scholarly journals In Vitro and In Vivo Antitumor Activity of Indolo[2,3-b] Quinolines, Natural Product Analogs from Neocryptolepine Alkaloid

Molecules ◽  
2021 ◽  
Vol 26 (3) ◽  
pp. 754
Author(s):  
Najla Altwaijry ◽  
Samah El-Ghlban ◽  
Ibrahim E.-T. El Sayed ◽  
Mohamed El-Bahnsawye ◽  
Asmaa I. Bayomi ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Antitumor Activity ◽  
Apoptotic Cell ◽  
Ehrlich Ascites Carcinoma ◽  
Immunological Study ◽  
In Vivo Evaluation ◽  
Reference Drug ◽  
Dpph Method

Neocryptolepine (5-methyl-5H-indolo[2,3-b] quinoline) analogs were synthesized and evaluated in vitro and in vivo for their effect versus Ehrlich ascites carcinoma (EAC). The analogs showed stronger cytotoxic activity against EAC cells than the reference drug. The in vivo evaluation of the target compounds against EAC-induced solid tumor in the female albino Swiss mice revealed a remarkable decrease in the tumor volume (TV) and hepatic lipid peroxidation. A noticeable increase of both superoxide dismutase (SOD) and catalase (CAT) levels was reported (p < 0.001), which set-forth proof of their antioxidant effect. In addition, the in vitro antioxidant activity of the neocryptolepine analogs was screened out using the DPPH method and showed promising activities activity. The histopathological investigations affirmed that the tested analogs have a remarkable curative effect on solid tumors with minimal side-effect on the liver. The study also includes illustrated mechanism of the antitumor activity at the cell level by flow cytometry. The cell cycle analysis showed that the neocryptolepine analogs extensively increase the aggregation of tumor cells in three phases of the cell cycle (G0/G1, S and G2/M) with the emergence of a hypo-diploid DNA content peak (sub-G1) in the cell cycle experiments, which is a clear-cut for the apoptotic cell population. Furthermore, the immunological study manifested a significant elevation in splenic lymphocyte count (p < 0.001) with the elevation of the responsiveness of lymphocytes to phytohemagglutinin (PHA). These results indicate that these naturally-based neocryptolepine alkaloids exhibit marked antitumor activity in vivo and represent an important lead in the development of natural-based anticancer drugs.

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

Molecules ◽  
2019 ◽  
Vol 25 (1) ◽  
pp. 29 ◽  
Author(s):  
Daiana K. Frade Silva ◽  
Sâmia S. Duarte ◽  
Thaís M. H. Lisboa ◽  
Rafael C. Ferreira ◽  
Ana Luíza de O. Lopes ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Antitumor Activity ◽  
Tumor Cells ◽  
Antitumor Effect ◽  
Inflammatory Responses ◽  
Lethal Dose ◽  
Ehrlich Ascites Carcinoma ◽  
Antitumor Effects ◽  
Th2 Immune Response

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. LD50 (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.

scholarly journals In vitro and in vivo evaluation of antitumor activity of methanolic extract of Argyreia nervosa leaves on Ehrlich ascites carcinoma

2015 ◽  
Vol 10 (2) ◽  
pp. 399
Author(s):  
Bhawna Sharma ◽  
Isha Dhamija ◽  
Sandeep Kumar ◽  
Hema Chaudhary
Keyword(s):  
Antitumor Activity ◽  
Solid Tumor ◽  
Methanolic Extract ◽  
Ehrlich Ascites Carcinoma ◽  
Ehrlich Ascites ◽  
Wide Range ◽  
Antioxidant Parameters ◽  
Argyreia Nervosa

<p>The herb of importance like <em>Argyreia nervosa</em> has shown wide range of pharmacological activities. Its methanolic extract of <em>A. nervosa</em> has been explored against Ehrlich ascites carcinoma (EAC) induced liquid and solid tumor in mice. Liquid and solid tumors were induced by intraperitoneal and subcutaneous transplantation of EAC cells in Balb/C mice. Significant and dose dependant results are observed when the mice are sacrificed on 15<sup>th</sup> day for estimation of tumor proliferation, hematological, biochemical and hepatic antioxidant parameters. Mean survival time (days) was increased to 36.5 from 20.5 extract treated mice. The extract also showed a decrease (p&lt;0.001) in body weight and percentage reduction in tumor volume respectively when it was evaluated in solid tumor induced mice for a period of 30 days.  From the result it was concluded that the extract has as a potent antitumor activity and that is comparable to 5-fluorouracil.</p><p> </p>

scholarly journals The Anti-Tumoral Effects of Wolfberry (Lycium barbarum) on Experimentally Induced Ehrlich Ascites Carcinoma in Mice

