scholarly journals MM-129 as a Novel Inhibitor Targeting PI3K/AKT/mTOR and PD-L1 in Colorectal Cancer

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3203
Author(s):  
Justyna Magdalena Hermanowicz ◽  
Krystyna Pawlak ◽  
Beata Sieklucka ◽  
Robert Czarnomysy ◽  
Iwona Kwiatkowska ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Antitumor Activity ◽  
Drug Candidate ◽  
Signal Molecules ◽  
Triazine Derivative ◽  
Cycle Arrest ◽  
Extracellular Signal ◽  
Self Tolerance ◽  
Dual Mechanism

Background and aims: The purpose of the present study was to examine the pharmacodynamics features of MM-129 (1,2,4-triazine derivative) as a novel promising drug candidate against colon cancer. Methods: MM-129 was assessed for antitumor activity through an in vivo study on Cby.Cg-Foxn1nu/cmdb mice. The mechanistic studies investigated cellular affinity of a new 1,2,4-triazine derivative by measuring levels of intracellular/extracellular signal molecules participating in tumorigenesis. Results: The results revealed that MM-129 significantly reduced tumor growth in mice challenged with DLD-1 and HT-29 cells. It exerted the ability to inhibit intracellular molecules promoting tumorigenesis and inducing cell cycle arrest, like Akt, mTOR, and CDK2. Simultaneously, it was able to downregulate PD-L1 expression, which involves immunological self-tolerance. Combined administration of MM-129 and 5-fluorouracil (5-FU) additionally amplified these effects, which were manifest as an increase population of cells in the G0/G1 phase. Conclusions: A novel 1,2,4-triazine derivative with a dual mechanism of antitumor activity—MM-129, may act as a chemosensitizer, overcoming chemoresistance against 5-FU, the first-line agent in the chemotherapy of colon cancer.

scholarly journals Design, synthesis and pharmacological evaluation of novel 2-chloro-3-(1H-benzo[d]imidazol-2-yl)quinoline derivatives as antitumor agents: in vitro and in vivo antitumor activity, cell cycle arrest and apoptotic response

RSC Advances ◽  
2018 ◽  
Vol 8 (43) ◽  
pp. 24376-24385 ◽  
Author(s):  
Wen-Bin Kuang ◽  
Ri-Zhen Huang ◽  
Yi-Lin Fang ◽  
Gui-Bin Liang ◽  
Chen-Hui Yang ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Antitumor Agents ◽  
Quinoline Derivatives ◽  
Apoptotic Response ◽  
Design Synthesis ◽  
Cycle Arrest ◽  
In Vivo Antitumor Activity ◽  
Combination Principle

A series of novel 2-chloro-3-(1H-benzo[d]imidazol-2-yl)quinoline derivatives were designed and synthesized as antitumor agents under the combination principle. The antitumor activity and mechanisms were then evaluated.

In vitro and in vivo antitumor activity of Yerba Mate extract in colon cancer models

2020 ◽  
Vol 85 (7) ◽  
pp. 2186-2197 ◽  
Author(s):  
Rocio S. Garcia‐Lazaro ◽  
Humberto Lamdan ◽  
Lorena G. Caligiuri ◽  
Norailys Lorenzo ◽  
Andrea L. Berengeno ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Antitumor Activity ◽  
Yerba Mate ◽  
Cancer Models ◽  
In Vivo Antitumor Activity

scholarly journals In Vitro and in Vivo antitumor activity and the mechanism of siphonodictyal B in human colon cancer cells

2019 ◽  
Vol 8 (12) ◽  
pp. 5662-5672 ◽  
Author(s):  
Sonoko Chikamatsu ◽  
Ken Saijo ◽  
Hiroo Imai ◽  
Koichi Narita ◽  
Yoshifumi Kawamura ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Antitumor Activity ◽  
Cancer Cells ◽  
Human Colon ◽  
Colon Cancer Cells ◽  
Human Colon Cancer ◽  
In Vivo Antitumor Activity ◽  
Human Colon Cancer Cells

scholarly journals IN VIVO ANTITUMOR ACTIVITY OF PHYTOCHEMICAL PITC-2 OBTAINED FROM TISSUE CULTURED PLANT PLUCHEA INDICA ON SARCOMA-180 SOLID TUMOR MICE MODEL

