A new acridine derivative induces cell cycle arrest and antiangiogenic effect on Ehrlich ascites carcinoma model

Mangueira, Vivianne Mendes; Batista, Tatianne Mota; Brito, Monalisa Taveira; Sousa, Tatyanna Kélvia Gomes de; Cruz, Ryldene Marques Duarte da; Abrantes, Renata Albuquerque de; Veras, Robson Cavalcante; Medeiros, Isac Almeida de; Medeiros, Karina Karla de Paula; Pereira, Ana Paula de Jesus Tomé; Serafim, Vanessa de Lima; Moura, Ricardo Olímpio de; Sobral, Marianna Vieira

doi:10.1016/j.biopha.2017.03.049

Cited by 21 publications

(23 citation statements)

References 30 publications

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“…Antiangiogenic therapy is an important target for antitumor drug action, since it prevents the emergence of new blood vessels that support tumor growth and induce metastasis [20]. Our data suggest that the AMTAC-17 mechanism of antitumor action involves an antiangiogenic effect, as previously reported for acridines [12].…”

Section: Biological Evaluationsupporting

confidence: 75%

“…The AMTAC-17 12.5-mg/kg dose was chosen to study the mechanism of antitumor action because no significant difference between the doses tested was observed. Literature data have shown the in vivo antitumor effects for acridine derivatives [12,13]. However, this is the first time that the mechanism of antitumor action of a spiro-acridine compound has been described.…”

Section: Biological Evaluationmentioning

confidence: 92%

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Antitumor Effect of a Novel Spiro-Acridine Compound is Associated with Up-Regulation of Th1-Type Responses and Antiangiogenic Action

et al. 2019

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Tumor cells have specific features, including angiogenesis induction, cell cycle dysregulation, and immune destruction evasion. By inducing a T helper type 2 (Th2) immune response, tumor cells may favor immune tolerance within the tumor, which allows progression of cancer growth. Drugs with potential antitumor activity are the spiro-acridines, which is a promising new class of acridine compounds. Herein, the novel spiro-acridine (E)-5 -oxo-1 -((3,4,5-trimethoxybenzylidene)amino)-1 ,5 -dihydro-10H-spiro[acridine-9,2 -pyrrole]-4 -carbonitrile (AMTAC-17) was synthesized and tested for antitumor effects. Toxicity evaluation was performed in mice after acute treatment (2000 mg/kg, intraperitoneally, i.p.). The Ehrlich ascites carcinoma model was used to investigate the antitumor activity of AMTAC-17 (12.5, 25, or 50 mg/kg, i.p.) after seven days of treatment. Effects on the cell cycle, angiogenesis, and inflammatory responses were investigated. LD 50 (lethal dose 50%) was estimated to be higher than 5000 mg/kg. AMTAC-17 reduced the Ehrlich tumor's total viable cancer cells count and peritumoral micro-vessels density, and induced an increase in the sub-G1 peak. Additionally, there was an increase of Th1 cytokine profile levels (IL-1β, TNF-α, and IL-12). In conclusion, the spiro-acridine compound AMTAC-17 presents low toxicity, and its in vivo antitumor effect involves modulation of the immune system to a cytotoxic Th1 profile and a reduction of tumor angiogenesis.

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Section: Biological Evaluationsupporting

confidence: 75%

Section: Biological Evaluationmentioning

confidence: 92%

Antitumor Effect of a Novel Spiro-Acridine Compound is Associated with Up-Regulation of Th1-Type Responses and Antiangiogenic Action

et al. 2019

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“…ACS03 reduced the tumor volume and cell viability, indicating significant in vivo activity of this compound. Our data corroborate the literature results of separate acridine and thiophene compounds showing an antitumor effect on the Ehrlich ascites carcinoma model [42,43].…”