Proceedings ◽  
2019 ◽  
Vol 40 (1) ◽  
pp. 38
Author(s):  
Uçar ◽  
Ülger ◽  
AL ◽  
Nisari ◽  
Karatoprak
Keyword(s):  
Histopathological Examination ◽  
Apoptotic Cell ◽  
Ehrlich Ascites Carcinoma ◽  
Lycium Barbarum ◽  
In Vitro Techniques ◽  
Cell Percentage ◽  
Ehrlich Ascites ◽  
Eat Cells

Wolfberry (Lycium barbarum) shows strengthen immune system, antioxidant and anticancerogenic effect. In this research, the effects of Wolfberry's extract fractions, cultivated in Kayseri, investigated on Ehrlich ascites tumor (EAT) using in vivo and in vitro techniques. For in vivo study, 200 mg/kg fractions of Wolfberry extract (above and below 50 kDa) were injected ip to EAT injected Balb/C mice. EAT cells were also cultured in the presence of Wolfberry's extract fractions (1500, 2000 µg/ml) to examine cell vitality and apoptosis using the Muse Cell Analyzer. Histopathological examination of intra-abdominal organs showed that there were decrease in the EAT cells adherence in the Wolfberry applied tissue groups when compared to the control. According to in vitro results, the both extract fractions (above and below 50 kDa) increased apoptosis in cancer cells. However, total apoptotic cell percentage was higher and statistically significant in groups above 50 kDa (1500, 2000 mg/ml) (p < 0.05). Previous literature and the results of the present study reveal that the consumption of wolfberry—which is also produced in Turkey—might be effective in preventing the formation of cancer and the deceleration of its progress.

scholarly journals In vitro and in vivo antileishmanial efficacy of a combination therapy of diminazene and artesunate against Leishmania donovani in BALB/c mice

2011 ◽  
Vol 53 (3) ◽  
pp. 129-132 ◽  
Author(s):  
Joshua Muli Mutiso ◽  
John Chege Macharia ◽  
Mustafa Barasa ◽  
Evans Taracha ◽  
Alain J. Bourdichon ◽  
...  
Keyword(s):  
Leishmania Donovani ◽  
Combined Therapy ◽  
Parasite Burden ◽  
Mice Model ◽  
In Vivo Evaluation ◽  
Reference Drug ◽  
Drug Treatments ◽  
Potential Use

The in vitro and in vivo activity of diminazene (Dim), artesunate (Art) and combination of Dim and Art (Dim-Art) against Leishmania donovani was compared to reference drug; amphotericin B. IC50 of Dim-Art was found to be 2.28 ± 0.24 µg/mL while those of Dim and Art were 9.16 ± 0.3 µg/mL and 4.64 ± 0.48 µg/mL respectively. The IC50 for Amphot B was 0.16 ± 0.32 µg/mL against stationary-phase promastigotes. In vivo evaluation in the L. donovani BALB/c mice model indicated that treatments with the combined drug therapy at doses of 12.5 mg/kg for 28 consecutive days significantly (p < 0.001) reduced parasite burden in the spleen as compared to the single drug treatments given at the same dosages. Although parasite burden was slightly lower (p < 0.05) in the Amphot B group than in the Dim-Art treatment group, the present study demonstrates the positive advantage and the potential use of the combined therapy of Dim-Art over the constituent drugs, Dim or Art when used alone. Further evaluation is recommended to determine the most efficacious combination ratio of the two compounds.

scholarly journals In vitro and in vivo evaluation of anisomycin against Ehrlich ascites carcinoma

2013 ◽  
Vol 29 (6) ◽  
pp. 2227-2236 ◽  
Author(s):  
PENGTAO YOU ◽  
FEIYUE XING ◽  
JIE HUO ◽  
BAOYU WANG ◽  
JINGFANG DI ◽  
...  
Keyword(s):  
Ehrlich Ascites Carcinoma ◽  
In Vivo Evaluation ◽  
Ehrlich Ascites

