Encapsulation of Variabilin in Stearic Acid Solid Lipid Nanoparticles Enhances Its Anticancer Activity in Vitro

The use of natural products as chemotherapeutic agents is well established; however, many of these are associated with undesirable side effects, including high toxicity and instability. Furthermore, the development of drug resistant cancers makes the search for new anticancer lead compounds a priority. In this study, the extraction of an Ircinia sp. sponge resulted in the isolation of an inseparable mixture of (7E,12E,20Z)-variabilin (1) and (7E,12Z,20Z)-variabilin (2) and structural assignment was established using standard 1D and 2D NMR experiments. The cytotoxic activity of the compound against three solid tumour cell lines displayed moderate anti-cancer activity through apoptosis, together with a general lack of selectivity among the cancer cell lines studied. Structural assignment and cytotoxic evaluation of variabilin was complicated and further aggravated by its inherent instability. Variabilin was therefore incorporated into solid lipid nanoparticles (SLNs) and the stability and cytotoxic activity evaluated. Encapsulation of variabilin into SLNs led to a marked improvement in stability of the natural product coupled with enhanced cytotoxic activity, particularly against the prostate (PC-3) cancer cell line, with IC50 values of 87.74 μM vs. 8.94 μM for the variabilin alone and Var-SLN, respectively. Both variabilin and Var-SLN revealed comparable activity to Ceramide against the MCF-7 breast cancer cell line, revealing IC50 values of 34.8, 38.1 and 33.6 μM for variabilin, Var-SLN and Ceramide, respectively. These samples revealed no activity (>100 μM for all) against HT-29 (colon) cell lines and MCF-12 (normal breast) cell lines. Var-SLNs induced 47, 48 and 59% of apoptosis in HT-29, MCF-7 and PC-3 cells, respectively, while variabilin alone revealed 38, 29 and 29% apoptotic cells for HT-29, MCF-7 and PC-3 cell lines, respectively. The encapsulation of natural products into SLNs may provide a promising approach to overcome some of the issues hindering the development of new anticancer drugs from natural products.

Download Full-text

Cytotoxic Sterols from Philippine Mushrooms

Asian Journal of Chemistry ◽

10.14233/ajchem.2020.22591 ◽

2020 ◽

Vol 32 (5) ◽

pp. 1197-1202

Author(s):

Consolacion Y. Ragasa ◽

Glenn G. Oyong ◽

Maria Carmen S. Tan ◽

Mariquit M. De Los Reyes ◽

Maria Ellenita G. De Castro

Keyword(s):

Cell Lines ◽

Cancer Cell ◽

Human Cancer ◽

Dermal Fibroblast ◽

Cancer Cell Lines ◽

Cytotoxic Activities ◽

Cell Viability Assay ◽

Ic50 Values ◽

Ht 29 ◽

Mcf 7

Ergosterol peroxide (1) and ergosterol (2) were commonly isolated as the major compounds of Philippine mushrooms. Sterols 1 and 2 from the dichloromethane extract of Geastrum triplex and Termitomyces clypeatus, respectively, were evaluated for their cytotoxic activities against four human cancer cell lines, viz., breast cancer (MCF-7), colon cancer (HT-29), leukemia (THP-1), and small lung cell carcinoma (H69PR), and a human normal cell line, human dermal fibroblast-neonatal (HDFn), using the PrestoBlue® cell viability assay. Compounds 1 and 2 exhibited the strongest activities against HT-29 with IC50 values of 1.79 and 2.98 μg/mL, respectively, while Zeocin gave an IC50 of 4.89 μg/mL. These compounds also exhibited strong antiproliferative effects against MCF-7 with IC50 values of 4.13 for 1 and 4.20 μg/mL for compound 2, comparable to Zeocin with IC50 = 3.68 μg/mL. Only moderate cytotoxicity resulted when compounds 1 and 2 were tested against H69PR with IC50 values of 7.78 and 6.83 μg/mL, respectively, while Zeocin exhibited an IC50 of 9.81 μg/mL. Furthermore, compounds 1 and 2 showed no effects against THP-1 (IC50 > 100 μg/mL), while Zeocin showed an IC50 of 4.73 μg/mL. Although compounds 1 and 2 have been reported to exhibit different bioactivities in previous studies, the cancer cell lines tested and/or the polarities of the solvents for extraction varied. Therefore, comparisons of the cytotoxic activities of compounds 1 and 2 with earlier studies could not be made extensively.

