scholarly journals Andrographolide Induces Apoptosis of C6 Glioma Cells via the ERK-p53-Caspase 7-PARP Pathway

2014 ◽  
Vol 2014 ◽  
pp. 1-15 ◽  
Author(s):  
Shih-Hung Yang ◽  
Seu-Mei Wang ◽  
Jhih-Pu Syu ◽  
Ying Chen ◽  
Sheng-De Wang ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Signaling Pathway ◽  
C6 Glioma Cells ◽  
Nuclear Staining ◽  
Anticancer Effects ◽  
Caspase 7 ◽  
The Central Nervous System ◽  
Induced Apoptosis

Background.Glioma is the most malignant tumor of the central nervous system. Efforts on the development of new chemotherapy are mandatory. Andrographolide (AND), a diterpenoid lactone isolated from theAndrographis paniculata, has been shown to have antitumor activities in several types of cancer cells. Whether AND can exert its antitumor activity in glioblastoma cells remains unknown. This study examined the anticancer effects of AND, bothin vitroandin vivo.Methods.Cell apoptosis was assayed by flow cytometry and nuclear staining. The signaling pathway for AND was determined by western blotting. The effects of AND on tumor growth was evaluated in a mouse model.Results and Conclusion. In vitro, with application of specific inhibitors and siRNA, AND-induced apoptosis was proven through ROS-ERK-P53-caspase 7-PARP signaling pathway.In vivo, AND significantly retarded tumor growth and caused regression of well-formed tumorsin vivo. Furthermore, AND did not induce apoptosis or activate ERK and p53 in primary cultured astrocyte cells, and it may serve as a potential therapeutic candidate for the treatment of glioma.

scholarly journals Bortezomib potentiates antitumor activity of Mitoxantrone through dampening Wnt/β-catenin signaling pathway in prostate cancel cells

2021 ◽  
Author(s):  
Ying Zhang ◽  
Qiuzi Liu ◽  
Wei Wei ◽  
Guoan Zhang ◽  
Siyuan Yan ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Antitumor Activity ◽  
Signaling Pathway ◽  
Target Genes ◽  
Proliferation Assay ◽  
Prostate Cancer Cells ◽  
Anticancer Effects ◽  
Induced Apoptosis

Abstract Background Bortezomib (BZM), alone or in combination with other chemotherapies, has displayed strong anticancer effects in several cancers. The efficacy of the combination of BZM and mitoxantrone (MTX) in treating prostate cancer remains unknown.Methods Anticancer effects of combination of BZM and MTX were determined by apoptosis and proliferation assay in vivo and in vitro. Expression of β-catenin and its target genes were characterized by western blot and Real-time PCR.Results BZM significantly enhanced MTX-induced antiproliferation in vivo and in vitro. Mice administered a combination of BZM and MTX displayed attenuated tumor growth and prolonged survival. BZM significantly attenuated MTX-induced apoptosis. Moreover, the combination of BZM and MTX contributed to inhibition of the Wnt/β-catenin signaling pathway compared to monotherapy.Conclusions This study demonstrates that BZM enhances MTX-induced anti-tumor effects by inhibiting the Wnt/β-catenin signaling pathway in prostate cancer cells.

scholarly journals Bortezomib potentiates antitumor activity of mitoxantrone through dampening Wnt/β-catenin signal pathway in prostate cancer cells

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ying Zhang ◽  
Qiuzi Liu ◽  
Wei Wei ◽  
Guoan Zhang ◽  
Siyuan Yan ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Target Genes ◽  
Signal Pathway ◽  
Prostate Cancer Cells ◽  
Anticancer Effects ◽  
Induced Apoptosis

Abstract Background Bortezomib (BZM), alone or in combination with other chemotherapies, has displayed strong anticancer effects in several cancers. The efficacy of the combination of BZM and mitoxantrone (MTX) in treating prostate cancer remains unknown. Methods Anticancer effects of combination of BZM and MTX were determined by apoptosis and proliferation assay in vivo and in vitro. Expression of β-Catenin and its target genes were characterized by western blot and Real-time PCR. Results BZM significantly enhanced MTX-induced antiproliferation in vivo and in vitro. Mice administered a combination of BZM and MTX displayed attenuated tumor growth and prolonged survival. BZM significantly attenuated MTX-induced apoptosis. Moreover, the combination of BZM and MTX contributed to inhibition of the Wnt/β-Catenin signaling pathway compared to monotherapy. Conclusions This study demonstrates that BZM enhances MTX-induced anti-tumor effects by inhibiting the Wnt/β-Catenin signaling pathway in prostate cancer cells.