2018 ◽  
Vol 11 (4) ◽  
pp. 211
Author(s):  
Soumita Goswami ◽  
Souvik Debnath ◽  
Saumen Karan ◽  
Tapan Kumar Chatterjee
Keyword(s):  
Antitumor Activity ◽  
Solid Tumor ◽  
Sarcoma 180 ◽  
Tumor Cell Proliferation ◽  
Mice Model ◽  
Ki 67 ◽  
Cycle Arrest ◽  
In Vivo Antitumor Activity ◽  
G1 Cell Cycle Arrest

 Objective: PITC-2 was isolated from the methanolic root extract of tissue cultured medicinal plant Pluchea indica (L.) Less. PITC-2 is a thiophene derivative which is 2-(Prop-1-ynyl)-5(5,6-dihydroxyhexa-1,3-diynyl)-thiophene. The main objective of the study is to evaluate the in vivo antitumor activity of PITC 2 against sarcoma-180 cancer cell in Swiss albino mice.Methods: The antitumor activity was evaluated by treatment with PITC-2 at a dose of 2.5 and 5 mg/kg b.w for 21 days on sarcoma-180 mice model. Cell viability was studied using 3-(4, 5- dimethylthiazol -2-yl)-2, 5-diphenyl tetrazolium bromide assay and cell apoptosis, G1 cell cycle arrest and reduction in tumor cell proliferation were evaluated by histopathological analysis and Bcl-2, cyclic-D1, and Ki-67 protein expression through immunohistochemistry study.Results: Precisely, PITC-2 had a cytotoxic effect on various in vitro cancer cells. Significant decreases in solid tumor volume and weight along with increase lifespan also observed. The histopathological and immunohistopathological examination indicates that PITC-2 induces apoptosis, typical morphological changes and suppresses tumor cell proliferation along with G1 cell cycle arrest through the downregulation of the intratumoral expression of Bcl-2, cyclic D1, and Ki-67 and thus highlighting antiproliferative and apoptotic properties against sarcoma-180 in vivo solid tumor model.Conclusion: The present results clearly demonstrate that PITC-2 significantly inhibits sarcoma-180 cell growth in a dose-dependent manner in in vivo mice model. Besides this, the study reveals a comprehensive perception of the possible mechanism behind the antitumor activity of PITC-2 by significant changes in the morphological, hematological, biochemical parameters in sarcoma-180 cells.

scholarly journals Solanum lyratumExtracts Induce Extrinsic and Intrinsic Pathways of Apoptosis in WEHI-3 Murine Leukemia Cells and Inhibit Allograft Tumor

2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Jai-Sing Yang ◽  
Chia-Chun Wu ◽  
Chao-Lin Kuo ◽  
Yu-Hsuan Lan ◽  
Chin-Chung Yeh ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Molecular Mechanisms ◽  
Fas Ligand ◽  
Leukemia Cells ◽  
Cycle Arrest ◽  
Phase Arrest ◽  
Apoptotic Pathways ◽  
Murine Leukemia

We investigated the molecular mechanisms of cell cycle arrest and apoptotic death induced bySolanum lyratumextracts (SLE) or diosgenin in WEHI-3 murine leukemia cellsin vitroand antitumor activityin vivo. Diosgenin is one of the components of SLE. Our study showed that SLE and diosgenin decreased the viable WEHI-3 cells and inducedG0/G1phase arrest and apoptosis in concentration- or time-dependent manners. Both reagents increased the levels of ROS production and decreased the mitochondrial membrane potential (ΔΨm). SLE- and diosgenin-triggered apoptosis is mediated through modulating the extrinsic and intrinsic signaling pathways. Intriguingly, the p53 inhibitor (pifithrin-α), anti-Fas ligand (FasL) mAb, and specific inhibitors of caspase-8 (z-IETD-fmk), caspase-9 (z-LEHD-fmk), and caspase-3 (z-DEVD-fmk) blocked SLE- and diosgenin-reduced cell viability of WEHI-3 cells. Thein vivostudy demonstrated that SLE has marked antitumor efficacy against tumors in the WEHI-3 cell allograft model. In conclusion, SLE- and diosgenin-inducedG0/G1phase arrest and triggered extrinsic and intrinsic apoptotic pathways via p53 activation in WEHI-3 cells. SLE also exhibited antitumor activityin vivo. Our findings showed that SLE may be potentially efficacious in the treatment of leukemia in the future.

