scholarly journals Cytotoxic, Antitumor and Toxicological Profile of Passiflora alata Leaf Extract

Molecules ◽  
2020 ◽  
Vol 25 (20) ◽  
pp. 4814
Author(s):  
Ricardo G. Amaral ◽  
Silvana V. F. Gomes ◽  
Luciana N. Andrade ◽  
Sara A. dos Santos ◽  
Patrícia Severino ◽  
...  

Passiflora alata or passion fruit is a native flowering plant from Amazon, geographically spread from Peru to Brazil. The plant has long been used in folks medicine for its pharmacological properties and is included in the Brazilian Pharmacopoeia since 1929. The aim of this study was to evaluate the potential cytotoxic and antitumor activities of Passiflora alata leaf extract (PaLE) in S180-tumor bearing mice. The percentage of cell proliferation inhibition (% CPI) and IC50 in relation to 4 tumor cell lines were determined in PC3, K-562, HepG2 and S180 cell lines using the MTT assay. PaLE showed a CPI > 75% and greater potency (IC50 < 30 µg/mL) against PC3 and S180 cell lines. PaLE showed antitumor activity in treatments intraperitoneally (36.75% and 44.99% at doses of 100 and 150 mg/kg/day, respectively). Toxicological changes were shown in the reduced body mass associated with reduced food consumption, increased spleen mass associated with histopathological increase in the white pulp of the spleen and increased number of total leukocytes with changes in the percentage relationship between lymphocytes and neutrophils. Our outcomes corroborate the conclusion that PaLE has antitumor activity in vitro and in vivo with low toxicity.

Molecules ◽  
2021 ◽  
Vol 26 (7) ◽  
pp. 1838
Author(s):  
Naglaa M. Ahmed ◽  
Mahmoud M. Youns ◽  
Moustafa K. Soltan ◽  
Ahmed M. Said

Scaffolds hybridization is a well-known drug design strategy for antitumor agents. Herein, series of novel indolyl-pyrimidine hybrids were synthesized and evaluated in vitro and in vivo for their antitumor activity. The in vitro antiproliferative activity of all compounds was obtained against MCF-7, HepG2, and HCT-116 cancer cell lines, as well as against WI38 normal cells using the resazurin assay. Compounds 1–4 showed broad spectrum cytotoxic activity against all these cancer cell lines compared to normal cells. Compound 4g showed potent antiproliferative activity against these cell lines (IC50 = 5.1, 5.02, and 6.6 μM, respectively) comparable to the standard treatment (5-FU and erlotinib). In addition, the most promising group of compounds was further evaluated for their in vivo antitumor efficacy against EAC tumor bearing mice. Notably, compound 4g showed the most potent in vivo antitumor activity. The most active compounds were evaluated for their EGFR inhibitory (range 53–79 %) activity. Compound 4g was found to be the most active compound against EGFR (IC50 = 0.25 µM) showing equipotency as the reference treatment (erlotinib). Molecular modeling study was performed on compound 4g revealed a proper binding of this compound inside the EGFR active site comparable to erlotinib. The data suggest that compound 4g could be used as a potential anticancer agent.


2021 ◽  
Author(s):  
Andjela Franich ◽  
◽  
Milica Dimitrijević Stojanović ◽  
Snežana Rajković ◽  
Marina Jovanović ◽  
...  

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.


Cells ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 1592
Author(s):  
Surendra R. Punganuru ◽  
Viswanath Arutla ◽  
Wei Zhao ◽  
Mehrdad Rajaei ◽  
Hemantkumar Deokar ◽  
...  

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.


Molecules ◽  
2014 ◽  
Vol 19 (7) ◽  
pp. 8740-8751 ◽  
Author(s):  
Xiao-Kun Yang ◽  
Ming-Yuan Xu ◽  
Gui-Sen Xu ◽  
Yu-Lan Zhang ◽  
Zhao-Xia Xu

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5306-5306
Author(s):  
Lei Fan ◽  
Chao Wang ◽  
Zhiqiang Wang ◽  
Xian Zhang ◽  
Lei Cao ◽  
...  