scholarly journals The PI3K Inhibitor XH30 Enhances Response to Temozolomide in Drug-Resistant Glioblastoma via the Noncanonical Hedgehog Signaling Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Ming Ji ◽  
Zhihui Zhang ◽  
Songwen Lin ◽  
Chunyang Wang ◽  
Jing Jin ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Hedgehog Signaling ◽  
Kinase Inhibitor ◽  
Therapeutic Option ◽  
Hedgehog Signaling Pathway ◽  
Orthotopic Mouse Model ◽  
Cycle Arrest ◽  
The Central Nervous System

Glioblastoma multiforme (GBM) is the most common malignant tumor of the central nervous system. Temozolomide (TMZ)–based adjuvant treatment has improved overall survival, but clinical outcomes remain poor; TMZ resistance is one of the main reasons for this. Here, we report a new phosphatidylinositide 3-kinase inhibitor, XH30; this study aimed to assess the antitumor activity of this compound against TMZ-resistant GBM. XH30 inhibited cell proliferation in TMZ-resistant GBM cells (U251/TMZ and T98G) and induced cell cycle arrest in the G1 phase. In an orthotopic mouse model, XH30 suppressed TMZ-resistant tumor growth. XH30 was also shown to enhance TMZ cytotoxicity both in vitro and in vivo. Mechanistically, the synergistic effect of XH30 may be attributed to its repression of the key transcription factor GLI1 via the noncanonical hedgehog signaling pathway. XH30 reversed sonic hedgehog–triggered GLI1 activation and decreased GLI1 activation by insulin-like growth factor 1 via the noncanonical hedgehog signaling pathway. These results indicate that XH30 may represent a novel therapeutic option for TMZ-resistant GBM.

scholarly journals Synergistic antitumor effect of 5-fluorouracil with the novel LSD1 inhibitor ZY0511 in colorectal cancer

2020 ◽  
Vol 12 ◽  
pp. 175883592093742
Author(s):  
Wen Peng ◽  
Huaqing Zhang ◽  
Shisheng Tan ◽  
Yan Li ◽  
Yang Zhou ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Antitumor Effect ◽  
Underlying Mechanism ◽  
Synergistic Antitumor Effect ◽  
Anticancer Effects ◽  
Potential Marker ◽  
And Migration ◽  
Induced Apoptosis

Background: Lysine-specific histone demethylase 1 (LSD1) is a potential target of cancer therapy. In the present study, we aimed to investigate the combined antitumor activity of a novel LSD1 inhibitor (ZY0511) with 5-fluorouracil (5-FU) and elucidate the underlying mechanism in colorectal cancer (CRC). Methods: We evaluated LSD1 expression in CRC tissues from patients who received 5-FU treatment. The synergistic antitumor effect of 5-FU with ZY0511 against human CRC cells was detected both in vitro and in vivo. The underlying mechanism was explored based on mRNA sequencing (mRNA-seq) technology. Results: Overexpression of LSD1 was observed in human CRC tissues, and correlated with CRC development and 5-FU resistance. ZY0511, a novel LSD1 inhibitor, effectively inhibited CRC cells proliferation, both in vitro and in vivo. Notably, the combination of ZY0511 and 5-FU synergistically reduced CRC cells viability and migration in vitro. It also suppressed Wnt/β-catenin signaling and DNA synthesis pathways, which finally induced apoptosis of CRC cells. In addition, the combination of ZY0511 with 5-FU significantly reduced CRC xenograft tumor growth, along with lung and liver metastases in vivo. Conclusions: Our findings identify LSD1 as a potential marker for 5-FU resistance in CRC. ZY0511 is a promising candidate for CRC therapy as it potentiates 5-FU anticancer effects, thereby providing a new combinatorial strategy for treating CRC.

scholarly journals The endocannabinoid anandamide inhibits cholangiocarcinoma growth via activation of the noncanonical Wnt signaling pathway

2008 ◽  
Vol 295 (6) ◽  
pp. G1150-G1158 ◽  
Author(s):  
Sharon DeMorrow ◽  
Heather Francis ◽  
Eugenio Gaudio ◽  
Julie Venter ◽  
Antonio Franchitto ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Tumor Growth ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Calcium Release ◽  
Wnt Signaling Pathway ◽  
Xenograft Model ◽  
Orphan Receptor

