Anti-Hepatocellular-Cancer Activity Exerted by β-Sitosterol and β-Sitosterol-Glucoside from Indigofera zollingeriana Miq

Indigofera zollingeriana Miq (I. zollingeriana) is a widely grown tree in Vietnam. It is used to cure various illnesses. The purpose of this study was to investigate the chemical constituents of an I. zollingeriana extract and test its anticancer activity on hepatocellular cells (Huh7 and HepG2). The experimental results of the analysis of the bioactive compounds revealed that β-sitosterol (β-S) and β-sitosterol-glucoside (β-SG) were the main ingredients of the I. zollingeriana extract. Regarding anticancer activity, the β-S and β-SG of I. zollingeriana were found to exhibit cytotoxic effects against HepG2 and Huh7 cells, but not against normal human primary fibroblasts. The β-S was able to inhibit the proliferation of HepG2 and Huh7 cells in a dose-dependent manner with half-maximal inhibitory concentration (IC50) values of 6.85 ± 0.61 µg/mL and 8.71 ± 0.21 µg/mL, respectively (p < 0.01), whereas the β-SG IC50 values were 4.64 ± 0.48 µg/mL for HepG2 and 5.25 ± 0.14 µg/mL for Huh7 cells (p < 0.01). Remarkably, our study also indicated that β-S and β-SG exhibited cytotoxic activities via inducing apoptosis and activating caspase-3 and -9 in these cells. These findings demonstrated that β-S and β-SG from I. zollingeriana could potentially be developed into promising therapeutic agents to treat liver cancer.

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Naphthoquinone-based hydrazone hybrids: synthesis and potent activity against cancer cell lines

Medicinal Chemistry ◽

10.2174/1573406416666200817164308 ◽

2020 ◽

Vol 16 ◽

Author(s):

Délis Galvão Guimarães ◽

Arlan de Assis Gonsalves ◽

Larissa Araújo Rolim ◽

Edigênia Cavalcante Araújo ◽

Victória Laysna dos Anjos Santos ◽

...

Keyword(s):

Anticancer Activity ◽

Cell Lines ◽

Cancer Cell ◽

Biological Activities ◽

Supporting Electrolyte ◽

Cancer Cell Lines ◽

Molecular Structures ◽

Cytotoxic Activities ◽

Electrochemical Studies ◽

Ic50 Values

Background: Natural naphthoquinones have shown diversified biological activities including antibacterial, antifungal, antimalarial, and cytotoxic activities. However, they are also compounds with acute cytotoxicity, immunotoxicity, carcinogenesis, and cardio- and hepatotoxicity, then the modification at their redox center is an interesting strategy to overcome such harmful activity. Objective: In this study, four novel semisynthetic hydrazones, derived from the isomers α- and β-lapachones (α and β, respectively) and coupled with the drugs hydralazine (HDZ) and isoniazid (ACIL), were prepared, evaluated by electrochemical methods and assayed for anticancer activity. Method: The semisynthetic hydrazones were obtained and had their molecular structures established by NMR, IR, and MS. Anticancer activity was evaluated by cell viability determined by reduction of 3-(4,5-dimethyl-2-thiazol)-2,5-diphenyl-2H-tetrazolium bromide (MTT). The electrochemical studies, mainly cyclic voltammetry, were performed, in aprotic and protic media. Result: The study showed that the compounds 2, 3, and 4 were active against at least one of the cancer cell lines evaluated, being compounds 3 and 4 the most cytotoxic. Toward HL-60 cells, compound 3 was 20x more active than β-lapachone, and 3x more cytotoxic than doxorubicin. Furthermore, 3 showed an SI value of 39.62 for HL-60 cells. Compound 4 was active against all cancer cells tested, with IC50 values in the range 2.90–12.40 μM. Electrochemical studies revealed a profile typical of self-protonation and reductive cleavage, dependent on the supporting electrolyte. Conclusion: These results therefore indicate that compounds 3 and 4 are strong candidates as prototypes of new antineoplastic drugs.

