhang,Wei Cheng,Yongfu Pan,Lijun Jia
Stimuli response or controlled release is a new research hotspot in nanomedicine; however, there is scarce research on organic nanomedicines with stimuli responses, which limits their practical biological applications. In addition, homoharringtonine (HHT) has been used as an effective anticancer agent, but reducing its toxicity and side effects is an urgent problem to be solved. Herein, an EGFR (epidermal growth factor receptor) aptamer-modified HHT-loaded PLGA-SS-PEG nanomedicine was developed. The nanomaterial possesses spherical morphology and admirable biocompatibility. After targeted endocytosis in tumour cells via the selective recognition between EGFR and its aptamer, the PLGA nanomedicine is triggered by a high GSH level and releases its cargo in lung cancer cells. The in vitro and in vivo results reveal that the PLGA nanomedicine not only inhibited the proliferation and promoted the apoptosis of lung cancer cells, but also possessed better therapeutic efficacy and less toxic side effects compared with the free anticancer agent. Consequently, this study provides a novel approach to construct a biodegradable nanomedicine with targeted recognition and stimuli response. Moreover, it inhibited the proliferation of lung cancer cells with high efficiency and low toxicity. Importantly, the PLGA nanomedicine demonstrates encouraging potential as a multifunctional nano-system applicable for cancer therapy.
研究领域:
药学
·
纳米技术
·
癌症研究
·
生物医学工程
✓ 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）