Chinese Journal of Natural Medicines
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2014
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IF 0
De-Biao YAN,Dong-Ping ZHANG,Ming LI,Wen-Yuan LIU,Feng FENG,Bin DI,Qing-Long GUO,Ning XIE
To synthesize a series of 3-, 4-, and/or 11-trihydroxy modified bergenin derivatives and evaluated their cytotoxic activity in vitro . The phenolic hydroxyl groups of bergenin were protected by benzyl groups with benzyl bromide. Treatment of dibenzyl bergenin with the corresponding acid in the presence of EDC·HCl and DMAP in CH 2 Cl 2 , followed by hydrogenation over Pd/C catalysts, afforded derivatives of bergenin esters. All of the target compounds were identified by IR, MS, and 1 H NMR. Twenty-six novel and three known derivatives of bergenin esters were synthesized. Their cytotoxicity values were evaluated by the MTT assay on the inhibition of DU-145 and BGC-823 cells in vitro . Several triply-substituted ( 3a, 4a, 5a, 6a, 7a ) and doubly-substituted ( 8b, 9b ) bergenin derivatives exhibited higher cytotoxic activity than bergenin. The result showed that the size of substituents and the lipophilicity of the bergenin esters displayed an important role on their cytotoxic activity.
研究领域:
药物化学
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肿瘤学
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DOI
PubMed
Oncology Letters
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2018
·Vol. 15
·期 5
·7993-7998
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IF 1.664
Hai‑Bo Yang,Hui‑Ru Gao,Yuan‑Jing Ren,Fei‑Xiang Fang,Hong‑Tao Tian,Zhen‑Jiang Gao,Wei Song,Shao‑Min Huang,An‑Fang Zhao
Resistance to apoptosis is an characteristic of cancer cells that serves a critical function in tumor development and represents a target for antitumor therapy. Isoimperatorin (ISOIM), a coumarin compound, exhibits antitumor functions in multiple types of tumor cells. However, its antitumor effects and molecular mechanisms with respect to gastric cancer have not been elucidated. The present study assessed the anti‑proliferative and apoptotic effects of ISOIM on human BGC‑823 gastric cancer cells and elucidated its underlying molecular mechanisms. Cell proliferation was evaluated using MTT assays. Analysis of cell morphology was performed by hematoxylin and eosin, Hoechst 33258 and acridine orange/ethidium bromide staining. In addition, cell cycle and apoptosis was evaluated using flow cytometry analysis; expression of apoptosis‑associated proteins was studied by western blotting. The results of the present study revealed that ISOIM significantly inhibited cell proliferation by arresting the cell cycle at the G2/M phase and induced apoptosis by increasing Bcl‑2‑associated X (Bax) expression with a concomitant decrease in Bcl‑2 expression, resulting in a decreased Bcl‑2/Bax ratio compared with the control. In addition, ISOIM treatment also resulted in cytochrome c translocating from the mitochondria to the cytosol. Furthermore, caspase‑3 was significantly activated in response to treatment with ISOIM, suggesting that apoptosis in BGC‑823 cells is induced in the mitochondrial pathway. Taken together, the results of the present study indicate that ISOIM may significantly induce apoptosis in BGC‑823 cells and that the pro‑apoptotic mechanisms of ISOIM could be associated with the mitochondrial pathway.
研究领域:
肿瘤学
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分子生物学
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药理学
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DOI
PubMed
高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
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2023
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IF 7.3
Xing-Jie Dai,Li-Juan Zhao,Long-Hua Yang,Ting Guo,Lei-Peng Xue,Hong-Mei Ren,Zhi-Li Yin,Xiao-Peng Xiong,Ying Zhou,Shi-Kun Ji,Hui-Min Liu,Hong-Min Liu,Ying Liu,Yi-Chao Zheng
Histone lysine specific demethylase 1 (LSD1) has been recognized as an important epigenetic target for cancer treatment. Although several LSD1 inhibitors have entered clinical trials, the discovery of novel potent LSD1 inhibitors remains a challenge. In this study, the antipsychotic drug chlorpromazine was characterized as an LSD1 inhibitor (IC50 = 5.135 μM), and a series of chlorpromazine derivatives were synthesized. Among them, compound 3s (IC50 = 0.247 μM) was the most potent one. More importantly, compound 3s inhibited LSD1 in the cellular level and downregulated the expression of programmed cell death-ligand 1 (PD-L1) in BGC-823 and MFC cells to enhance T-cell killing response. An in vivo study confirmed that compound 3s can inhibit MFC cell proliferation without significant toxicity in immunocompetent mice. Taken together, our findings indicated that the novel LSD1 inhibitor 3s tethering a phenothiazine scaffold may serve as a lead compound for further development to activate T-cell immunity in gastric cancer.
