Jia-He Wang

20(s)-ginsenoside Rg3 promotes apoptosis in human ovarian cancer HO-8910 cells through PI3K/Akt and XIAP pathways

Ovarian cancer is a serious tumor which represents a great threat to women’s health. Recently, researchers had found that 20(s)-ginsenoside Rg3 could inhibit growth of several cancer cell lines; however, the mechanism is not fully understood so far. In the present study, we found that 20(s)-ginsenoside Rg3 reduced cell viability and induced apoptosis in a dose- and time-dependent manner in the human ovarian cancer cells HO-8910. The induction of apoptosis was accompanied by downregulation of phosphatidylinositol 3-kinase (PI3K)/Akt family proteins and inhibitor of apoptosis protein (IAP) family proteins. 20(s)-ginsenoside Rg3 treatment resulted in activation of caspase-3 and -9, which may partly explain the anti-cancer activity of 20(s)-ginsenoside Rg3. Taken together, our study for the first time suggests that 20(s)-ginsenoside Rg3 is able to enhance apoptosis of HO-8910 cells, at least in part, through downregulation of PI3K/Akt and IAP family proteins. Moreover, the triggering of caspase-3 and -9 activation mediated apoptotic induction. Our data indicate that 20(s)-ginsenoside Rg3 is an effective apoptosis-inducing natural compound in ovarian cancer cells and may have a role in future therapies for ovarian cancer.

Protective effects of ginsenosides Rg1 and Rb1 on an Alzheimer's disease mouse model: A metabolomics study

Alzheimers disease (AD) is a neurodegenerative disease that affects aging populations, with no effective method for its treatment to date. Elucidating the changes in biofluid small metabolite concentration during AD could improve both diagnosis and treatment. Ginsenosides Rg1 (GRg1) and Rb1 (GRb1), the pharmacologically active ingredients in ginseng, reportedly offer protection against AD symptoms, but the underlying mechanisms are unclear. These were investigated in the present study by examining the metabolite profiles of AD mice. The cognitive function of mice was tested in the Morris water maze and pathological changes to the brain were assessed by immunohistochemistry. Global metabolite profiling by ultra performance liquid chromatography/mass spectrometry and principal component analysis were carried out to identify metabolites that are differentially expressed in AD animals with or without ginsenosides treatment. A total of 10 potential biomarkers were identified that were associated with the metabolism of lecithin, amino acids, and sphingolipids in AD mice. The peak intensities of lysophosphatidylcholine, tryptophan, and dihydrosphingosine were lower, while that of phenylalanine was higher, in AD than in control mice. GRg1 treatment affected all three metabolic pathways, while GRb1 treatment affected lecithin and amino acid but not sphingolipid metabolism. These results provide the first evidence of a link between metabolite imbalance and AD, and reveal a molecular basis for the therapeutic benefits of ginsenosides in AD treatment.

Jolkinolide B from Euphorbia fischeriana Steud induces apoptosis in human leukemic U937 cells through PI3K/Akt and XIAP pathways.

Jolkinolide B, a bioactive diterpene isolated from the roots of Euphorbia fischeriana Steud, is known to induce apoptosis in cancer cells. However, the molecular mechanism of its anti-cancer activity has not been fully elucidated. In the present study, we found that Jolkinolide B reduced cell viability and induced apoptosis in a dose- and timedependent manner in human leukemic U937. The induction of apoptosis was also accompanied by the downregulation of PI3K/Akt and the inhibitor of apoptosis protein (IAP) family proteins. Moreover, we observed that Jolkinolide B treatment resulted in activation of caspase-3 and -9, which may partly explain the anti-cancer activity of Jolkinolide B. Taken together, our study for the first time suggest that Jolkinolide B is able to enhance apoptosis of U937 cells, at least in part, through downregulation of PI3K/Akt and IAP family proteins. Moreover, triggering of caspase-3 and -9 activation mediated apoptotic induction.

Cucurbitacin B inhibits proliferation and induces apoptosis via STAT3 pathway inhibition in A549 lung cancer cells.

Natural products are a great source of cancer chemotherapeutic agents. The present study was conducted to investigate whether cucurbitacin B (CuB), one of the most potent and widely used cucurbitacins, inhibits proliferation and induces apoptosis in the A549 lung cancer cell line. Furthermore, CuB induced apoptosis of A549 cells in a concentration-dependent manner, as determined by fluorescence microscopy, flow cytometry and transmission electron microscopy. The present study also demonstrated that CuB dose-dependently inhibited lung cancer cell proliferation, with cell cycle inhibition and cyclin B1 downregulation. Apoptosis induced by CuB was shown to be associated with cytochrome c release, B-cell lymphoma 2 downregulation and signal transducer and activator of transcription 3 pathway inhibition. CuB may prove to be a useful approach for the chemotherapy of lung cancer.