Section: Discussionsupporting

confidence: 92%

Toxicity and Antitumor Activity of a Thiophene–Acridine Hybrid

et al. 2019

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The antitumor effects of thiophene and acridine compounds have been described; however, the clinical usefulness of these compounds is limited due to the risk of high toxicity and drug resistance. The strategy of molecular hybridization presents the opportunity to develop new drugs which may display better target affinity and less serious side effects. Herein, 2-((6-Chloro-2-methoxy-acridin-9-yl)amino)-5,6,7,8-tetrahydro-4H-cyclohepta[b]-thiophene-3-carbonitrile (ACS03), a hybrid thiophene–acridine compound with antileishmanial activity, was tested for toxicity and antitumor activity. The toxicity was evaluated in vitro (on HaCat and peripheral blood mononuclear cells) and in vivo (zebrafish embryos and acute toxicity in mice). Antitumor activity was also assessed in vitro in HCT-116 (human colon carcinoma cell line), K562 (chronic myeloid leukemic cell line), HL-60 (human promyelocytic leukemia cell line), HeLa (human cervical cancer cell line), and MCF-7 (breast cancer cell line) and in vivo (Ehrlich ascites carcinoma model). ACS03 exhibited selectivity toward HCT-116 cells (Half maximal inhibitory concentration, IC50 = 23.11 ± 1.03 µM). In zebrafish embryos, ACS03 induced an increase in lactate dehydrogenase, glutathione S-transferase, and acetylcholinesterase activities. The LD50 (lethal dose 50%) value in mice was estimated to be higher than 5000 mg/kg (intraperitoneally). In vivo, ACS03 (12.5 mg/kg) induced a significant reduction in tumor volume and cell viability. In vivo antitumor activity was associated with the nitric oxide cytotoxic effect. In conclusion, significant antitumor activity and weak toxicity were recorded for this hybrid compound, characterizing it as a potential anticancer compound.

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“…The new analogue amsacrine (ACS-AZ10) demonstrated greater antitumor activity compared to amsarkin due to a significant decrease in tumor mass and volume, viability of tumor cells and their total number. The arrest of the cell cycle and a decrease in the density of microvessels were also noted, which indicates its antiangiogenic effect [6].…”

Section: Medical Sciencesmentioning

confidence: 95%

Study of the Influence of Different Factors on Tumor Growth on a Model of Transplanted Ehrlich’s Mammary Gland Adenocarcinoma

Savluchinskaya¹,

Рыжова²,

Deryagina³

et al. 2021

EJNH

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When conducting preclinical studies, it is necessary to use appropriate experimental models, which can further increase the effectiveness of anticancer therapy. The review showed the relevance of using Ehrlich's mammary gland adenocarcinoma (EAC) model for this purpose, represented by two strains (subcutaneous and ascites). In this model, a large number of substances have been successfully tested and their potential antitumor effect has been identified. The use of EAC has been expanded to include the study of agents such as tumor necrosis factor, as well as nanoparticles as targeted drugs. This model was used to study the unstructured protein apoptin of the chicken anemia virus (ApoA-1), which is capable of causing the death of tumor cells. Molecular mechanisms of carcinogenic action, including expression, angiogenesis and apoptosis in tumors, were studied using the example of the investigated factors tested on the EAC. The cell cycle and the role of macrophages in the tumor growth and inflammation have been investigated under the influence of potential anticancer agents. The review provides examples of the use of the EAC model in testing natural drugs that help overcome the toxicity and drug resistance of chemotherapeutic agents. The successful use of EAC has been shown in the study of various types of anticancer therapy (photodynamic, radiation, magnetic).

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A new acridine derivative induces cell cycle arrest and antiangiogenic effect on Ehrlich ascites carcinoma model

Cited by 21 publications

References 30 publications

Antitumor Effect of a Novel Spiro-Acridine Compound is Associated with Up-Regulation of Th1-Type Responses and Antiangiogenic Action

Antitumor Effect of a Novel Spiro-Acridine Compound is Associated with Up-Regulation of Th1-Type Responses and Antiangiogenic Action

Toxicity and Antitumor Activity of a Thiophene–Acridine Hybrid

Study of the Influence of Different Factors on Tumor Growth on a Model of Transplanted Ehrlich’s Mammary Gland Adenocarcinoma

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