Cholangiocarcinomas are cancers that have poor prognosis and limited treatment options. The noncanonical Wnt pathway is mediated predominantly by Wnt 5a, which activates a Ca2+-dependent pathway involving protein kinase C, or a Ca2+-independent pathway involving the orphan receptor Ror2 and subsequent activation of Jun NH2-terminal kinase (JNK). This pathway is associated with growth-suppressing effects in numerous cell types. We have shown that anandamide decreases cholangiocarcinoma growth in vitro. Therefore, we determined the effects of anandamide on cholangiocarcinoma tumor growth in vivo using a xenograft model and evaluated the effects of anandamide on the noncanonical Wnt signaling pathways. Chronic administration of anandamide decreased tumor growth and was associated with increased Wnt 5a expression in vitro and in vivo. Treatment of cholangiocarcinoma cells with recombinant Wnt 5a decreased cell proliferation in vitro. Neither anandamide nor Wnt 5a affected intracellular calcium release, but both increased the JNK phosphorylation. Stable knockdown of Wnt 5a or Ror2 expression in cholangiocarcinoma cells abolished the effects of anandamide on cell proliferation and JNK activation. Modulation of the endocannabinoid system may be important in cholangiocarcinoma treatment. The antiproliferative actions of the noncanonical Wnt signaling pathway warrants further investigation to dissect the mechanism by which this may occur.

scholarly journals Neutrophil Elastase Induces Chondrocyte Apoptosis and Facilitates the Occurrence of Osteoarthritis via Caspase Signaling Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Ganyu Wang ◽  
Weiqiang Jing ◽  
Yuxuan Bi ◽  
Yue Li ◽  
Liang Ma ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Neutrophil Elastase ◽  
Elderly Population ◽  
The Elderly ◽  
Chondrocyte Apoptosis ◽  
Intracellular Ros ◽  
Induced Apoptosis

Osteoarthritis (OA) is the most common and prevalent chronic joint disorders in the elderly population across the globe, resulting in severe disability and impairment of quality of life. Existing treatment can only alleviate the symptoms and delay the progression of OA. Therefore, novel and effective therapeutics strategies for OA need to be developed. Our present study first found that neutrophil elastase (NE) was significantly increased in OA patients’ synovial fluid. Next, we examined the effect of neutrophil elastase (NE) on chondrocytes in vitro and in vivo. The results showed that NE suppressed cell proliferation, induced apoptosis and prevented cell migration in chondrocytes in vitro, accompanied by the elevation of intracellular ROS and calcium level. Moreover, NE enhanced the cleaved caspase-3 levels and disrupted the mitochondrial transmembrane potential balance. Meanwhile, chondrocytes apoptosis induced by NE can be alleviated by caspase inhibitor, zVAD-FMK and antioxidants, GSH. Besides, treatment of sivelestat, the inhibitor of NE, significantly reduced the pathological processes in OA model rats in vivo. The results of our study suggested that NE is an important factor in OA, which induces chondrocyte apoptosis and facilitates the occurrence of OA via caspase signaling pathway, and targeting the crucial signal centering around NE may be the potential therapies for OA.

scholarly journals MiR-1246 regulates the PI3K/AKT signaling pathway by targeting PIK3AP1 and inhibits thyroid cancer cell proliferation and tumor growth

2021 ◽  
Author(s):  
Jingyan Li ◽  
Zhanlei Zhang ◽  
Jieting Hu ◽  
Xiaoting Wan ◽  
Wei Huang ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Tumor Growth ◽  
Signaling Pathway ◽  
Gene Expression Omnibus ◽  
Akt Signaling ◽  
Akt Phosphorylation ◽  
Apoptotic Death ◽  
Phosphoinositide 3 Kinase

