ORCID Profile
0000-0003-0317-9029
Current Organisation
Yantai University
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Publisher: Elsevier BV
Date: 06-2012
DOI: 10.1016/J.LUNGCAN.2011.12.013
Abstract: Riccardin D is a macrocyclic bisbibenzyl compound extracted from liverwort plant Dumortiera hirsuta. Our previous study showed that riccardin D induced apoptosis of human leukemia cells by targeting DNA topoisomerase II (topo II). Riccardin D has been considered as a novel DNA topo II inhibitor and potential chemotherapeutic agent for treatment of cancers. In this study, we evaluated the inhibitory effects of riccardin D on growth of human non-small cell lung cancer (NSCLC) both in vitro and in vivo. Riccardin D effectively inhibited the proliferation of NSCLC cells as estimated by the MTT assay. Further examination showed that the ability of invasion and migration of NSCLC cells was suppressed on exposure to riccardin D as estimated by the assays of scratch and transwell chamber. The anticancer activity of riccardin D was verified in mice bearing human NSCLC H460 xenografts. Riccardin D injection produced a 44.5% inhibition of cancer growth without apparent signs of toxicity to animals. Further, riccardin D induced apoptosis of NSCLC cells as evidenced by the increases of cells with externalization of phosphatidylserine and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL)-positive in H460 xenografts. The analysis of apoptotic proteins showed that riccardin D activated the caspases cascade signaling pathway as demonstrated by the increases of cleaved caspase-3 and cleaved PARP in NSCLC cells in vitro and in H460 xenografts in mice. The pBR322 DNA relaxation assay indicated that riccardin D inhibited the activity of DNA topo II in H460 and A549 cells, suggesting the mechanism of riccardin D in induction of NSCLC apoptosis. In addition, we studied the activity and expression of matrix metalloproteinases (MMPs) in NSCLC cells. The activities of MMP-2 and MMP-9 in supernatants of NSCLC cells were suppressed on exposure to riccardin D as estimated by gelatin zymography assay. The inhibitory effects of riccardin D on expressions of MMP-2 and MMP-9 were verified in H460 xenografts in mice and the decreases of vascular endothelial growth factor (VEGF) and Erk1/2 might associate with the inhibition of MMPs and NSCLC growth. Together, our results suggest that riccardin D has a high inhibitory effect on human NSCLC growth through induction of apoptosis.
Publisher: Springer Science and Business Media LLC
Date: 06-10-2010
DOI: 10.1007/S10637-010-9554-8
Abstract: We studied the effect of riccardin D, a macrocyclic bisbibenzyl, which was isolated from the Chinese liverwort plant, on human leukemia cells and the underlying molecular mechanism. Riccardin D had a significant antiproliferative effect on human leukemia cell lines HL-60, K562 and its multidrug resistant (MDR) counterpart K562/A02 cells, but showed no effect on the topoisomerase-II-deficient HL-60/MX2 cells, as measured by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. The pBR322 DNA relaxation assay revealed that riccardin D selectively inhibited the activity of topoisomerase II (topo II). The suppression of topo II activity by riccardin D was stronger than that of etoposide, a known topo II inhibitor. After treatment with riccardin D, nuclear extracts of leukemia K562 and K562/A02 cells left the majority of pBR322 DNA in a supercoiled form. Further examination showed that riccardin D effectively induced HL-60, K562 and K562/A02 apoptosis as evidenced by externalization of phosphatidylserine and formation of DNA ladder fragments. The activation of cytochrome c, caspase-9, caspase-3 and cleaved poly ADP-ribose polymerase (PARP) was also enhanced, as estimated by Western blot analysis. By contrast, riccardin D was unable to induce apoptosis in the topoisomerase-II-deficient HL-60/MX2 cells, indicating that the induction of apoptosis by riccardin D was due to the inhibition of topo II activity. In addition, riccardin D was able to significantly decrease P-glycoprotein (P-gp) expression in K562/A02 cells. Taken together, our data demonstrate that riccardin D is a novel DNA topo II inhibitor which can induce apoptosis of human leukemia cells and that it has therapeutic potential for both regular and MDR strains of leukemia cells.
