Anti-cancer effects of the aqueous extract of Orostachys japonica A. Berger on 5-fluorouracil-resistant colorectal cancer via MAPK signalling pathways in vitro and in vivo

2021 ◽  
pp. 114412
Author(s):  
Jung Woo Kim ◽  
Sang Hee Kim ◽  
Ramesh Mariappan ◽  
Daeun Moon ◽  
Jinu Kim ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Aqueous Extract ◽  
Signalling Pathways ◽  
Anti Cancer ◽  
Mapk Signalling

scholarly journals New Anti-Cancer Strategy to Suppress Colorectal Cancer Growth Through Inhibition of ATG4B and Lysosome Function

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1523 ◽  
Author(s):  
Yuanyuan Fu ◽  
Qianqian Gu ◽  
Li Luo ◽  
Jiecheng Xu ◽  
Yuping Luo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Therapy ◽  
Therapeutic Strategy ◽  
Screening Method ◽  
Cancer Drug ◽  
Autophagic Flux ◽  
Single Target ◽  
Anti Cancer

Autophagy inhibition has been proposed to be a potential therapeutic strategy for cancer, however, few autophagy inhibitors have been developed. Recent studies have indicated that lysosome and autophagy related 4B cysteine peptidase (ATG4B) are two promising targets in autophagy for cancer therapy. Although some inhibitors of either lysosome or ATG4B were reported, there are limitations in the use of these single target compounds. Considering multi-functional drugs have advantages, such as high efficacy and low toxicity, we first screened and validated a batch of compounds designed and synthesized in our laboratory by combining the screening method of ATG4B inhibitors and the identification method of lysosome inhibitors. ATG4B activity was effectively inhibited in vitro. Moreover, 163N inhibited autophagic flux and caused the accumulation of autolysosomes. Further studies demonstrated that 163N could not affect the autophagosome-lysosome fusion but could cause lysosome dysfunction. In addition, 163N diminished tumor cell viability and impaired the development of colorectal cancer in vivo. The current study findings indicate that the dual effect inhibitor 163N offers an attractive new anti-cancer drug and compounds having a combination of lysosome inhibition and ATG4B inhibition are a promising therapeutic strategy for colorectal cancer therapy.

scholarly journals A Review of the Role of Neurotensin and Its Receptors in Colorectal Cancer

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Shengyang Qiu ◽  
Gianluca Pellino ◽  
Francesca Fiorentino ◽  
Shahnawaz Rasheed ◽  
Ara Darzi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Animal Studies ◽  
In Vivo Studies ◽  
Signalling Pathways ◽  
Diagnostic Biomarker ◽  
Gi Tract ◽  
Cellular Receptors

Neurotensin (NTS) is a physiologically occurring hormone which affects the function of the gastrointestinal (GI) tract. In recent years, NTS, acting through its cellular receptors (NTSR), has been implicated in the carcinogenesis of several cancers. In colorectal cancer (CRC), a significant body of evidence, from in vitro and in vivo studies, is available which elucidates the molecular biology of NTS/NTSR signalling and the resultant growth of CRC cells. There is growing clinical data from human studies which corroborate the role NTS/NTSR plays in the development of human CRC. Furthermore, blockade and modulation of the NTS/NTSR signalling pathways appears to reduce CRC growth in cell cultures and animal studies. Lastly, NTS/NTSR also shows potential of being utilised as a diagnostic biomarker for cancers as well as targets for functional imaging. We summarise the existing evidence and understanding of the role of NTS and its receptors in CRC.

In vitro and in vivo anti-cancer activity of tangeretin against colorectal cancer was enhanced by emulsion-based delivery system

2015 ◽  
Vol 15 ◽  
pp. 264-273 ◽  
Author(s):  
Yuwen Ting ◽  
Yi-Shiou Chiou ◽  
Min-Hsiung Pan ◽  
Chi-Tang Ho ◽  
Qingrong Huang
Keyword(s):  
Colorectal Cancer ◽  
Delivery System ◽  
Anti Cancer ◽  
Cancer Activity

scholarly journals Deoxypodophyllotoxin Exerts Anti-Cancer Effects on Colorectal Cancer Cells Through Induction of Apoptosis and Suppression of Tumorigenesis