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Design, Synthesis, and Structural Characterization of Novel Diazaphenothiazines with 1,2,3-Triazole Substituents as Promising Antiproliferative Agents

Molecules ◽

10.3390/molecules24234388 ◽

2019 ◽

Vol 24 (23) ◽

pp. 4388 ◽

Cited By ~ 3

Author(s):

Morak-Młodawska ◽

Pluta ◽

Latocha ◽

Jeleń ◽

Kuśmierz

Keyword(s):

Anticancer Activity ◽

Cell Lines ◽

Human Fibroblasts ◽

Human Tumor ◽

Design Synthesis ◽

Human Tumor Cell Lines ◽

Ic50 Values ◽

Normal Human ◽

Low Cytotoxicity

A series of novel 1,2,3-triazole-diazphenothiazine hybrids was designed, synthesized, and evaluated for anticancer activity against four selected human tumor cell lines (SNB-19, Caco-2, A549, and MDA-MB231). The majority of the synthesized compounds exhibited significant potent activity against the investigated cell lines. Among them, compounds 1d and 4c showed excellent broad spectrum anticancer activity, with IC50 values ranging from 0.25 to 4.66 μM and 0.25 to 6.25 μM, respectively. The most promising compound 1d, possessing low cytotoxicity against normal human fibroblasts NHFF, was used for gene expression analysis using reverse transcription–quantitative real-time PCR (RT–qPCR). The expression of H3, TP53, CDKN1A, BCL-2, and BAX genes revealed that these compounds inhibited the proliferation in all cells (H3) and activated mitochondrial events of apoptosis (BAX/BCL-2).

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EVALUATION OF IN VITRO CYTOTOXIC EFFECT OF VIOLACEIN PRODUCED BY NOVEL ISOLATE CHROMOBACTERIUM VACCINII CV5 AGAINST THE CERVICAL AND LUNG CANCER CELL

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2017.v10i10.20456 ◽

2017 ◽

Vol 10 (10) ◽

pp. 227 ◽

Cited By ~ 1

Author(s):

Vishnu T Santhosh ◽

Palaniswamy Muthusamy

Keyword(s):

Lung Cancer ◽

Anticancer Activity ◽

Cell Lines ◽

Cancer Cell ◽

A549 Cells ◽

Dependent Manner ◽

Concentration Dependent Manner ◽

Cytotoxicity Activity ◽

Ic50 Values

Objectives: This study investigates the in vitro anticancer activity of the violacein extracted from the Chromobacterium vaccinii CV5.Methods: Natural colorants or dyes derived from flora to fauna are believed to be safe because of nontoxic, noncarcinogenic, and biodegradable in nature. There are a number of natural pigments, but only a few are available in sufficient quantities for industrial production. The cytotoxicity activity of pigment was assessed against the cervical (HeLa) and lung cancer (A549) cell lines using the MTT assay and there by potential cytotoxic activity exhibited by the pigment was identified.Results: The result of the pigment shows potent anticancer activity on the two cancer cell lines tested in a concentration dependent manner. The potent anticancer activity was observed with the pigment with IC50 values of 26 μg/mL on HeLa and 31 μg/mL on A549 cells, respectively.Conclusion: The study is pioneering report for determining the better in vitro anticancer activity of violacein from the novel isolate C. vaccinii CV5.

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Antimicrobial Activity, Cytotoxicity and Chemical Constituents of the Freshwater Microalga Oscillatoria princeps

Biointerface Research in Applied Chemistry ◽

10.33263/briac121.961977 ◽

2021 ◽

Vol 12 (1) ◽

pp. 961-977

Keyword(s):

Antimicrobial Activity ◽

Anticancer Activity ◽

Hepg2 Cell ◽

Chemical Constituents ◽

Octadecenoic Acid ◽

Bioactive Metabolites ◽

Diethyl Ether Extract ◽

Successive Extraction ◽

Ic50 Values ◽

Promising Source

The microalgae Oscillatoria sp. are promising sources of bioactive metabolites used in both pharmaceutical and nutraceutical applications. The main objective of present study is to determine the antimicrobial activity, cytotoxicity, and chemical profile of Oscillatoria princeps r extracts and its fractions. O. princeps extracts were prepared by successive extraction method, and chemical constituents were identified using GC-MS. Diethyl ether extract (DEE) had antimicrobial activity against all tested microorganisms and the highest inhibition zones 20.7 and 20.2 mm was observed against P. aeruginosa and A. flavus, respectively. Also, DEE showed an anticancer activity with IC50 values of 35.18, 46.6, and 79.18 µg ml-1 against breast cancer (MCF7), colon cancer (HCT116), and hepatocellular carcinoma (HePG2) cell lines, respectively. By DEE fractionation, fraction F7 showed the highest antimicrobial activity followed by fraction F4 with minimum inhibitory concentration (MIC) values ranged between 0.5 and 1.9 mg ml-1. Fraction F4 recorded anticancer activity against HCT116, MCF7, and HePG2 with IC50 of 22.62, 24.43, and 102.52 µg ml-1, respectively. While fraction F7 had anticancer activity against HCT116 and MCF7 without any effect on the HePG2 cell line. GC-MS analysis of fractions F4 and F7 represented that the main compounds responsible for the bioactivity were Pentadeconic acid,4-hexadecyl ester, and 9-Octadecenoic acid in F4, while the main compounds in F7 were Quercetin 7,3',4'-trimethoxy and Methyl tetradecanoate. The study concluded that O. princeps DEE extract and fractions had a sufficient amount of bioactive compounds that possess antimicrobial and anticancer activity, which could be a promising source for pharmaceutical and nutraceutical ingredients.