Download Full-text

NEW QUINAZOLINONE DERIVATIVES: SYTHESIS AND IN VITRO CYTOTOXIC ACTIVITY

Vietnam Journal of Science and Technology ◽

10.15625/2525-2518/58/1/14391 ◽

2020 ◽

Vol 58 (1) ◽

pp. 12

Author(s):

Tran Khac Vu

Keyword(s):

Cytotoxic Activity ◽

Cell Lines ◽

Cancer Cell ◽

Cytotoxic Effect ◽

Cancer Cell Lines ◽

Ic50 Values ◽

Quinazolinone Derivatives ◽

Bioassay Result ◽

Mcf 7

The paper presents a simple synthesis of new quinazolinone derivatives 13a-i. Synthesized derivatives were tested for their cytotoxic effect against three cancer cell lines including SKLU-1, MCF-7 and HepG-2. The bioassay result showed that only compound 13e exhibited significant cytotoxic effect against cancer cell lines tested with IC50 values of 9.48, 20.39 and 18.04 µg/ mL, respectively.

Download Full-text

Imidazole and carbazole derivatives as potential anticancer agents: molecular docking studies and cytotoxic activity evaluation

Bulletin of the Chemical Society of Ethiopia ◽

10.4314/bcse.v34i2.14 ◽

2020 ◽

Vol 34 (2) ◽

pp. 377-384

Author(s):

B. Taheri ◽

M. Taghavi ◽

M. Zarei ◽

N. Chamkouri ◽

A. Mojaddami

Keyword(s):

Molecular Docking ◽

Cytotoxic Activity ◽

Cell Lines ◽

Biological Activities ◽

Docking Studies ◽

Carbazole Derivatives ◽

Ic50 Values ◽

Docking Energy ◽

Ht 29 ◽

Mcf 7

Carbazoles and imidazole represent two important classes of heterocycles which exhibit diverse biological activities such as antitumor properties. In this study, imidazole (C1-C3) and carbazole (C4 and C5) derivatives were evaluated for their cytotoxic activity against three human cancer cell lines namely, MCF7 (human breast cancer), HT29 (human colon cancer), and HeLa (human cervical cancer). Carbazole derivatives (C4 and C5) with IC50 < 10 µM showed greater cytotoxic effect than imidazole derivatives (C1-C3). Furthermore, all compounds exhibited better anticancer activity against MCF-7 than other two cell lines (HT-29, HeLa) and compound C4 was the most potent compound with the IC50 values of 2.5, 5.4 and 4.0 µM, against MCF-7, Hela and HT-29 cell lines, respectively. Physicochemical properties of compounds were calculated and their correlation with the IC50 values on MCF-7 cell line investigated. Surface area and polarizability of compounds showed good correlation by R2 = 0.8396 and R2 = 0.834, respectively. Docking studies of these compounds were also performed on the DNA as proposed target to comprehend their binding interactions and binding energies. The docking energy of compounds ranged from - 11.32 to -13.48 kcal/mol. Compound C3 with energy of -13.48 kcal/mol had the highest docking energy. Docking results indicated that these compounds (C1-C5) had strong affinity in binding to the DNA. KEY WORDS: Imidazole, Carbazole, Molecular docking, Cancer, MTT assay Bull. Chem. Soc. Ethiop. 2020, 34(2), 377-384 DOI: https://dx.doi.org/10.4314/bcse.v34i2.14

Download Full-text

Damarane-type Saponins from Gynostemma Longipes and their Cytotoxic Activity

Natural Product Communications ◽

10.1177/1934578x1501000808 ◽

2015 ◽

Vol 10 (8) ◽

pp. 1934578X1501000

Author(s):

Pham Tuan Anh ◽

Pham Thanh Ky ◽

Nguyen Thi Cuc ◽

Nguyen Xuan Nhiem ◽

Pham Hai Yen ◽

...