Rapamycin potentiates cytotoxicity by docetaxel possibly through downregulation of Survivin in lung cancer cells

BackgroundTo elucidate whether rapamycin, the inhibitor of mTOR (mammalian target of rapamycin), can potentiate the cytotoxic effect of docetaxel in lung cancer cells and to probe the mechanism underlying such enhancement.MethodsLung cancer cells were treated with docetaxel and rapamycin. The effect on the proliferation of lung cancer cells was evaluated using the MTT method, and cell apoptosis was measured by flow cytometry. Protein expression and level of phosphorylation were assayed using Western Blot method.ResultsCo-treatment of rapamycin and docetaxel was found to favorably enhance the cytotoxic effect of docetaxel in four lung cancer cell lines. This tumoricidal boost is associated with a reduction in the expression and phosphorylation levels of Survivin and ERK1/2, respectively.ConclusionThe combined application of mTOR inhibitor and docetaxel led to a greater degree of cancer cell killing than that by either compound used alone. Therefore, this combination warrants further investigation in its suitability of serving as a novel therapeutic scheme for treating advanced and recurrent lung cancer patients.

20-(s)-ginsenoside Rg3 induces apoptotic cell death in human leukemic U937 and HL-60 cells through PI3K/Akt pathways.

Leukemia is currently one of the most deadly diseases. Ginseng has been used in Asian countries for the treatment and prevention of various diseases, including leukemia, but the molecular mechanism of its antileukemia activity has not been well defined. The aim of this study was to explore the effect of 20-(s)-ginsenoside Rg3 on apoptosis in human leukemic U937 and HL-60 cells and the underlying mechanism. We found that 20-(s)-ginsenoside Rg3 reduced cell viability and induced apoptosis in U937 and HL-60 cells. The induction of apoptosis was accompanied by the downregulation of PI3K/Akt family proteins. Moreover, we observed that 20-(s)-ginsenoside Rg3 treatment resulted in activation of caspase-3 and caspase-9. Taken together, our findings suggest for the first time that 20-(s)-ginsenoside Rg3 can promote apoptosis in U937 and HL-60 cells, at least partly through the downregulation of PI3K/Akt family proteins. Moreover, the triggering of caspase-3 and caspase-9 activation mediated apoptotic induction. All these findings collectively demonstrate that the natural compound 20-(s)-ginsenoside Rg3 effectively induces apoptosis in human leukemic cells, which suggests that this compound may play a role in future therapies for leukemia.

Involvement of phosphatidylinositol 3-Kinase/Akt signaling pathway in β1 integrin-mediated internalization of Staphylococcus aureus by alveolar epithelial cells

The invasion of Staphylococcus aureus into alveolar epithelial cells is regarded as the key step for S. aureus lung infection. However, the mechanism of internalization of S. aureus by alveolar epithelial cells is not clear, and was the aim of this investigation Human lung adenocarcinomic epithelial cells and A549 cells were used. Human β1 integrin and rat β1 integrin were detected by real-time reverse transcription (RT)-PCR. The expressions of β1 integrin, Akt and p-Akt were detected by Western blot analysis. To further investigate the role of β1 integrin in S. aureus internalization by alveolar epithelial cells, we next performed siRNA-mediated knockdown of β1 integrin expression. In this study, we found that S. aureus invades human alveolar epithelial cells and rat primary alveolar epithelial cells. The β1 integrin ligand competitive inhibitor, GRGDS-peptide, blocked the internalization of S. aureus by A549 cells. Knockdown of β1 integrin also inhibited the internalization of S. aureus. In addition, the PI3K/Akt signaling pathway in alveolar epithelial cells was activated by the infection with S. aureus. Furthermore, Akt phosphorylation was abolished by transient transfection with β1 integrin siRNA in A549 cells challenged with S. aureus. Our results suggest that the phosphatidylinositol 3-kinase/Akt signaling pathway plays an important role in β1 integrin-mediated internalization of S. aureus by alveolar epithelial cells.

Jolkinolide B from Euphorbia fischeriana Steud induces in human leukemic cells apoptosis via JAK2/STAT3 pathways.