2019 ◽  
Vol 20 (11) ◽  
pp. 2612 ◽  
Author(s):  
Chathurika D. B. Gamage ◽  
So-Yeon Park ◽  
Yi Yang ◽  
Rui Zhou ◽  
İsa Taş ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Apoptotic Pathway ◽  
Anti Cancer ◽  
Cervical Tumors ◽  
Skin Xenograft

Deoxypodophyllotoxin (DPT) is a cyclolignan compound that exerts anti-cancer effects against various types of cancers. DPT induces apoptosis and inhibits the growth of breast, brain, prostate, gastric, lung, and cervical tumors. In this study, we sought to determine the effect of DPT on cell proliferation, apoptosis, motility, and tumorigenesis of three colorectal cancer (CRC) cell lines: HT29, DLD1, and Caco2. DPT inhibited the proliferation of these cells. Specifically, the compound-induced mitotic arrest in CRC cells by destabilizing microtubules and activating the mitochondrial apoptotic pathway via regulation of B-cell lymphoma 2 (Bcl-2) family proteins (increasing Bcl-2 associated X (BAX) and decreasing B-cell lymphoma-extra-large (Bcl-xL)) ultimately led to caspase-mediated apoptosis. In addition, DPT inhibited tumorigenesis in vitro, and in vivo skin xenograft experiments revealed that DPT significantly decreased tumor size and tumor weight. Taken together, our results suggest DPT to be a potent compound that is suitable for further exploration as a novel chemotherapeutic for human CRC.

scholarly journals Ovarian signalling pathways regulated by leptin during the ovulatory process

Reproduction ◽  
2013 ◽  
Vol 146 (6) ◽  
pp. 647-658 ◽  
Author(s):  
María Paula Di Yorio ◽  
María Guillermina Bilbao ◽  
Ana María Biagini-Majorel ◽  
Alicia Graciela Faletti
Keyword(s):  
Signalling Pathways ◽  
Simultaneous Increase ◽  
Inhibitory Effects ◽  
Mapk Signalling ◽  
Dual Action ◽  
Socs3 Protein ◽  
Ovulatory Process ◽  
Different Levels

Leptin, a protein secreted by different tissues, is able to exert both stimulatory and inhibitory effects on the ovulatory process. Thus, we investigated whether these opposite effects involve changes in the ovarian signalling pathways in response to different levels of leptin. To this end, we performed both in vivo and in vitro assays using immature rats primed with gonadotrophins to induce ovulation. The acute treatment with leptin, which inhibits the ovulatory process, caused a significant decrease in the phosphorylation of both STAT3 and ERK1/2 and a simultaneous increase in suppressors of cytokine signalling 3 (SOCS3) protein. However, daily administration of a low dose of leptin, which induces the ovulatory process, showed increased phosphorylation of both STAT3 and ERK1/2 and a decreased expression of SOCS3 protein. Using ovarian explant cultures, we also found that leptin was able to activate both STAT3 and ERK1/2 at 10 ng/ml but only STAT3 at 300–500 ng/ml. In addition, at 100–300 ng/ml, leptin increased protein but not mRNA expression of SOCS3. The addition of specific inhibitors of JAK/STAT and MAPK signalling pathways suppressed both the increase and the decrease in leptin-induced progesterone secretion. These results indicate that i) different levels of leptin are able to regulate STAT3, ERK1/2 and SOCS3 at both intra- and extra-ovarian level and that ii) the dual action of leptin on steroidogenesis seems to occur, at least in part, through both the ERK and STAT cascades.

scholarly journals Activation of mitogen-activated protein kinases in satellite glial cells of the trigeminal ganglion contributes to substance P-mediated inflammatory pain

2019 ◽  
Vol 11 (3) ◽  
Author(s):  
Yanyan Zhang ◽  
Ning Song ◽  
Fei Liu ◽  
Jiu Lin ◽  
Mengke Liu ◽  
...  
Keyword(s):  
Substance P ◽  
Inflammatory Pain ◽  
Orofacial Pain ◽  
Signalling Pathways ◽  
Satellite Glial Cells ◽  
Tnf Α ◽  
Mapk Signalling ◽  
Mitogen Activated Protein