Anti-Colon Cancer Effects of 6-Shogaol Through G2/M Cell Cycle Arrest by p53/p21-cdc2/cdc25A Crosstalk

2015 ◽  
Vol 43 (04) ◽  
pp. 743-756 ◽  
Author(s):  
Lian-Wen Qi ◽  
Zhiyu Zhang ◽  
Chun-Feng Zhang ◽  
Samantha Anderson ◽  
Qun Liu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Colon Cancer ◽  
Cell Cycle Arrest ◽  
Strong Support ◽  
Cancer Chemoprevention ◽  
M Cell ◽  
Cycle Arrest ◽  
Hct 116 ◽  
Hct 116 Cells

Chemopreventive agents can be identified from botanicals. Recently, there has been strong support for the potential of 6-shogaol, a natural compound from dietary ginger (Zingiber officinale), in cancer chemoprevention. However, whether 6-shogaol inhibits the growth of colorectal tumors in vivo remains unknown, and the underlying anticancer mechanisms have not been well characterized. In this work, we observed that 6-shogaol (15 mg/kg) significantly inhibited colorectal tumor growth in a xenograft mouse model. We show that 6-shogaol inhibited HCT-116 and SW-480 cell proliferation with IC50 of 7.5 and 10 μM, respectively. Growth of HCT-116 cells was arrested at the G2/M phase of the cell cycle, primarily mediated by the up-regulation of p53, the CDK inhibitor p21waf1/cip1 and GADD45α, and by the down-regulation of cdc2 and cdc25A. Using p53-/- and p53+/+ HCT-116 cells, we confirmed that p53/p21 was the main pathway that contributed to the G2/M cell cycle arrest by 6-shogaol. 6-Shogaol induced apoptosis, mainly through the mitochondrial pathway, and the bcl-2 family might act as a key regulator. Our results demonstrated that 6-shogaol induces cancer cell death by inducing G2/M cell cycle arrest and apoptosis. 6-Shogaol could be an active natural product in colon cancer chemoprevention.

Delivery of Sorafenib and Metformin Against Hepatocellular Carcinoma with Amphiphilic Polypeptide-based Micelles

2021 ◽  
Author(s):  
Lanqing Cao ◽  
Guangmeng Xu ◽  
Hongyu He ◽  
Jiannan Li
Keyword(s):  
Mapk Pathway ◽  
Synergistic Effects ◽  
Mitogen Activated Protein Kinase ◽  
High Recurrence Rate ◽  
Extracellular Signal Regulated Kinase ◽  
Cycle Arrest ◽  
Extracellular Signal ◽  
Mitogen Activated Protein ◽  
Poly Ethylene

Abstract Hepatoma is a common clinical disease with poor prognosis and a high recurrence rate. Chemotherapy is important for hepatoma treatment because only a small amount of hepatoma patients are suitable for local resection, and the effects of transarterial chemoembolization (TACE) are unsatisfactory. But many limitations restrict further application of chemotherapy. In this study, sorafenib (Sor) and metformin (Met) co-loaded poly(ethylene glycol)-block-poly(L-glutamic acid-co-L-phenylalanine) (mPEG-b-P(Glu-co-Phe)) micelles were developed. Sor is a common molecular target agent which can inhibit the mitogen-activated protein kinase (MAPK) pathway to treat hepatoma clinically. Met can also regulate the MAPK pathway and inhibit the expression of the phosphorylated extracellular signal-regulated kinase (p-ERK). Moreover, both Sor and Met play important roles in cell cycle arrest. The integration of these two drugs aims to achieve synergistic effects against hepatoma. The micelles can be targeted to cancer cells and possess longer blood circulation time. The two agents can be released rapidly in the tumor sites. Both orthotopic and patient-derived xenograft (PDX) hepatoma models were developed to analyze the treatment efficacy of the Sor and Met loaded micelles. The in vivo study showed that the micelles can prevent hepatoma progression by inhibiting the expressions of p-ERK and cyclin D1. This study indicated that the Sor/Met-loaded micelles are suitable for hepatoma treatment.

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