Jolkinolide B from the roots of Euphorbia fischeriana Steud exhibits significant antitumor activities against several tumor lines. Previous study has shown that Jolkinolide B could induce apoptosis in human leukemia cells. However, the exact mechanism and signaling pathway involved in Jolkinolide B-induced apoptosis have not been fully elucidated. In the present study, we found that Jolkinolide B reduced cell viability and induced apoptosis in dose- and time-dependent manner in human leukemic HL-60 and THP-1 cells. The induction of apoptosis was accompanied by the downregulation of JAK2/STAT3. Our results also suggest that expression of Bcl-2 and mitochondrial cytochrome c was dosedependently reduced following Jolkinolide B-treated THP-1 and HL-60 cells, whereas Jolkinolide B up-regulated the expression of Bax and cytosolic cytochrome c. Moreover, we observed that Jolkinolide B treatment resulted in activation of caspase-3, -8, and -9. JSI-124, a STAT-3 inhibitor, was able to block the negative effect of Jolkinolide B on cell apoptosis. Taken together, our study for the first time suggests that Jolkinolide B is able to enhance apoptosis of human leukemic HL-60 and THP-1 cells, at least in part, through downregulation of JAK2/STAT3 and bcl-2, and upregulation of Bax and cytosolic cytochrome c. Moreover, the triggering of caspase-3, -8, and -9 activation mediated apoptotic induction.

2-Hydroxy-3-methylanthraquinone from Hedyotis diffusa Willd induces apoptosis in human leukemic U937 cells through modulation of MAPK pathways

The herb of Hedyotis diffusa Willd (H. diffusa Willd), an annual herb distributed in northeastern Asia, has been known as a traditional oriental medicine for the treatment of cancer. Recently, Chinese researchers have discovered that two anthraquinones isolated from a water extract of H. diffusaWilld showed apoptosis-inducing effects against cancer cells. However, the cellular and molecular mechanisms responsible for this phenomenon are poorly understood. The current study determines the role of mitogen-activated protein kinases (MAPK) in human leukemic U937 cells apoptosis induced by 2-hydroxy-3-methylanthraquinone from H. diffusa. Our results showed that 2-hydroxy-3-methylanthraquinone decreased phosphorylation-ERK1/2 (p-ERK1/2), and increased p-p38MAPK, but did not affect expressions of p-JNK1/2 in U937 cells. Moreover, treatment of U937 cells with 2-hydroxy-3-methylanthraquinone resulted in activation of caspase-3. Furthermore, PD98059 (ERK1/2 inhibitor) significantly enhanced 2-hydroxy-3-methylanthraquinone-induced apoptosis in U937 cells, whereas caspase-3 inhibitor or SB203580 (p-p38MAPK inhibitor), decreased apoptosis in U937 cells. Taken together, our study for the first time suggests that 2-hydroxy-3-methylanthraquinone is able to enhance apoptosis of U937 cells, at least in part, through activation of p-p38MAPK and downregulation of p-ERK1/2. Moreover, the triggering of caspase-3 activation mediated apoptotic induction.

Health-related Quality of Life in Women with Breast Cancer: a Literature-based Review of Psychometric Properties of Breast Cancer-specific Measures

BACKGROUND Breast cancer is one of the most common cancers in women in the world. Health-related quality of life (HRQL) at treatment endpoint in cancer clinical trials is widely considered to be increasingly important. The aim of this review was to provide a literature-based assessment of the validity, reliability and responsiveness of breast cancer-specific HRQL instruments in women breast cancer patients. MATERIALS AND METHODS The databases consulted were Medline, PubMed, and Embase. The inclusion criteria required studies to: (1) involve use of HRQL measures; (2) cover women with breast cancer under standard treatment (surgery, radiation therapy, chemotherapy, hormone therapy, and targeted therapy); (3) involve the validity, reliability, or responsiveness of HRQL; (4) deal with validation of breast cancer-specific HRQL instruments. RESULTS A total of 16 studies were identified through the literature search that met the 4 inclusion criteria. Some seven instruments were assessed among these 16 studies: EORTC QLQ-BR23, FACT-B, FACT-ES, HFRDIS, LSQ- 32, QLICP-BR, and SLDS-BC. EORTC QLQ-BR23, FACT-B, LSQ-32, QLICP-BR, and SLDS-BC are more general breast cancer-specific HRQL instruments. FACT-EB is the endocrine subscale combined with FACT-B in order to measure the side effects and putative benefits of hormonal treatment administered in breast cancer patients. HFRDIS is the HRQL measure focusing on hot flash concerns. CONCLUSIONS This paper provides an overall understanding on the currently available breast cancer-specific HRQL instruments in women breast cancer patients.