Abstract Inflammatory orofacial pain, in which substance P (SP) plays an important role, is closely related to the cross-talk between trigeminal ganglion (TG) neurons and satellite glial cells (SGCs). SGC activation is emerging as the key mechanism underlying inflammatory pain through different signalling mechanisms, including glial fibrillary acidic protein (GFAP) activation, phosphorylation of mitogen-activated protein kinase (MAPK) signalling pathways, and cytokine upregulation. However, in the TG, the mechanism underlying SP-mediated orofacial pain generated by SGCs is largely unknown. In this study, we investigated whether SP is involved in inflammatory orofacial pain by upregulating interleukin (IL)-1β and tumour necrosis factor (TNF)-α from SGCs, and we explored whether MAPK signalling pathways mediate the pain process. In the present study, complete Freund’s adjuvant (CFA) was injected into the whisker pad of rats to induce an inflammatory model in vivo. SP was administered to SGC cultures in vitro to confirm the effect of SP. Facial expression analysis showed that pre-injection of L703,606 (an NK-1 receptor antagonist), U0126 (an inhibitor of MAPK/extracellular signal-regulated kinase [ERK] kinase [MEK] 1/2), and SB203580 (an inhibitor of P38) into the TG to induce targeted prevention of the activation of the NK-1 receptor and the phosphorylation of MAPKs significantly suppressed CFA-induced inflammatory allodynia. In addition, SP promoted SGC activation, which was proven by increased GFAP, p-MAPKs, IL-1β and TNF-α in SGCs under inflammatory conditions. Moreover, the increase in IL-1β and TNF-α was suppressed by L703, 606, U0126 and SB203580 in vivo and in vitro. These present findings suggested that SP, released from TG neurons, activated SGCs through the ERK1/2 and P38 pathways and promoted the production of IL-1β and TNF-α from SGCs, contributing to inflammatory orofacial pain associated with peripheral sensitization.

Oleanolic Acid Inhibits Colorectal Cancer Angiogenesis by Blocking the VEGFR2 Signaling Pathway

2018 ◽  
Vol 18 (4) ◽  
pp. 583-590 ◽  
Author(s):  
Guoping Niu ◽  
Li Sun ◽  
Yunfeng Pei ◽  
Duping Wang
Keyword(s):  
Colorectal Cancer ◽  
Oleanolic Acid ◽  
Tumor Angiogenesis ◽  
Intracellular Signaling ◽  
Umbilical Vein ◽  
Herbal Medicines ◽  
Tube Formation ◽  
Anti Cancer

Background: Angiogenesis is a crucial process that regulated by multiple intracellular signaling pathways including MEK/ERK and JNK/SAPK. Thus, many inhibitors have developed to these pathways as anti-cancer therapeutic strategies. Oleanolic acid (OA) is a natural pentacyclic triterpenoic acid compound that present in various herbal medicines. It has been used as antitumor agent for various cancers including colorectal cancer (CRC), which attenuates angiogenesis. Objective: To study the molecular mechanism of OA suppressing angiogenesis. Method: The proliferation of human umbilical vein endothelial cells (HUVECs) was determined by MTT and the invasion and migration of them were measured by wound-healing Assay, transwell migration assay and tube formation assay. The xenograft mouse model was used to study the effect of OA blocking angiogenesis in vivo. The Western blot was used to checked the phosphorylation of VEGFR2. Results: OA attenuates HUVECs invasion, migration, tube formation and vascular sprouting. Moreover, OA suppresses HUVECs sprout and tube formation. Importantly, OA also blocks angiogenesis in HUVECs and colorectal cancer cells (HCT-116) both in vitro and in vivo. OA-dependent suppression of tumor angiogenesis mediated by blocking the phosphorylation of the vascular endothelial growth factor receptor-2 (VEGFR2) that results in inhibition of MEK/ERK/JNK pathway. Conclusion: Our results suggest that inhibition of tumor angiogenesis via the suppression VEGFR2 phosphorylation may be one of the underlying mechanisms by which OA exerts its anti-cancer effect.

scholarly journals Cyclooxygenase activity mediates colorectal cancer cell resistance to the omega-3 polyunsaturated fatty acid eicosapentaenoic acid