Introduction : PI3Kδ, one of the class I PI3Ks, is found expressed primarily in leukocytes and plays an essential role in B-cell development and function. Here, we comprehensively evaluated the in vitro and in vivo antitumor activity and the underlying mechanism of SHC014748M, an oral selective inhibitor of PI3Kδ under Phase I clinical evaluation. Methods : Biochemical and cell-based assays were used to measure compound potency and selectivity in lymphoma cell lines as well as primary CLL cells, and PI3K/AKT pathway was measured by Western blot assay, Alphalisa and Elisa. Xenograft model was carried out to validate in-vivo antitumor potency of the compound. Besides, chemokines and cytokines derived from blood samples of patients were also detected. Results: SHC014748M was 125- to 306-fold more selective for PI3Kδ inhibition relative to other class I PI3K enzymes and showed in vitro activity in most of 23 B lymphoma cell lines. We identified that SHC014748M treatment resulted in a 3.1- to 5.5-fold increase in annexin V/7-ADD staining, indicating a significant apoptosis induction. SHC014748M inhibited phosphorylation of AKT, targets downstream of PI3Kδ, in lymphoma cells. Among the 15 primary CLL cells, the 50% inhibitory concentration (IC50) of SHC014748M varies from 850 nM to 37040 nM respectively and expression of phosphorylation AKT decreased to the normal levels in the presence of SHC014748M or positive control, Idelalisib. In-vivo study revealed that SHC014748M significantly reduced lymphoma cell growth in the treatment group compared with control mice. CCL4, CCL17, CCL22 and CXCL13 derived from patients decreased sharply after SHC014748M treatment. Conclusion: According to the results, SHC014748M appeared to be a novel promising compound in the treatment of B cell lymphomas and CLL. Disclosures Wang: Nanjing Sanhome Pharmaceutical Co., Ltd.: Employment. Wang:Nanjing Sanhome Pharmaceutical Co., Ltd.: Employment. Zhang:Nanjing Sanhome Pharmaceutical Co., Ltd.: Employment.


2018 ◽  
Vol 2 (23) ◽  
pp. 3516-3525 ◽  
Author(s):  
Kyle Runckel ◽  
Matthew J. Barth ◽  
Cory Mavis ◽  
Juan J. Gu ◽  
Francisco J. Hernandez-Ilizaliturri

Abstract Clinical observations suggest the existence of shared resistance pathways between rituximab and chemotherapy agents. To explore the mechanisms of rituximab resistance, our group created rituximab-resistant cell lines (RRCLs), which display altered expression of several inhibitor of apoptosis (IAP) family proteins. Here, we provide evidence to support pharmacologically targeting IAPs in lymphoma with LCL-161, a small molecule mimetic of the second mitochondria-derived activator of caspases (SMAC). The antitumor effect of LCL-161 was determined using luminescent adenosine triphosphate assays, flow cytometry, SCID mouse xenografts, and ex vivo patient biopsy sample studies. In vitro exposure to LCL-161 also resulted in a dose-dependent decrease in IAP levels, along with synergistic enhancement of the antitumor effect of cytotoxic chemotherapy, in rituximab-sensitive cell lines and RRCLs. In addition, LCL-161 increased the cytotoxic effect of the proteasome inhibitor carfilzomib in ex vivo lymphoma patient samples. The combination of LCL-161 with the chemotherapy regimen rituximab, gemcitabine, and vinorelbine (RGV) improved in vivo survival compared with RGV alone in severe combined immunodeficient mice implanted with RRCLs but not in animals implanted with rituximab-sensitive cell lines. In summary, LCL-161 exhibits synergistic antitumor activity in both in vitro and in vivo models of resistant lymphoma. Our data support further preclinical investigation of LCL-161 as a novel antilymphoma agent.


2020 ◽  
Vol 4 (17) ◽  
pp. 4124-4135 ◽  
Author(s):  
Filippo Spriano ◽  
Eugenio Gaudio ◽  
Luciano Cascione ◽  
Chiara Tarantelli ◽  
Federica Melle ◽  
...  