Keyword(s):

Cytotoxic Activity ◽

Cell Lines ◽

Cancer Cell ◽

Human Cancer ◽

2D Nmr ◽

Moderate Activity ◽

Human Cancer Cell ◽

Human Cancer Cell Lines ◽

Ht 29 ◽

Mcf 7

Two new damarane- type saponins, named gylongiposides II-III (1 and 2), along with one known compound, (23 S)-3β,20ζ,21ζ-trihydroxy-19-oxo-21,23-epoxydammar-24-ene 3- O-α-L-rhamnopyranosyl-(1→2)-[β-D-xylopyranosyl-(1→3)]-α-L-arabinopyranoside, were isolated from the leaves of Gynostemma longipes C.Y.Wu. Their structures were determined by 1D- and 2D-NMR and HR-ESI-MS spectra. Compounds 1–3 exhibited moderate activity against four human cancer cell lines, A-549, HT-29, OVCAR, and MCF-7, with IC50 values ranging from 9.8 ± 2.1 to 49.6 ± 2.6 μM.

Download Full-text

Isolation, Characterization, Complete Structural Assignment, and Anticancer Activities of the Methoxylated Flavonoids from Rhamnus disperma Roots

Molecules ◽

10.3390/molecules26195827 ◽

2021 ◽

Vol 26 (19) ◽

pp. 5827

Author(s):

Hamdoon A. Mohammed ◽

Mohammed F. Abd El-Wahab ◽

Usama Shaheen ◽

Abd El-Salam I. Mohammed ◽

Ashraf N. Abdalla ◽

...

Keyword(s):

Cytotoxic Activity ◽

Cell Lines ◽

Cancer Cell ◽

Cancer Cell Lines ◽

Structure Characterization ◽

Lung Fibroblasts ◽

Flavonoid Glycosides ◽

Isolation And Purification ◽

Ic50 Values ◽

Mcf 7

Different chromatographic methods including reversed-phase HPLC led to the isolation and purification of three O-methylated flavonoids; 5,4’-dihydroxy-3,6,7-tri-O-methyl flavone (penduletin) (1), 5,3’-dihydroxy-3,6,7,4’,5’-penta-O-methyl flavone (2), and 5-hydroxy-3,6,7,3’,4’,5’-hexa-O-methyl flavone (3) from Rhamnus disperma roots. Additionlly, four flavonoid glycosides; kampferol 7-O-α-L-rhamnopyranoside (4), isorhamnetin-3-O-β-D-glucopyranoside (5), quercetin 7-O-α-L-rhamnopyranoside (6), and kampferol 3, 7-di-O-α-L-rhamnopyranoside (7) along with benzyl-O-β-D-glucopyranoside (8) were successfully isolated. Complete structure characterization of these compounds was assigned based on NMR spectroscopic data, MS analyses, and comparison with the literature. The O-methyl protons and carbons of the three O-methylated flavonoids (1–3) were unambiguously assigned based on 2D NMR data. The occurrence of compounds 1, 4, 5, and 8 in Rhamnus disperma is was reported here for the first time. Compound 3 was acetylated at 5-OH position to give 5-O-acetyl-3,6,7,3’,4’,5’-hexa-O-methyl flavone (9). Compound 1 exhibited the highest cytotoxic activity against MCF 7, A2780, and HT29 cancer cell lines with IC50 values at 2.17 µM, 0.53 µM, and 2.16 µM, respectively, and was 2–9 folds more selective against tested cancer cell lines compared to the normal human fetal lung fibroblasts (MRC5). It also doubled MCF 7 apoptotic populations and caused G1 cell cycle arrest. The acetylated compound 9 exhibited cytotoxic activity against MCF 7 and HT29 cancer cell lines with IC50 values at 2.19 µM and 3.18 µM, respectively, and was 6–8 folds more cytotoxic to tested cancer cell lines compared to the MRC5 cells.