Evaluation of Cisplatin Combined with Ondansetron in Ehrlich Ascites Carcinoma in Vitro and in Vivo

2000 ◽  
Vol 86 (2) ◽  
pp. 153-156 ◽  
Author(s):  
Osama Ahmed Badary ◽  
Sahar Moustafa Sharaby ◽  
Sanaa Abd El-Baky Kenawy ◽  
Ezz El-Deen El-Denshary ◽  
Farid Mohamed Ahmed Hamada
Keyword(s):  
Antitumor Activity ◽  
Ehrlich Ascites Carcinoma ◽  
Host Tissue ◽  
Nausea And Vomiting ◽  
Single Treatment ◽  
Blood Cell Count ◽  
Ehrlich Ascites ◽  
Eac Cells

Aims and background Nausea and vomiting occur in the majority of patients receiving cisplatin (CDDP) chemotherapy. Ondansetron, a new 5-HT3 receptor antagonist, has been used effectively to control CDDP-induced nausea and vomiting. This study examined the potential of ondansetron to interfere with CDDP antitumor activity and toxicity in Ehrlich ascites carcinoma (EAC). Methods The influence of ondansetron on CDDP cytotoxicity was evaluated using EAC cells in culture. In addition, the influence of ondansetron pretreatment on CDDP-induced antitumor activity and host tissue toxicity was studied in EAC-bearing mice. Results Ondansetron (0.25 μM) enhanced CDDP (0–32 μM) cytotoxicity against EAC cells in vitro. In EAC-bearing mice ondansetron (0.2 mg/kg, ip) administered 1 h before CDDP (7 mg/kg, ip) did not modify the antitumor activity of CDDP. CDDP (7 mg/kg, ip) single treatment induced significant increases in blood urea nitrogen (2-fold) and serum creatinine (2.5-fold) and significant decreases in hematocrit (25%) and white blood cell count (39%) compared to saline treatment. Mice receiving ondansetron 1 h before CDDP showed no significant enhancement of CDDP-induced nephrotoxicity or myelosuppression compared to those pretreated with saline receiving the same dose of CDDP. Conclusions This study suggests that the use of ondansetron to control CDDP-induced nausea and vomiting does not affect CDDP antitumor efficacy.

scholarly journals Ethanolic Extract of Senna velutina Roots: Chemical Composition, In Vitro and In Vivo Antitumor Effects, and B16F10-Nex2 Melanoma Cell Death Mechanisms

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
David Tsuyoshi Hiramatsu Castro ◽  
Jaqueline Ferreira Campos ◽  
Marcio José Damião ◽  
Heron Fernandes Vieira Torquato ◽  
Edgar Julian Paredes-Gamero ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Chemical Composition ◽  
Caspase 3 ◽  
Tumor Volume ◽  
Apoptotic Cell ◽  
Ethanolic Extract ◽  
Antitumor Effects ◽  
Cycle Arrest

Cutaneous melanoma is among the most aggressive types of cancer, and its rate of occurrence increases every year. Current pharmacological treatments for melanoma are not completely effective, requiring the identification of new drugs. As an alternative, plant-derived natural compounds are described as promising sources of new anticancer drugs. In this context, the objectives of this study were to identify the chemical composition of the ethanolic extract of Senna velutina roots (ESVR), to assess its in vitro and in vivo antitumor effects on melanoma cells, and to characterize its mechanisms of action. For these purposes, the chemical constituents were identified by liquid chromatography coupled to high-resolution mass spectrometry. The in vitro activity of the extract was assessed in the B16F10-Nex2 melanoma cell line using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and based on the apoptotic cell count; DNA fragmentation; necrostatin-1 inhibition; intracellular calcium, pan-caspase, and caspase-3 activation; reactive oxygen species (ROS) levels; and cell cycle arrest. The in vivo activity of the extract was assessed in models of tumor volume progression and pulmonary nodule formation in C57Bl/6 mice. The chemical composition results showed that ESVR contains flavonoid derivatives of the catechin, anthraquinone, and piceatannol groups. The extract reduced B16F10-Nex2 cell viability and promoted apoptotic cell death as well as caspase-3 activation, with increased intracellular calcium and ROS levels as well as cell cycle arrest at the sub-G0/G1 phase. In vivo, the tumor volume progression and pulmonary metastasis of ESVR-treated mice decreased over 50%. Combined, these results show that ESVR had in vitro and in vivo antitumor effects, predominantly by apoptosis, thus demonstrating its potential as a therapeutic agent in the treatment of melanoma and other types of cancer.

