In Vitro and In Vivo Antitumor Activity of [Pt(O,O′-acac)(γ-acac)(DMS)] in Malignant Pleural Mesothelioma

AbstractMalignant pleural mesothelioma (MPM) is an aggressive neoplasm originating from the pleura. Non-epithelioid (biphasic and sarcomatoid) MPM are particularly resistant to therapy. We investigated the role of the GITR-GITRL pathway in mediating the resistance to therapy. We found that GITR and GITRL expressions were higher in the sarcomatoid cell line (CRL5946) than in non-sarcomatoid cell lines (CRL5915 and CRL5820), and that cisplatin and Cs-137 irradiation increased GITR and GITRL expressions on tumor cells. Transcriptome analysis demonstrated that the GITR-GITRL pathway was promoting tumor growth and inhibiting cell apoptosis. Furthermore, GITR+ and GITRL+ cells demonstrated increased spheroid formation in vitro and in vivo. Using patient derived xenografts (PDXs), we demonstrated that anti-GITR neutralizing antibodies attenuated tumor growth in sarcomatoid PDX mice. Tumor immunostaining demonstrated higher levels of GITR and GITRL expressions in non-epithelioid compared to epithelioid tumors. Among 73 patients uniformly treated with accelerated radiation therapy followed by surgery, the intensity of GITR expression after radiation negatively correlated with survival in non-epithelioid MPM patients. In conclusion, the GITR-GITRL pathway is an important mechanism of autocrine proliferation in sarcomatoid mesothelioma, associated with tumor stemness and resistance to therapy. Blocking the GITR-GITRL pathway could be a new therapeutic target for non-epithelioid mesothelioma.

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Synthesis, in vitro and in vivo antitumor activity of symmetrical bis-Schiff base derivatives of isatin

European Journal of Medicinal Chemistry ◽

10.1016/j.ejmech.2013.04.040 ◽

2014 ◽

Vol 74 ◽

pp. 742-750 ◽

Cited By ~ 57

Author(s):

Chengyuan Liang ◽

Juan Xia ◽

Dong Lei ◽

Xiang Li ◽

Qizheng Yao ◽

...

Keyword(s):

Schiff Base ◽

Antitumor Activity ◽

Schiff Base Derivatives ◽

In Vivo Antitumor Activity ◽

Derivatives Of

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Knockdown of Ras-Related Protein 25 (Rab25) Inhibits the In Vitro Cytotoxicity and In Vivo Antitumor Activity of Human Glioblastoma Multiforme Cells

Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics ◽

10.3727/096504016x14736286083065 ◽

2017 ◽

Vol 25 (3) ◽

pp. 331-340 ◽

Cited By ~ 4

Author(s):

Bingqian Ding ◽

Bei Cui ◽

Ming Gao ◽

Zhenjiang Li ◽

Chenyang Xu ◽

...

Keyword(s):

Glioblastoma Multiforme ◽

Antitumor Activity ◽

In Vitro Cytotoxicity ◽

Related Protein ◽

Human Glioblastoma ◽

Human Glioblastoma Multiforme ◽

In Vivo Antitumor Activity

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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 ◽

10.1039/c8ra04640a ◽

2018 ◽

Vol 8 (43) ◽

pp. 24376-24385 ◽

Cited By ~ 4

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.

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„IN VITRO“ AND „IN VIVO“ ANTITUMOR ACTIVITY OF PLATINUM(II) COMPLEXES WITH MALONIC ACID ON BREAST AND COLORECTAL CARCINOMA CELL LINES

10.46793/iccbi21.293f ◽

2021 ◽

Author(s):

Andjela Franich ◽

◽

Milica Dimitrijević Stojanović ◽

Snežana Rajković ◽

Marina Jovanović ◽

...

Keyword(s):

Antitumor Activity ◽

Colorectal Carcinoma ◽

Cell Lines ◽

Tumor Model ◽

Carcinoma Cells ◽

Spectroscopic Techniques ◽

Murine Cell Line ◽

In Vivo Antitumor Activity

Four Pt(II) complexes of the general formula [Pt(L)(5,6-epoxy-1,10-phen)], where L is anion of malonic (mal, Pt1), 2-methylmalonic (Me-mal, Pt2), 2,2-dimethylmalonic (Me2-mal, Pt3) or 1,1- cyclobutanedicarboxylic (CBDCA, Pt4) acid while 5,6-epoxy-1,10-phen is bidentately coordinated 5,6-epoxy-5,6-dihydro-1,10-phenanthroline were synthesized and characterized by elemental microanalysis, IR, UV-Vis and NMR (1H and 13C) spectroscopic techniques. In vitro anticancer activity of novel platinum(II) complexes have been investigated on human and murine cancer cell lines, as well as normal murine cell line by MTT assay. The obtained results indicate that studied platinum(II) complexes exhibited strong cytotoxic activity against murine breast carcinoma cells (4T1), human (HCT116) and murine (CT26) colorectal carcinoma cells. Complex Pt3 display stronger selectivity toward carcinoma cells in comparison to other tested platinum(II) complexes exhibiting beneficial antitumor activity mainly via the induction of apoptosis, as well as inhibition of cell proliferation and migration. Further study showed that Pt3 complex also carry significant in vivo antitumor activity in orthotopical 4T1 tumor model without detected liver, kidney, lung, and heart toxicity. All results imply that these novel platinum(II) complexes have a good anti-tumor effect on breast and colorectal cancer in vivo and in vitro and the affinity to become possible candidates for treatment in anticancer therapy.