Download Full-text

In Vitro Anti-proliferative Properties of Flavonoids Isolated from Artocarpus heterophyllus on Cancer Cell Lines

The Natural Products Journal ◽

10.2174/2210315510999201026230628 ◽

2020 ◽

Vol 10 ◽

Author(s):

Abdi Wira Septama ◽

Noor Azlina Abu Bakar ◽

Nik Nurul Najihah Nik Mat Daud

Keyword(s):

Cytotoxic Activity ◽

Cancer Cells ◽

Cell Lines ◽

Cancer Cell ◽

Morphological Changes ◽

Cancer Cell Lines ◽

Artocarpus Heterophyllus ◽

Flavonoid Compounds ◽

Ht 29 ◽

Mcf 7

Abstract:: Artocarpus heterophyllus, has been used as a folk medicine. This plant contained wide range of flavonoid compounds and possessed several pharmacological properties including anticancer. Chemotherapeutic agent is major option for cancer treatment. However, it may lead to tumor relapse. Therefore, it needs to discover alternative to reduce this limitation using natural products. Objective:: This study was aimed to determine anti-proliferative activities of isolated compounds against cancer cell lines. The morphological changes of cancer cell lines after treatment with the compounds was also evaluated. Methods:: The flavonoid compounds were determined for their cytotoxic activity against leukaemia HL-60 (CCL-240), colorectal adenocarcinoma HT-29 (HTB-38), breast adenocarcinoma cancer MCF-7 (HTB-22), and non-small lung cancer H460 (HTB-177) cell lines using MTT assay. Hoechst 33342/PI staining assay was used to evaluated the morphological changes, and observed using fluorescent microscope. Results:: It showed that amongst compound, artocarpin consistently exhibited strong cytotoxic activity against H460, HT-29, MCF-7, and HL-60 cancer cell lines with IC50 values of 5.07, 5.56, 12.53, and 19.94 μg/mL, respectively. The activity was comparable to the cisplatin as a positive control. Morphological observations showed the most typical apoptotic morphology of cancer cells upon treatment with artocarpin and the least typical of apoptotic structure with other compounds. Conclusion:: It can be suggested that A. heterophyllus bioactive compound modulates apoptosis by the presence of its distinctive, typical forms of morphological changes in treating cancer cells. Thus, artocarpin compound may provide high potential therapeutic use in chemotherapeutic strategies.

Download Full-text

Cytotoxic Activity of Ethanolic Extract of Aloe saudiarabica and Aloe shadensis against Three Human Cancer Cell Line

Journal of Pharmaceutical Research International ◽

10.9734/jpri/2021/v33i45b32790 ◽

2021 ◽

pp. 138-146

Author(s):

Awad A Algarni

Keyword(s):

