Lijing Zhang

Caesalpins A-H, bioactive cassane-type diterpenes from the seeds of Caesalpinia minax.

Eight new cassane-type diterpenes, caesalpins A-H (1-8), were isolated from the ethyl acetate extract of Caesalpinia minax. Compound 1 displayed significant antiproliferative activity against HepG-2 (IC50 4.7 μM) and MCF-7 (IC50 2.1 μM) cells, and compounds 2 and 4 exhibited selective cytotoxic activities against MCF-7 (IC50 7.9 μM) and AGS (IC50 6.5 μM) cells.

Sesquiterpene coumarins from seeds of Ferula sinkiangensis

A new sesquiterpene coumarin with a novel sesquiterpene carbon framework, Sinkiangenorin D, and ten known sesquiterpene coumarins were isolated from the seeds of Ferula sinkiangensis. The structures of these compounds, including the relative stereochemistry, were elucidated on the basis of spectroscopic data. All of the isolated compounds were tested against the AGS, HeLa, and K562 human cancer cell lines and showed cytotoxic activities with 50% inhibitory concentration values between 12.7 and 226.6 μM.

Antiinflammatory and Analgesic Activities of Ethanol Extract and Isolated Compounds from Millettia pulchra

The plant Millettia pulchra was commonly used in folk medicine for the management of inflammation. However, there was no scientific rationale for these effects and the mechanism of action remained incompletely understood. The present study was designed to investigate the antiinflammatory and analgesic activities of an ethanol extract of the stem of M. pulchra (EMP) in vivo, and to explore the antiinflammatory activity of compounds isolated from EMP in vitro. We found that EMP reduced xylene-induced ear edema and relieved both acetic acid-induced pain and pain in the hot plate test. Additionally, a significant decrease in nitric oxide (NO) production was observed in cells treated with the isolated compounds. Lanceolatin B, which showed the greatest inhibition of NO synthesis among the compounds tested, also reduced levels of interleukin-1 beta (IL-1β), IL-6, tumor necrosis factor-alpha (TNF-α), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), nuclear factor-kappa B (NF-κB), and phosphorylation inhibitory kappa B alpha (p-IκBα) in a dose-dependent manner. These findings provide convincing evidence that EMP and the individual isolated compounds possess significant antiinflammatory and analgesic activities.

Two new cardenolides from the roots of Streptocaulon griffithii

Two new cardenolides, 3β,5β,14β-trihydroxyl-card-16,20(22)-dienolide (1) and 3-O-β-d-glucopyranosyl-5β,14β-dihydroxyl-card-16,20(22)-dienolide (2), together with seven known compounds identified as digitogenin (3), 16-O-acetylgitoxigenin (4), periplogenin (5), 16-O-acetylperiplogenin (6), periplogenin digitoxoside (7), periplogenin-3-O-β-d-glucopyranoside (8) and periplogenin-3-O-β-d-glucopyranosyl-(1 → 4)-O-β-d-digitoxopyranoside (9) were isolated from the roots of Streptocaulon griffithii. Their structures were elucidated on the basis of spectroscopic data.

Quantitative analysis of differential protein expression in cervical carcinoma cells after zeylenone treatment by stable isotope labeling with amino acids in cell culture

Cervical carcinoma is a malignant tumor that poses a serious threat to womens health and survival. Approximately 10-25% of cervical cancers are adenocarcinomas (ACs). AC has high rates of recurrence and mortality, while there is no effective treatment for now. Zeylenone (Zey), which is isolated from an ethanol extract of the leaves of Uvaria grandiflora Roxb. of the family Annonaceae, has shown potent inhibitory activity against various tumor cells, including cervical carcinoma cells. To gain insight into the molecular mechanism underlying the effect of Zey on AC, we quantified protein expression changes in AC cells treated with Zey. We used stable isotope labeling with amino acids in cell culture (SILAC) in combination with high-performance liquid chromatography-electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) and bioinformatics analysis to compare protein expression profiles in HeLa cells before and after Zey treatment. Of 1805 differentially expressed proteins identified, 229 were screened as key protein molecules and classified into nine categories. Profiling of differentially-expressed proteins contributed to our understanding of the molecular mechanism by which Zey induces HeLa cell apoptosis. Using this method, candidate targets can be identified for developing new drugs against cervical carcinoma.

Umbelliprenin and lariciresinol isolated from a long-term-used herb medicine Ferula sinkiangensis induce apoptosis and G0/G1 arresting in gastric cancer cells

Effective chemicals isolated from folk medicine are commonly used in the treatment of cancer in Asian countries like China and India. Ferula sinkiangensis K. M. Shen is a traditional herb medicine used for treating stomach disorders in Xinjiang District of China for thousands of years. Here, we showed that the growth inhibition effects of seven compounds first isolated from the seeds of this herb in human gastric cancer cells and human normal gastric epithelium cells. Furthermore, we characterized the mechanism of the antiproliferation effects on gastric cancer cells of the two most specific and effective compounds: umbelliprenin (UM) and lariciresinol (LA). Annexin V/PI staining demonstrated that UM and LA induce apoptosis in gastric cancer AGS cells. Loss of mitochondrial membrane potential, upregulation of proapoptotic protein BAX, and activation of caspase 3 and PARP suggested that UM and LA caused the activation of the mitochondrial apoptosis pathway. Cell cycle analysis showed that UM and LA arrest cell cycle at G0/G1 phase. Western blot results showed that the expression of P53, P27, P16 and Rb proteins increased, while the expression of cyclin D, cyclin E, Cdk4 and Cdk2 decreased in cancer cells. Overall, these data provided evidence that UM and LA have the potential to be used in cancer therapy.