AbstractOne of the most prevalent forms of endocrine malignancies is thyroid cancer. Herein, we explored the mechanisms whereby miR-1246 is involved in thyroid cancer. Phosphoinositide 3-kinase adapter protein 1 (PIK3AP1) was identified as a potential miR-1246 target, with the online Gene Expression Omnibus (GEO) database. The binding between miR-1246 and PIK3AP1 and the dynamic role of these two molecules in downstream PI3K/AKT signaling were evaluated. Analysis of GEO data demonstrated significant miR-1246 downregulation in thyroid cancer, and we confirmed that overexpression of miR-1246 can inhibit migratory, invasive, and proliferative activity in vitro and tumor growth in vivo. Subsequent studies indicated that miR-1246 overexpression decreased the protein level of PIK3AP1 and the phosphorylation of PI3K and AKT, which were reversed by PIK3AP1 overexpression. At the same time, overexpression of PIK3AP1 also reversed the miR-1246 mimics-induced inhibition proliferative, migratory, and invasive activity, while promoting increases in apoptotic death, confirming that miR-1246 function was negatively correlated with that of PIK3AP1. Subsequently, we found that the miR-1246 mimics-induced inhibition of PI3K/AKT phosphorylation was reversed by the PI3K/AKT activator IGF-1. miR-1246 mimics inhibited proliferative, migratory, and invasive activity while promoting increases in apoptotic death, which were reversed by IGF-1. Furthermore, miR-1246 agomir can inhibit tumor growth in vivo. We confirmed that miR-1246 affects the signaling pathway of PI3K/AKT via targeting PIK3AP1 and inhibits the development of thyroid cancer. Thus, miR-1246 is a new therapeutic target for thyroid cancer.

scholarly journals Paeoniflorin Attenuates Inflammatory Pain by Inhibiting Microglial Activation and Akt-NF-κB Signaling in the Central Nervous System

2018 ◽  
Vol 47 (2) ◽  
pp. 842-850 ◽  
Author(s):  
Bo Hu ◽  
Guangtao Xu ◽  
Xiaomin Zhang ◽  
Long Xu ◽  
Hong Zhou ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Signaling Pathway ◽  
Inflammatory Pain ◽  
Microglial Activation ◽  
Enzyme Linked Immunosorbent Assay ◽  
Pain Model ◽  
The Central Nervous System

Background/Aims: Paeoniflorin (PF) is known to have anti-inflammatory and paregoric effects, but the mechanism underlying its analgesic effect remains unclear. The aim of this study was to clarify the effect of PF on Freund’s complete adjuvant (CFA)-induced inflammatory pain and explore the underlying molecular mechanism. Methods: An inflammatory pain model was established by intraplantar injection of CFA in C57BL/6J mice. After intrathecal injection of PF daily for 8 consecutive days, thermal and mechanical withdrawal thresholds, the levels of inflammatory factors TNF-α, IL-1β and IL-6, microglial activity, and the expression of Akt-NF-κB signaling pathway in the spinal cord tissue were detected by animal ethological test, cell culture, enzyme-linked immunosorbent assay, immunofluorescence histochemistry, and western blot. Results: PF inhibited the spinal microglial activation in the CFA-induced pain model. The production of proinflammatory cytokines was decreased in the central nervous system after PF treatment both in vivo and in vitro. PF further displayed a remarkable effect on inhibiting the activation of Akt-NF-κB signaling pathway in vivo and in vitro. Conclusion: These results suggest that PF is a potential therapeutic agent for inflammatory pain and merits further investigation.

scholarly journals Fabrication and Characterization of Paclitaxel and Resveratrol Loaded Soluplus Polymeric Nanoparticles for Improved BBB Penetration for Glioma Management

Polymers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 3210
Author(s):  
Talib Hussain ◽  
Sathishbabu Paranthaman ◽  
Syed Mohd Danish Rizvi ◽  
Afrasim Moin ◽  
Devegowda Vishakante Gowda ◽  
...  
Keyword(s):  
Polymeric Nanoparticles ◽  
C6 Glioma Cells ◽  
Brain Distribution ◽  
Distribution Study ◽  
Therapeutic Modalities ◽  
The Central Nervous System ◽  
Distribution Studies

Gliomas are one of the prominent cancers of the central nervous system with limited therapeutic modalities. The present investigation evaluated the synergistic effect of paclitaxel (PAX) and resveratrol (RESV)-loaded Soluplus polymeric nanoparticles (PNPs) against glioma cell lines along with in vivo pharmacokinetics and brain distribution study. PAX-RESV-loaded PNPs were prepared by the thin film hydration technique and optimized for different dependent and independent variables by using DoE (Design-Expert) software. The in vitro physiochemical characterization of prepared PAX-RESV-loaded PNPs exhibited appropriate particle size, PDI and % encapsulation efficiency. Cytotoxicity assay revealed that PTX-RESV loaded PNPs had a synergistic antitumor efficacy against C6 glioma cells compared with single and combined pure drugs. Finally, the pharmacokinetic and brain distribution studies in mice demonstrated that the PNPs significantly enhanced the bioavailability of PTX-RESV PNPs than pure PAX and RESV. Thus, the study concluded that PAX-RESV PNPs combination could significantly enhance anti-glioma activity, and this could be developed into a potential glioma treatment strategy.

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