Chloroform Fraction of Methanolic Extract of Seeds of Annona muricata Induce S Phase Arrest and ROS Dependent Caspase Activated Mitochondria Mediated Apoptosis in Triple Negative Breast Cancer

2020 ◽  
Vol 20 ◽  
Author(s):  
Ajith J. George ◽  
Bibu J. Kariyil ◽  
Usha P.T. Ayyappan ◽  
Anu Gopalakrishnan
Keyword(s):  
Cell Cycle ◽  
Cell Lines ◽  
Triple Negative ◽  
S Phase ◽  
Chloroform Fraction ◽  
Annona Muricata ◽  
In Vivo Evaluation ◽  
Annonaceous Acetogenins

Background: Triple negative breast cancers (TNBCs) are having high morbidity and shorter survival rate in the population. These types of cancers are having high aggressiveness, lymphatic invasion and absence of receptors. The treatment options for these types of cancers are also scarce. Several studies have been conducted to investigate the effectiveness of seeds of Annona muricata for its anti cancer activities in various cancer cell lines such as lung A549, breast MCF7, colon HT-29, oral KB and human hepatoma cell lines. But works related to its anticancer effect and mechanism of action in TNBCs has not been elucidated. Objective: The present study was undertaken to evaluate the in vitro, in vivo and in silico anticancer potential of chloroform fraction of methanolic extract of seeds of Annona muricata (CMAM) against TNBC along with elucidation of its mechanistic pathway. Methods: In vitro cytotoxicity- and antiproliferative- studies in three triple negative breast cancer cell lines were conducted using MTT and SRB assays respectively. The mechanism through which CMAM exerts its pharmacological effect was elucidated in vitro employing cell morphological assessment studies using acridine orange/ ethidium bromide (AO/EB), intra cellular reactive oxygen species assay, DNA fragmentation assay, agarose gel electrophoresis, terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay, cell cycle analysis, annexin binding assay and caspase activated mitochondria mediated apoptotic assays using western blot. In vivo evaluation in 4T1 induced murine mammary tumour model was also conducted. Phytoconstituents in CMAM was analysed using liquid chromatography mass spectroscopy. In silico binding studies with various annonaceous acetogenins against BCL-2 and cyclin E were performed. Results: Cytotoxicity studies in MDA-MD-231, 4TI and BT-549 revealed the IC50 value of CMAM to be 2.5±0.14, 4.8±0.3 and 4.5±0.16 µg/mL respectively. Anti proliferative studies in 4T1, MDA-MB-231 and BT-549 revealed the GI50 values to be 0.128+0.03, 18.03+0.20, 0.95+0.04 µg/mL respectively. CMAM exhibited its cytotoxicity through the lysis of cell membrane, ROS dependent caspase activated mitochondria mediated apoptosis, and arresting the S phase of the cell cycle. In vivo evaluation also supported the tumoricidal property of CMAM as evidenced by reduction in tumour volume and serum biomarkers. Histopathologically there was a marked reduction in cellularity, nuclear chromatin condensation and a few normal cells in group treated with CMAM at a dose of 31mg/Kg. Phytoconstituent evaluation has revealed the presence of annonaceous acetogenins in CMAM. Among the various annonaceous acetogenins, muricatacin alone showed lipophilicity and binding affinity towards BCL-2 and cyclin E1. Conclusion: The current study shows the effectiveness of CMAM against TNBC both in vitro and in vivo. This anticancerous effect of CMAM could be by virtue of its ROS dependent caspase activated mitochondria mediated apoptosis and the S-phase arrest of the cell cycle in the TNBCs. Our results indicate that the presence of annonaceous acetogenins, especially muricatacin, could be contributing to this anticanceros effect of CMAM. Thus muricatacin could be a potential candidate for the targeted therapy of TNBCs.

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