Publisher: Elsevier BV
Date: 04-2013
Publisher: Elsevier BV
Date: 09-2011
DOI: 10.1016/J.EJPHAR.2011.06.013
Abstract: Riccardin D is a novel macrocyclic bisbibenzyl compound extracted from Chinese liverwort plant Dumortiera hirsuta. Our previous studies showed that riccardin D is a DNA topo II inhibitor and has therapeutic potential for treatment of cancers. In this combined in vitro and in vivo study, we examined the inhibitory effects of riccardin D on tumor angiogenesis and the subsequent effect of anticancer activity was evaluated. Incubation with riccardin D weakly inhibited the proliferation of human umbilical vascular endothelial cells (HUVEC) as estimated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The scratch wound experiment showed that riccardin D effectively decreased the motility and migration of HUVEC cells. Riccardin D inhibited the formation of capillary tube as demonstrated by decrease of branch points formed by HUVEC cells on 3-D Matrigel. We examined the levels of angiogenic factors including vascular endothelial growth factor (VEGF), VEGF receptor 2, epidermal growth factor receptor (EGF receptor), and matrix metalloproteinase (MMPs) in HUVEC cells. The expressions of VEGF, phospho-VEGF receptor 2, EGF receptor and MMP-2 were significantly reduced by riccardin D as estimated by Western blot assay and real-time quantitative PCR analysis. The decrease of VEGF was also detected in riccardin D-treated human lung cancer H460 cells. The anticancer activity of riccardin D was then evaluated in a mouse model in which riccardin D delayed the growth of H460 xenografts without obvious toxicity to animals after three weeks injection. To evaluate the role of antiangiogenesis of riccardin D in mice, CD34 immunohistochemical staining was employed to analyze the mean vascular density in H460 xenograft tissues. The number of blood vessels was significantly decreased after riccardin D treatment. These results suggest that riccardin D display the inhibitory effect on growth of human lung carcinoma cells and that the inhibition of angiogenesis may involve in anticancer activity of riccardin D.
Publisher: Spandidos Publications
Date: 16-02-2018
Publisher: Wiley
Date: 26-11-2012
DOI: 10.1002/IJC.27929
Abstract: Acetyl-11-keto-beta-boswellic acid (AKBA) is a derivative of boswellic acid, which is an active component of the gum resin of Boswellia serrata. AKBA has been used as an adjuvant medication for treatment of inflammatory diseases. In this study, we aimed to evaluate the efficacy of AKBA as a chemopreventive agent against intestinal adenomatous polyposis in the adenomatous polyposis coli multiple intestinal neoplasia (APC(Min/+) ) mouse model. APC(Min/+) mice were administered AKBA by p.o. gavage for 8 consecutive weeks. The mice were sacrificed and the number, size and histopathology of intestinal polyps were examined by light microscopy. AKBA decreased polyp numbers by 48.9% in the small intestine and 60.4% in the colon. An even greater AKBA effect was observed in preventing the malignant progression of these polyps. The number of large (>3 cm) colonic polyposis was reduced by 77.8%. Histopathologic analysis demonstrated a significant reduction in the number of dysplastic cells and in the degree of dysplasia in each polyp after AKBA treatment. There was no evidence of high grade dysplasia or intramucosal carcinoma in any of the polyps examined within the treated group. More interestingly, interdigitated normal appearing intestinal villi were observed in the polyps of the treated group. During the course of the study, AKBA was well tolerated by the mice with no obvious signs of toxicity. Results from immunohistochemical staining, Western blotting and enzyme-linked immunosorbent assay indicated that the chemopreventive effect of AKBA was attributed to a collection of activities including antiproliferation, apoptosis induction, antiangiogenesis and anti-inflammation. AKBA was found to exert its chemopreventive action through the inhibition of the Wnt/β-catenin and NF-κB/cyclooxygenase-2 signaling pathways. Our findings suggest that AKBA could be a promising regimen in chemoprevention against intestinal tumorigenesis.
Publisher: Public Library of Science (PLoS)
Date: 14-03-2012
Publisher: Springer Science and Business Media LLC
Date: 11-08-2020
DOI: 10.1038/S41388-020-01415-8
Abstract: Breast cancer is making up one-quarter of all new female cancer cases diagnosed worldwide. Breast cancer surgeries, radiation therapies, cytotoxic chemotherapies and targeted therapies have made significant progress and play a dominant role in breast cancer patient management. However, many challenges remain, including resistance to systemic therapies, tumour recurrence and metastasis. The cyclic neuropeptide oxytocin (OT) elicits a plethora of biological responses via the oxytocin receptor (OTR) in both the central and peripheral nervous system, including social bonding, stress, maternal behaviour, sexual activity, uterus contraction, milk ejection and cancer. As a typical member of the G protein-coupled receptor family, OTR represents also an intriguing target for cancer therapy. There is emerging evidence that OTR plays a role in breast cancer development and progression, and several breast cancer cell lines express OTR. However, despite supporting evidence that OT lowers breast cancer risks, its mechanistic role in breast cancer development and the related signalling pathways are not fully understood. Here, we review the current knowledge of the OT/OTR signalling system in healthy breast tissue as well as in breast cancer, and discuss OTR as a potential therapeutic target for breast cancer management.