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Cytotoxicity and Antitumor Activity of Platinum(II) Complexes of Aromatic and Cycloalkanecarboxylic Acid Hydrazides

Zeitschrift für Naturforschung C ◽

10.1515/znc-1997-1-209 ◽

1997 ◽

Vol 52 (1-2) ◽

pp. 49-54 ◽

Cited By ~ 7

Author(s):

Daniel N. Kushev ◽

Nadejda C. Spassovska ◽

Svetoslav I. Taxirov ◽

Konstantin C. Grancharov

Keyword(s):

Antitumor Activity ◽

Acid Hydrazide ◽

In Vitro Cytotoxicity ◽

Macromolecular Synthesis ◽

H Nmr ◽

Antineoplastic Effect ◽

In Vivo Antitumor Activity ◽

Friend Leukemia

AbstractNew platinum(II) complexes of cyclohexanecarboxylic acid hydrazide (chcah) were synthesized and characterized by elemental analysis, IR. and 1H NMR spectra. Their inhibitory effects on cell growth and macromolecular synthesis of Friend leukemia cells in culture as well as the in vivo antitumor activity towards L1210 leukemia in mice were compared with those of complexes containing differently substituted aromatic acid hydrazides. Some of the complexes exhibited antineoplastic activity. No correlation between the in vitro cytotoxicity and the in vivo antitumor activity was found. However, there was a relationship between the in vitro macromolecular synthesis inhibition profile and the in vivo antineoplastic effect, similar to that of cisplatin. On the other hand, only agents containing one ammine ligand were active in vivo. The substitution of the aromatic ring by a cycloalkane residue increased significantly the antitumor effect, with [Pt(NH3)(chcah)Cl2] being the most active compound in this study.

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In vitro and in vivo antitumor activity of deoxyelephantopin from a potential medicinal plant Elephantopus scaber against Ehrlich ascites carcinoma

Biocatalysis and Agricultural Biotechnology ◽

10.1016/j.bcab.2019.101106 ◽

2019 ◽

Vol 19 ◽

pp. 101106 ◽

Cited By ~ 1

Author(s):

Farha Arakkaveettil Kabeer ◽

Dhanya Sethumadhavan Rajalekshmi ◽

Mangalam Sivasankaran Nair ◽

Remani Prathapan

Keyword(s):

Antitumor Activity ◽

Medicinal Plant ◽

Ehrlich Ascites Carcinoma ◽

In Vivo Antitumor Activity ◽

Ehrlich Ascites ◽

Elephantopus Scaber

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Targeted Brain Tumor Therapy by Inhibiting the MDM2 Oncogene: In Vitro and In Vivo Antitumor Activity and Mechanism of Action

Cells ◽

10.3390/cells9071592 ◽

2020 ◽

Vol 9 (7) ◽

pp. 1592

Author(s):

Surendra R. Punganuru ◽

Viswanath Arutla ◽

Wei Zhao ◽

Mehrdad Rajaei ◽

Hemantkumar Deokar ◽

...

Keyword(s):

Brain Tumor ◽

Antitumor Activity ◽

Cell Lines ◽

Tumor Therapy ◽

Single Agent ◽

M Cell ◽

In Vivo Antitumor Activity ◽

The Brain

There is a desperate need for novel and efficacious chemotherapeutic strategies for human brain cancers. There are abundant molecular alterations along the p53 and MDM2 pathways in human glioma, which play critical roles in drug resistance. The present study was designed to evaluate the in vitro and in vivo antitumor activity of a novel brain-penetrating small molecule MDM2 degrader, termed SP-141. In a panel of nine human glioblastoma and medulloblastoma cell lines, SP-141, as a single agent, potently killed the brain tumor-derived cell lines with IC50 values ranging from 35.8 to 688.8 nM. Treatment with SP-141 resulted in diminished MDM2 and increased p53 and p21cip1 levels, G2/M cell cycle arrest, and marked apoptosis. In intracranial xenograft models of U87MG glioblastoma (wt p53) and DAOY medulloblastoma (mutant p53) expressing luciferase, treatment with SP-141 caused a significant 4- to 9-fold decrease in tumor growth in the absence of discernible toxicity. Further, combination treatment with a low dose of SP-141 (IC20) and temozolomide, a standard anti-glioma drug, led to synergistic cell killing (1.3- to 31-fold) in glioma cell lines, suggesting a novel means for overcoming temozolomide resistance. Considering that SP-141 can be taken up by the brain without the need for any special delivery, our results suggest that SP-141 should be further explored for the treatment of tumors of the central nervous system, regardless of the p53 status of the tumor.

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