Abstract Bromodomain and extra-terminal domain (BET) proteins, cyclic adenosine monophosphate response element-binding protein (CBP), and the E1A-binding protein of p300 (EP300) are important players in histone acetylation. Preclinical evidence supports the notion that small molecules targeting these proteins individually or in combination can elicit antitumor activity. Here, we characterize the antitumor activity of the pan BET/CBP/EP300 inhibitor NEO2734 and provide insights into its mechanism of action through bromodomain-binding assays, in vitro and in vivo treatments of cancer cell lines, immunoblotting, and transcriptome analyses. In a panel of 60 models derived from different tumor types, NEO2734 exhibited antiproliferative activity in multiple cell lines, with the most potent activity observed in hematologic and prostate cancers. Focusing on lymphoma cell lines, NEO2374 exhibited a pattern of response and transcriptional changes similar to lymphoma cells exposed to either BET or CBP/EP300 inhibitors alone. However, NEO2734 was more potent than single-agent BET or CBP/EP300 inhibitors alone. In conclusion, NEO2734 is a novel antitumor compound that shows preferential activity in lymphomas, leukemias, and prostate cancers.


1988 ◽  
Vol 66 (1) ◽  
pp. 187-190 ◽  
Author(s):  
Hans H. Baer ◽  
Lisa Siemsen

Methyl 3-amino-2,3,6-trideoxy-2-fluoro-β-L-galactopyranoside was hydrolyzed to the free sugar, (S)-2-fluorodaunosamine hydrochloride, which was converted into the α,β-1,4-di-O-acetyl-N-trifluoroacetyl derivative and thence into the corresponding glycosyl bromide. The latter was condensed with daunomycinone, and the product was deprotected to give the title compound. The fluoroanthracycline displayed significant cytotoxicity against a number of tumor cell lines in vitro. Antitumor activity against L1210 murine leukemia in vivo was lower than that of the parent daunorubicin, but toxicity appeared to be reduced.


Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1023
Author(s):  
Rodica Mărgăoan ◽  
Erkan Topal ◽  
Ralitsa Balkanska ◽  
Banu Yücel ◽  
Titanilla Oravecz ◽  
...  

Background: vegetative diversity is based on different climate and geographical origins. In terms of beekeeping, herbal diversity is strongly correlated to the production of a wide variety of honey. Therefore, based on the existing plant diversity in each country, multiple honey varieties are produced with different health characteristics. While beekeeping potential and consumption preferences are reflected in products’ variety, this leads to an increase in the region’s economy and extensive export. In the last years, monofloral honey has gained interest from consumers and especially in the medicinal field due to the presence of phytochemicals which are directly linked to health benefits, wound healing, antioxidant, anticancer and anti-inflammatory activities. Scope and approach: this review aims to highlight the physicochemical properties, mineral profiles and antioxidant activities of selected monofloral honeys based on their botanical and geographical origin. Moreover, this review focuses on the intercorrelation between monofloral honey’s antioxidant compounds and in vitro and in vivo activities, focusing on the apoptosis and cell proliferation inhibition in various cell lines, with a final usage of honey as a potential therapeutic product in the fight towards reducing tumor growth. Key findings and conclusions: multiple studies have demonstrated that monofloral honeys have different physicochemical structures and bioactive compounds. Useful chemical markers to distinguish between monofloral honeys were evidenced, such as: 2-methoxybenzoic acid and trimethoxybenzoic acid are distinctive to Manuka honey while 4-methoxyphenylacetic acid is characteristic to Kanuka honey. Furthermore, resveratrol, epigallocatechin and pinostrobin are markers distinct to Sage honey, whereas carvacrol and thymol are found in Ziziphus honey. Due to their polyphenolic profile, monofloral honeys have significant antioxidant activity, as well as antidiabetic, antimicrobial and anticancer activities. It was demonstrated that Pine honey decreased the MDA and TBARS levels in liver, kidney, heart and brain tissues, whereas Malicia honey reduced the low-density lipoprotein level. Consumption of Clover, Acacia and Gelam honeys reduced the weight and adiposity, as well as trygliceride levels. Furthermore, the antiproliferative effect of chrysin, a natural flavone in Acacia honey, was demonstrated in human (A375) and murine (B16-F1) melanoma cell lines, whereas caffeic acid, a phenolic compound found in Kelulut honey, proves to be significant candidate in the chemoprevention of colon cancer. Based on these features, the use of hiney in the medicinal field (apitherapy), and the widespread usage of natural product consumption, is gaining interest by each year.


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