Publisher: MDPI AG
Date: 05-07-2022
DOI: 10.3390/BIOMEDICINES10071595
Abstract: Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype with limited treatment options and high mortality. The oxytocin receptor (OTR) is a class-A G protein-coupled receptor that has been linked to breast cancer, but its role in tumorigenesis and disease progression remains underexplored. OTR expression is highest in tumour-adjacent breast tissue, followed by normal and tumour tissue, indicating a potential role in the tumour microenvironment. OTR levels were higher in migrated MDA-MB-231 cells than in the control parental cells cultured in normal medium OTR overexpression/knock-down and metastasis biomarker experiments revealed that high OTR expression enhanced metastasis capabilities. These findings align well with data from a murine breast cancer metastasis model, where metastasised tumours had higher OTR expression than the corresponding primary tumours, and high OTR expression also correlates to reduced survival in TNBC patients. OTR agonists/antagonists did not affect MDA-MB-231 cell migration, and pharmacological analysis revealed that the OT/OTR signalling was compromised. High OTR expression enhanced cell migration in an OTR ligand-independent manner, with the underlying mechanism linked to the EGF-mediated ERK1/2-RSK-rpS6 pathway. Taken together, high OTR expression seems to be involved in TNBC metastasis via increasing cell sensitivity to EGF. These results support a potential prognostic biomarker role of OTR and provide new mechanistic insights and opportunities for targeted treatment options for TNBC.
Publisher: Elsevier BV
Date: 06-2012
DOI: 10.1016/J.CANLET.2012.01.012
Abstract: All-trans retinoic acid (ATRA) is a promising therapeutic agent, but exhibits low efficacy against human cancers. We investigated the effect of sphingosine-1-phosphate (S1P) on ATRA activity in human colon cancer HT-29 cells. S1P antagonized ATRA activity on HT-29 cell proliferation and retinoic acid receptor beta (RARβ) expression. S1P treatment or transient co-transfection with SphK2 expression vector antagonized ATRA-induced RARβ promoter activity. Proteasome inhibition prevented S1P-induced modulation of ATRA activity. Overall, S1P antagonized ATRA's inhibitory effects by down-regulating RARβ expression, likely via the proteasome-dependent pathway. Decreasing S1P production or inhibiting SphK2 activity could enhance the efficacy of retinoids in cancer treatments.
Publisher: University of Queensland Library
Date: 2021
DOI: 10.14264/964E5B2
Publisher: Elsevier BV
Date: 08-2012
DOI: 10.1016/J.TAAP.2012.05.006
Abstract: SL-01, an oral gemcitabine derivative, was synthesized by introducing the moiety of 3-(dodecyloxycarbonyl)pyrazine-2-carbonyl at the N4-position on the cytidine ring of gemcitabine. Our goal in this study was to evaluate the efficacy of SL-01 on the growth of human cancers with gemcitabine as control. Experiments were performed on human non-small cell lung cancer NCI-H460 and colon cancer HCT-116 both in vitro and in vivo. In vitro assays, SL-01 significantly inhibited the growth of cancer cells as determined by the 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) assay. Further studies indicated that SL-01 induced the cancer cells to apoptosis showing chromatin condensation and externalization of phosphatidylserine. In in vivo studies, we evaluated the efficacy of SL-01 in nude mice bearing human cancer xenografts. SL-01 effectively delayed the growth of NCI-H460 and HCT-116 without significant loss of body weight. Molecular analysis indicated that the high efficacy of SL-01 was associated with its ability to induce apoptosis as evidenced by increase of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining cells, activation of caspase-9, caspase-3 and cleaved poly ADP-ribose polymerase (PARP) in tumor tissues. SL-01 also increased Bax/Bcl-2 ratio in cancer cells. These biological activities of SL-01 were more potential than that of gemcitabine. Based on these in vitro and in vivo results, SL-01 is proposed as a potent oral anticancer agent that may supplant the use of gemcitabine in the clinic.
Publisher: Springer Science and Business Media LLC
Date: 05-03-2011
Location: Australia
No related grants have been discovered for Huiping Liu.