Cytotoxic Activity ◽

Cell Line ◽

Cell Lines ◽

Cancer Cell ◽

Human Cancer ◽

A549 Cells ◽

Cancer Cell Line ◽

Human Cancer Cell ◽

Main Compound ◽

Mcf 7

Aloe saudiarabica and Aloe shadensis are a rare species of the genus Aloe found only in Saudi Arabia. The cytotoxic activity of both plants were evaluated in the current study using three different human cancer cell line, lung carcinoma (A-549), breast adenocarcinoma (MCF-7) and liver cancer (HepG2), assessed by WST-1 cell viability assays. The results indicate that the Aloe saudiarabica and Aloe shadensis showed weak cytotoxic effects against all three tested cancer cell lines, with an IC50 value of >300 μg/ml. In addition, HepG2 cells were more sensitive to Aloe saudiarabica treatment than MCF-7 and A549 cells, while MCF-7 cells were more sensitive to Aloe shadensis treatment than HepG2 and A549 cells. This study also identified the characteristic chemical constituents of the two plants using gas chromatography-mass spectrometry technique and the result indicated that 9-octadecenoic acid (Z)-, methyl ester (32.23%) was the main compound of Aloe saudiarabica while methyl 9-octadecenoate (17.28%) was the main compound of Aloe shadensis. In conclusion, the in vitro evaluation of Aloe saudiarabica and Aloe shadensis methanolic extraction showed low cytotoxicity on the viability of A-549, MCF-7 and HepG2 cell lines.

Download Full-text

Cytotoxic activity and anti-cancer potential of Ontario grown onion extracts against breast cancer cell lines

Functional Foods in Health and Disease ◽

10.31989/ffhd.v8i3.408 ◽

2018 ◽

Vol 8 (3) ◽

pp. 159 ◽

Cited By ~ 1

Author(s):

Meghan Fragis ◽

Abdulmonem I. Murayyan ◽

Suresh Neethirajan

Keyword(s):

Breast Cancer ◽

Cytotoxic Activity ◽

Cell Lines ◽

Cancer Cell ◽

Breast Cancer Cell ◽

Cancer Cell Lines ◽

Breast Cancer Cell Lines ◽

Cytotoxic Activities ◽

Cancer Line ◽

Mcf 7

Background: Breast cancer is the most commonly diagnosed cancer and the second leading cause of cancer deaths among Canadian women. Cancer management through changes in lifestyle, such as increased intake of foods rich in dietary flavonoids, have been shown to decrease the risk associated with breast, liver, colorectal, and upper-digestive cancers in epidemiologic studies. Onions are high in flavonoid content and one of the most common vegetables. Additionally, onions are used in most Canadian cuisines.Methods: We investigated the effect of five prominent Ontario grown onion (Stanley, Ruby Ring, LaSalle, Fortress, and Safrane) extracts on two subtypes of breast cancer cell lines: a triple negative breast cancer line MDA-MB-231 and an ER+ breast cancer line MCF-7.Results: These onion extracts elicited strong anti-proliferative, anti-migratory, and cytotoxic activities on both the cancer cell lines. Flavonoids present in these onion extracts induced apoptosis, cell cycle arrest in the G2/M phase, and a reduction in mitochondrial membrane potential at dose-dependent concentrations. Onion extracts were more effective against MDA-MB-231 compared to the MCF-7 cell line. Conclusion: In this study, we investigated the extracts synthesized from Ontario-grown onion varieties in inducing anti-migratory, cytostatic, and cytotoxic activities in two sub-types of human breast cancer cell lines. Anti-tumor activity of these extracts depends upon the varietal and can be formulated into nutraceuticals and functional foods for the wellbeing of cancer patients. Overall, the results suggest that onion extracts are a good source of flavonoids with anti-cancerous properties.Keywords: onion extracts; flavonoids; anti-proliferative; breast cancer; cytotoxic activity

Download Full-text

Design, Synthesis and Cytotoxicity Evaluation of New 3, 5-Disubstituted-2-Thioxoimidazolidinones

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520618666171129213838 ◽

2018 ◽

Vol 18 (4) ◽

pp. 573-582 ◽

Cited By ~ 1

Author(s):

Khaled R.A. Abdellatif ◽

Mostafa M. Elbadawi ◽

Mohammed T. Elsaady ◽

Amer A. Abd El-Hafeez ◽

Takashi Fujimura ◽

...