Capilliposide C derived from Lysimachia capillipes Hemsl inhibits growth of human prostate cancer PC3 cells by targeting caspase and MAPK pathways

Prostate cancer, a common malignant tumor of the genitourinary system among elderly males, is difficult to cure. Capilliposide C (CPS-C) is a novel oleanane triterpenoid saponin derived from Lysimachia capillipes Hemsl. Although CPS-C had been investigated in gastric cancer BGC-823 cells, prostate cancer PC3 cells, and ovarian cancer SK-OV-3 cells in nude mice in a dose-dependent manner without overt toxicity, its mechanism in the cancer cells has not been further studied. In the current study, PC3-cell-line-based in vitro models were used to explore the anti-cancer effect and mechanism of CPS-C. The results of cell viability assays showed that CPS-C exhibited dose- and time-dependent cytotoxicity against the prostate cancer cell lines PC3 and DU145. Observations using optical and electron microscope suggested the cytotoxicity of CPS-C. CPS-C-induced apoptosis was confirmed by the activation of caspases, down-regulation of Bcl-2, JNK, and P38α/β, and up-regulation of Bax, p-JNK, and p-P38. Results showed that CPS-C exhibits high toxicity toward two prostate cancer cells in vitro. Therefore, CPS-C may have great potential in the prevention and treatment of human prostate cancers.

A new phenylethanoid glycoside from Incarvillea compacta

Abstract A new phenylethanoid glycoside, 3′′′-O-methylcampneoside I (1), was isolated from the 90% ethanolic extract of the roots of Incarvillea compacta, together with three known compounds, campneoside I (2), ilicifolioside A (3), and campneoside II (4). Their structures were determined spectroscopically and compared with previously reported spectral data. Compound 1 existed as epimers and displayed better 1,1-diphenyl-2-picrylhydrazyl (DPPH)-free radical scavenging activity using di-tert-butyl-4-methylphenol (BHT) as the positive control. In addition, pretreatment of human HepG2 cells with compound 1 significantly increased the viability on CCl4-induced cell death.

Trichloromethane fraction of Incarvillea compacta induces lytic cytotoxicity and apoptosis in Epstein-Barr virus-positive gastric cancer AGS cells

AbstractsBackgroundIncarvillea compacta Maxim. has been used to treat stomach disease in Tibet for many years. The objectives of this study were to explore the anti-cancer ability of trichloromethane fraction of I. compacta Maxim. roots (IC-TCL, R2) in EBV positive AGS cancer cells and its effects on cell cycle arrest, apoptosis and lytic induction.MethodsMTT and trypan blue assays were to detect the inhibitory effects of different fraction in different cell lines. Hoechst 33342 staining, Annexin V-PE/7-AAD staining and DIOC6 staining were used to detect the apoptosis induction effects of R2. Western blot experiments were used to detect the expression of apoptosis related proteins BAX and Bcl-2, EBV lytic related proteins BZLF1 and BMRF1, cell cycle regulation related proteins Cyclin D1 and RB after R2 treatment. Cell cycle arrest was analyzed by flow cytometry.ResultsMTT and trypan blue assays revealed that R2 could significantly reduce cell viability in a dose-dependent manner in EBV positive AGS cells compared with non-EBV infected AGS and other cancer cell lines, whereas n-BuOH and H2O fractions showed non-inhibitory effects in tested cancer cells. R2 could decrease mitochondrial membrane potential and the expression of Bcl-2, while increase the expression of BAX. R2 could also induce EBV lytic replication by activating mRNA levels of BZLF1, BRLF1 and BMRF1. Protein expressions of BZLF1 and BMRF1 were also increased after R2 treatment. Cell cycle analysis showed that R2 treatment could induce G0/G1 phase arrest. The expression of Cyclin D1 decreased, while Rb increased.ConclusionsThese results demonstrated that R2 could inhibit the proliferation of AGS-EBV cancer cells by inducing EBV lytic replication, apoptosis and G0/G1 arrest, through the regulation of related proteins. Therefore, R2 could be used as a potential treatment in AGS-EBV cells.

Photodynamic diagnosis of gastric cancer using HPPH-CD

Gastric cancer is associated with a poor prognosis and is the fourth most common carcinoma and the second leading cause of cancer-related mortality worldwide due to its late-stage diagnosis and recurrence. New strategies are urgently needed to improve this condition. 2-[1′-Hexyloxyethyl]-2-devinyl pyropheophorbide-(HPPH)-cyanine dye (CD) mediated photodynamic diagnosis (PDD) has attracted great attention as a relatively new modality for tumor diagnosis. However, the efficacy of HPPH-CD-PDD on gastric cancer is poorly understood. The present study evaluates the effectiveness of PDD on gastric cancer diagnosis using HPPH-CD. We first evaluated the imaging potential of HPPH-CD on ICR mice bearing S180 subcutaneous tumors to make a preliminary definition of the ideal conditions for diagnosis. Subsequently, animal models with gastric cancer were established by giving 3,4-benzopyrene (B(a)P) to KM mice and 1-methyl-3-nitro-1-nitrosoguanidine (MNNG) to Wistar rats. The fluorescence signals of the stomach were then detected after HPPH-CD delivery, followed by imaging under a standard bright field. Furthermore, the tumors were collected, fixed and processed for histologic review. We found that subcutaneous S180 tumors and orthotopic primary gastric tumors could be easily visualized with fluorescence imaging after the delivery of HPPH-CD, and all malignant lesions with strong fluorescence were histologically confirmed. These results revealed the potential of HPPH-CD as a novel photosensitizer for the enhanced visualization of tumors in gastric cancer.