研究领域:
肿瘤学
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免疫学
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药理学
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产品关联
DOI
PubMed
高影响因子
Food Bioscience
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2019
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IF 3.22
Chun-Min Ma,Tie-Jing Li,Xin-Huai Zhao
Lactoferrin hydrolysates (LF-H) were digested using pepsin and modified using a pepsin-catalyzed plastein reaction with tryptophan (Trp) to obtain a target product. LF-H, the target product, plastein reaction-modified LF-H alone, and a mixture of LF-H and Trp were evaluated for their activities with human gastric cancer BGC-823 cells at 24 and 48 h. Assay results indicated that the target product had decreased free amino groups and had incorporated Trp. LF-H and the plastein reaction-modified LF-H alone did not show detectable growth inhibition on BGC-823 cells at 1–3 mg/mL; however, the target product at the same dose levels inhibited cell growth, and showed higher activity than the mixture ( P < 0.05). The target product at 2 and 3 mg/mL stopped cell cycle progression at the G0/G1-phase, induced DNA fragmentation , and showed apoptosis induction, which increased the number of apoptotic cells. Moreover, time- and dose-dependent responses were observed in these experiments. RT-PCR assay results indicated that exposure of the cells to the target product resulted in up- and down-regulated mRNA expression for 7 apoptosis-related genes, namely Bcl-2, Bcl-xl, Bad, Bax, caspase-3, caspase-6, and caspase-9. Thus, the plastein reaction increased in vitr o anticancer activities of LF-H with BGC-823 cells, and more importantly, both the plastein reaction and Trp incorporation contributed to enhanced activities.
研究领域:
生物化学
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癌症研究
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分子生物学
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产品关联
DOI
高影响因子
ANTI-CANCER DRUGS
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2019
·Vol. 30
·期 1
·46-55
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IF 1.801
Lin Fuxing,Yang Jie,Muhammad Umair,Sun Jing,Huang Zhenghua,Li Wei,Lv Fengxia,Lu Zhaoxin
Bacillomycin D can inhibit the growth of Aspergillus ochraceus in food samples. In addition, it can induce apoptosis in and inhibit the proliferation of cancer cells, although the details of this mechanism are unknown. In this study, we separated bacillomycin D-C14, D-C15, D-C16
monomers from the Bacillus subtilis strain fmbJ. The bacillomycin D monomers containing longer fatty acid chains better induced apoptosis in Bgc-823, Sgc-7901, and Hgc-27 gastric cancer cells. The Bgc-823 cell line was the most sensitive. Acridine orange-ethidium bromide staining indicated
that bacillomycin D-C16-induced Bgc-823 cell death by triggering apoptosis, characterized by membrane blebbing, cellular shrinkage, and DNA fragmentation. Flow cytometric analysis showed a bacillomycin D-C16 dose-dependent trigger of Bgc-823 apoptosis. Bacillomycin D-C16-induced the mitochondrial
pathway, as indicated by a reduced Bcl-2/Bax expression ratio, enhanced cytochrome C release, and higher levels of cleaved caspase-3. Furthermore, bacillomycin D-C16 effectively repressed phosphorylation of the serine–threonine protein kinase Akt at Ser-473 and increased the levels of
the FoxO3a protein. The combination of the PI3K/Akt-inhibitor BEZ235 with bacillomycin D-C16 enhanced the apoptosis of Bgc-823 cells. Together, these findings indicated that bacillomycin D-C16 induces apoptosis through the PI3K/Akt and FoxO3a signaling pathways.
研究领域:
肿瘤学
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分子生物学
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细胞生物学
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药理学
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DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
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2022
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IF 5.364
Boyang Cheng,Xindang Chu,Ruiwen Liu,Xinyuan Ma,Mengyang Wang,Jiayi Zhang,Pingxuan Jiao,Qianqian Gao,Wenxiao Ma,Yongmin Zhang,Chuanke Zhao,Demin Zhou,Sulong Xiao
Betulinic acid (BA) and oleanolic acid (OA) are plant-derived conjugates found in various medicinal plants that have emerged as potential antitumor agents. Herein, a series of novel BA and OA derivatives were synthesized by conjugation with per-O-methylated-β-cyclodextrin (PM-β-CD), and their anticancer properties against a panel of three human cancer cell lines were evaluated. Two OA-PM-β-CD conjugates (48 and 50) were observed to be the most potent conjugates against the three cell lines (MCF-7, BGC-823, and HL-60), with a 15- to 20-fold decrease in the IC50 values (IC50: 6.06–8.47 μM) compared with their parental conjugate (OA). Annexin V-FITC/propidium iodide staining and Western blot analysis revealed that both conjugates induced apoptosis in HL-60 cells. Additionally, in the representative conjugate 48-treated HL-60 cells, a decrease in mitochondrial membrane potential and subsequent release of cytochrome c into the cytosol were observed, indicating the activation of the intrinsic apoptosis pathway. Furthermore, 48 dramatically induced the generation of reactive oxygen species (ROS) in HL-60 cells, and the corresponding effect could be reversed using the ROS scavenger N-acetylcysteine. Collectively, these results suggest that the novel pentacyclic triterpenoid derivatives trigger the intrinsic apoptotic pathways via the ROS-mediated activation of caspase-3 signaling, inducing cell death in human cancer cells.
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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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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