2020 ◽  
Author(s):  
Milene Volpato ◽  
Nicola Ingram ◽  
Sarah L Perry ◽  
Jade Spencer ◽  
Amanda D Race ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Fatty Acid ◽  
Omega 3 ◽  
Anti Cancer ◽  
Increased Sensitivity ◽  
Cox 2 ◽  
Human And Mouse ◽  
Cox 1

Abstract Purpose The naturally-occurring omega-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA) is safe, well-tolerated and inexpensive, making it an attractive anti-cancer intervention. However, EPA has only modest anti-colorectal cancer (CRC) activity, when used alone. Both cyclooxygenase (COX) isoforms metabolise EPA and are over-expressed in CRC cells. We investigated whether COX inhibition increases the sensitivity of CRC cells to growth inhibition by EPA. Methods A panel of 18 human and mouse CRC cell lines was used to characterize the differential sensitivity of CRC cells to the growth inhibitory effects of EPA. The effect of CRISPR-Cas9 genetic deletion and pharmacological inhibition of COX-1 and COX-2 on the anti-cancer activity of EPA was determined using in vitro and in vivo models. Results Genetic ablation of both COX isoforms increased sensitivity of CT26 mouse CRC cells to growth inhibition by EPA in vitro and in vivo. The non-selective COX inhibitor aspirin and the selective COX-2 inhibitor celecoxib increased sensitivity of several human and mouse CRC cell lines to EPA in vitro. However, in a MC38 mouse CRC cell tumour model, with dosing that mirrored low-dose aspirin use in humans, thereby producing significant platelet COX-1 inhibition, there was ineffective intra-tumoral COX-2 inhibition by aspirin and no effect on EPA sensitivity of MC38 cell tumours. Conclusion Cyclooxygenase inhibition by non-steroidal anti-inflammatory drugs represents a therapeutic opportunity to augment the modest anti-CRC activity of EPA. However, intra-tumoral COX inhibition is likely to be critical for this drug-nutrient interaction and careful tissue pharmacodynamic profiling is required in subsequent pre-clinical and human studies.

The Antitumor Activity of Betulinic Acid-Loaded Nanoliposomes Against Colorectal Cancer In Vitro and In Vivo via Glycolytic and Glutaminolytic Pathways

2020 ◽  
Vol 16 (2) ◽  
pp. 235-251
Author(s):  
Gang Wang ◽  
Yu-Zhu Wang ◽  
Yang Yu ◽  
Pei-Hao Yin ◽  
Ke Xu
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Cellular Uptake ◽  
Betulinic Acid ◽  
Anticancer Efficacy ◽  
Anti Cancer ◽  
Colorectal Cancer Cells ◽  
Cellular Apoptosis

The purpose of this study is to develop betulinic acid loaded nanoliposomes to improve the chemotherapy effect of colorectal cancer. The cellular uptake and anti-tumor effects of betulinic acid loaded nanoliposomes in vitro were characterized and evaluated, and their effects on glycolysis, glutamine decomposition and key anti-cancer targets were analyzed. Moreover, their anticancer efficacy was assessed in vivo. Compared with free betulinic acid in vitro, the cellular uptake and anti-tumor activity of betulinic acid-loaded nanoliposomes were significantly enhanced; these nanoliposomes significantly suppressed the proliferation and glucose uptake of colorectal cancer cells. Mechanistically, the anti-colorectal cancer effect of betulinic acid-loaded nanoliposomes was confirmed by their triggering of cellular apoptosis and regulating the potential glycolytic and glutaminolytic targets and pathways. After tumor proliferation was inhibited and colorectal cancer cells apoptosis, the anticancer effect of betulinic acid loaded nanoliposomes in vivo was significantly enhanced. All in all, betulinic acid loaded nanoliposomes are expected to be an effective drug delivery system for colorectal cancer treatment.

In vitro and in vivo Trypanocidal Effect of the Aqueous extract of the Leaves of Ochna Schweinfurthiana

2020 ◽  
Vol 4 (1) ◽  
pp. 47-51
Author(s):  
Eteme Enama S ◽  
Messi A N ◽  
Mahob R J ◽  
Siama A ◽  
Njan Nloga A M
Keyword(s):  
Aqueous Extract
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