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A Series of New Ligustrazine-Triterpenes Derivatives as Anti-Tumor Agents: Design, Synthesis, and Biological Evaluation.

Xu B, Chu F, Zhang Y, Wang X, Li Q, Liu W, Xu X, Xing Y, Chen J, Wang P, Lei H - Int J Mol Sci (2015)

Bottom Line: A combination of fluorescence staining observation and flow cytometric analysis indicated that 4a could induce HepG2 cell apoptosis.Further studies suggested that 4a-induced apoptosis is mediated through depolarization of the mitochondrial membrane potential and increase of intracellular free Ca2+ concentration.In addition, the structure-activity relationships of these derivatives were briefly discussed.

View Article: PubMed Central - PubMed

Affiliation: School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, China. weichenxubing@126.com.

ABSTRACT
A series of novel ligustrazine-triterpenes derivatives was designed, synthesized and screened for their cytotoxicity against five cancer cell lines (Bel-7402, HepG2, HT-29, Hela, and MCF-7) and Madin-Darby canine kidney (MDCK). Current study suggested that most of the ligustrazine-triterpenes conjunctions showed better cytotoxicity than the starting materials. In particular, compound 4a exhibited better cytotoxic activity (IC50<5.23 μM) against Bel-7402, HT-29, MCF-7, Hela, and HepG2 than the standard anticancer drug cisplatin (DDP). The cytotoxicity selectivity detection revealed that 4a exhibited low cytotoxicity (IC50>20 μM) towards MDCK cells. A combination of fluorescence staining observation and flow cytometric analysis indicated that 4a could induce HepG2 cell apoptosis. Further studies suggested that 4a-induced apoptosis is mediated through depolarization of the mitochondrial membrane potential and increase of intracellular free Ca2+ concentration. In addition, the structure-activity relationships of these derivatives were briefly discussed.

No MeSH data available.


Related in: MedlinePlus

Morphological observation of HepG2 cells using AO/EB double staining (200×): (a) control group; (b) 2 μM; (c) 4 μM; and (d) 8 μM. The cell morphology was examined under the fluorescence microscope after AO/EB staining. The most representative fields are shown. Arrows indicate the typical apoptotic cell.
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ijms-16-21035-f004: Morphological observation of HepG2 cells using AO/EB double staining (200×): (a) control group; (b) 2 μM; (c) 4 μM; and (d) 8 μM. The cell morphology was examined under the fluorescence microscope after AO/EB staining. The most representative fields are shown. Arrows indicate the typical apoptotic cell.

Mentions: To further characterize 4a-induced HepG2 cell apoptosis, the changes in cell morphology of the treated cells were determined using AO/EB double staining. AO is a vital dye that stains both live and dead cells as it can penetrate normal cell membrane. EB stains only cells that have lost their membrane integrity. Cells that stained green indicate viable cells, yellow indicate early apoptosis and orange/red indicate late apoptosis [29,30]. As shown in Figure 4, HepG2 cells in control group appeared bright green with normal cell morphology whereas the cells treated with 4a (2, 4, 8 μM) for 72 h showed an increased number of orange- and red-stained cells in a dose dependent manner. And characteristic changes of apoptosis, including condensation and fragmentation of nucleus and formation of apoptotic bodies, were observed in the cells treated with different concentrations of compound 4a. These results confirmed that 4a significantly induced apoptosis in HepG2 cells.


A Series of New Ligustrazine-Triterpenes Derivatives as Anti-Tumor Agents: Design, Synthesis, and Biological Evaluation.

Xu B, Chu F, Zhang Y, Wang X, Li Q, Liu W, Xu X, Xing Y, Chen J, Wang P, Lei H - Int J Mol Sci (2015)

Morphological observation of HepG2 cells using AO/EB double staining (200×): (a) control group; (b) 2 μM; (c) 4 μM; and (d) 8 μM. The cell morphology was examined under the fluorescence microscope after AO/EB staining. The most representative fields are shown. Arrows indicate the typical apoptotic cell.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4613240&req=5

ijms-16-21035-f004: Morphological observation of HepG2 cells using AO/EB double staining (200×): (a) control group; (b) 2 μM; (c) 4 μM; and (d) 8 μM. The cell morphology was examined under the fluorescence microscope after AO/EB staining. The most representative fields are shown. Arrows indicate the typical apoptotic cell.
Mentions: To further characterize 4a-induced HepG2 cell apoptosis, the changes in cell morphology of the treated cells were determined using AO/EB double staining. AO is a vital dye that stains both live and dead cells as it can penetrate normal cell membrane. EB stains only cells that have lost their membrane integrity. Cells that stained green indicate viable cells, yellow indicate early apoptosis and orange/red indicate late apoptosis [29,30]. As shown in Figure 4, HepG2 cells in control group appeared bright green with normal cell morphology whereas the cells treated with 4a (2, 4, 8 μM) for 72 h showed an increased number of orange- and red-stained cells in a dose dependent manner. And characteristic changes of apoptosis, including condensation and fragmentation of nucleus and formation of apoptotic bodies, were observed in the cells treated with different concentrations of compound 4a. These results confirmed that 4a significantly induced apoptosis in HepG2 cells.

Bottom Line: A combination of fluorescence staining observation and flow cytometric analysis indicated that 4a could induce HepG2 cell apoptosis.Further studies suggested that 4a-induced apoptosis is mediated through depolarization of the mitochondrial membrane potential and increase of intracellular free Ca2+ concentration.In addition, the structure-activity relationships of these derivatives were briefly discussed.

View Article: PubMed Central - PubMed

Affiliation: School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, China. weichenxubing@126.com.

ABSTRACT
A series of novel ligustrazine-triterpenes derivatives was designed, synthesized and screened for their cytotoxicity against five cancer cell lines (Bel-7402, HepG2, HT-29, Hela, and MCF-7) and Madin-Darby canine kidney (MDCK). Current study suggested that most of the ligustrazine-triterpenes conjunctions showed better cytotoxicity than the starting materials. In particular, compound 4a exhibited better cytotoxic activity (IC50<5.23 μM) against Bel-7402, HT-29, MCF-7, Hela, and HepG2 than the standard anticancer drug cisplatin (DDP). The cytotoxicity selectivity detection revealed that 4a exhibited low cytotoxicity (IC50>20 μM) towards MDCK cells. A combination of fluorescence staining observation and flow cytometric analysis indicated that 4a could induce HepG2 cell apoptosis. Further studies suggested that 4a-induced apoptosis is mediated through depolarization of the mitochondrial membrane potential and increase of intracellular free Ca2+ concentration. In addition, the structure-activity relationships of these derivatives were briefly discussed.

No MeSH data available.


Related in: MedlinePlus