Keyword(s):

Breast Cancer ◽

Cell Line ◽

Cell Lines ◽

Cancer Cell ◽

Topoisomerase I ◽

Cancer Cell Line ◽

Cytotoxic Agents ◽

Dependent Manner ◽

Human Lung Fibroblast ◽

Mcf 7

Background: Some 2-thioxoimidazolidinones have been reported as anti-prostate and anti-breast cancer agents through their inhibitory activity on topoisomerase I that is considered as a potential chemotherapeutic target. Objective: A new series of 3,5-disubstituted-2-thioxoimidazolidinone derivatives 10a-f and their S-methyl analogs 11a-f were designed, synthesized and evaluated for cytotoxicity against human prostate cancer cell line (PC-3), human breast cancer cell line (MCF-7) and non-cancerous human lung fibroblast cell line (WI-38). </P><P> Results and Method: While compounds 10a-f showed a broad range of activities against PC-3 and MCF-7 cell lines (IC50 = 34.0 – 186.9 and 24.6 – 147.5 µM respectively), the S-methyl analogs 11a-f showed (IC50 = 22.7 – 198.5 and 16.9 – 188.2 µM respectively) in comparison with 5-fluorouracil (IC50 = 60.7 and 40.7 µM respectively). 11c (IC50 = 22.7 and 29.2 µM) and 11f (IC50 = 28.7 and 16.9 µM) were the most potent among all compounds against both PC-3 and MCF-7 respectively with no cytotoxicity against WI-38. Conclusion: The newly synthesized compounds showed good activity against PC-3 and MCF-7 cell lines in comparison with 5-fluorouracil. Compounds 11c and 11f bound with human topoisomerase I similar to its known inhibitors and significantly inhibited its DNA relaxation activity in a dose dependent manner which may rationalize their molecular mechanism as cytotoxic agents.

Download Full-text

Bimetallic Iron–Palladium Catalyst System as a Lewis-Acid for the Synthesis of Novel Pharmacophores Based Indole Scaffold as Anticancer Agents

Molecules ◽

10.3390/molecules26082212 ◽

2021 ◽

Vol 26 (8) ◽

pp. 2212

Author(s):

Mohammad Shahidul Islam ◽

M. Ali ◽

Abdullah Mohammed Al-Majid ◽

Abdullah Saleh Alamary ◽

Saeed Alshahrani ◽

...

Keyword(s):

Prostate Cancer ◽

Cell Line ◽

Cell Lines ◽

Cancer Cell ◽

Anticancer Agents ◽

Palladium Catalyst ◽

Cancer Cell Line ◽

Catalyst System ◽

Mcf 7 ◽

Iron Palladium

The Friedel–Crafts reaction between substituted indoles as nucleophiles with chalcones-based benzofuran and benzothiophene scaffolds was carried out by employing a highly efficient bimetallic iron–palladium catalyst system. This catalytic approach produced the desired bis-heteroaryl products with low catalyst loading, a simple procedure, and with acceptable yield. All synthesized indole scaffolds 3a–3s were initially evaluated for their cytotoxic effect against human fibroblast BJ cell lines and appeared to be non-cytotoxic. All non-cytotoxic compounds 3a–3s were then evaluated for their anticancer activities against cervical cancer HeLa, prostate cancer PC3, and breast cancer MCF-7 cell lines, in comparison to standard drug doxorubicin, with IC50 values 1.9 ± 0.4 µM, 0.9 ± 0.14 µM and 0.79 ± 0.05 µM, respectively, and appeared to be moderate to weak anticancer agents. Fluoro-substituted chalcone moiety-containing compounds, 3b appeared to be the most active member of the series against cervical HeLa (IC50 = 8.2 ± 0.2 µM) and breast MCF-7 cancer cell line (IC50 = 12.3 ± 0.04 µM), whereas 6-fluroindol-4-bromophenyl chalcone-containing compound 3e (IC50 = 7.8 ± 0.4 µM) appeared to be more active against PC3 prostate cancer cell line.

Download Full-text