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Chemical Constituents of Tibetan Herbal Medicine Pulicaria insignis and Their in vitro Cytotoxic Activities

Records of Natural Products ◽

10.25135/rnp.193.20.06.1692 ◽

2020 ◽

Vol 15 (2) ◽

pp. 91-102

Author(s):

Xinzhu Wang ◽

Peilei Hou ◽

Yanbo Qu ◽

Rizhen Huang ◽

Yan Feng ◽

...

Keyword(s):

Herbal Medicine ◽

Cell Lines ◽

Hepg2 Cells ◽

Chemical Constituents ◽

2D Nmr ◽

Cytotoxic Activities ◽

Hela Cell Lines ◽

Ic50 Values ◽

Hepg2 Cell Lines

One new phenolic derivative, 1-(4',5'-dihydroxy-2'-methylphenyl)-pentane-1,4-dione (1), along with eighteen known compounds including eight sesquiterpenoids (2–9), one triterpenoid (10), one bisdpoxylignan (11), one coumarin (12), and seven flavonoids (13–19) were isolated from the dried inflorescence of Tibetan herbal medicine Pulicaria insignis. The structure of 1 was established by spectroscopic methods, including HRESIMS, IR, 1D, and 2D NMR. All isolates were assessed for the cytotoxic activities against MGC-803, T24, HepG2, and HeLa cell lines using the MTT assay. The results showed that compound 1 displayed moderate cytotoxicity against Hela and HepG2, and compounds 3, 4, 5, 6, and 13 exhibited potential cytotoxic activities against the four cell lines with IC50 values ranging from 3.05 to 14.37 μM. Notably, compound 5 exhibited significant anti-proliferative activities against HepG2 cell lines with the IC50 values of 3.05 ± 0.36 μM. Further bioactivity investigation showed that compound 5 could block HepG2 cells in the G1 phase of the cell cycle, thereby inhibiting the growth of HepG2 cells and inducing apoptosis in HepG2 cells.

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Persicaria lapathifolia Essential Oil: Chemical Constituents, Antioxidant Activity, and Allelopathic Effect on the Weed Echinochloa colona

Plants ◽

10.3390/plants10091798 ◽

2021 ◽

Vol 10 (9) ◽

pp. 1798

Author(s):

Ahmed M. Abd-ElGawad ◽

Giuliano Bonanomi ◽

Sarah A. Al-Rashed ◽

Abdelsamed I. Elshamy

Keyword(s):

Antioxidant Activity ◽

Ascorbic Acid ◽

Essential Oil ◽

Bioactive Compounds ◽

Chemical Constituents ◽

Radical Scavenging Activity ◽

Radical Scavenging ◽

Allelopathic Effect ◽

Dependent Manner ◽

Ic50 Values

The exploration of new green, ecofriendly bioactive compounds has attracted the attention of researchers and scientists worldwide to avoid the harmful effects of chemically synthesized compounds. Persicaria lapathifolia has been reported to have various bioactive compounds, while its essential oil (EO) has not been determined yet. The current work dealt with the first description of the chemical composition of the EO from the aerial parts of P. lapathifolia, along with studying its free radical scavenging activity and herbicidal effect on the weed Echinochloa colona. Twenty-one volatile compounds were identified via GC–MS analysis. Nonterpenoids were the main components, with a relative concentration of 58.69%, in addition to terpenoids (37.86%) and carotenoid-derived compounds (1.75%). n-dodecanal (22.61%), α-humulene (11.29%), 2,4-dimethylicosane (8.97%), 2E-hexenoic acid (8.04%), γ-nonalactone (3.51%), and limonene (3.09%) were characterized as main compounds. The extracted EO exhibited substantial allelopathic activity against the germination, seedling root, and shoot growth of the weed E. colona in a dose-dependent manner, showing IC50 values of 77.27, 60.84, and 33.80 mg L−1, respectively. In addition, the P. lapathifolia EO showed substantial antioxidant activity compared to ascorbic acid as a standard antioxidant. The EO attained IC50 values of 159.69 and 230.43 mg L−1, for DPPH and ABTS, respectively, while ascorbic acid exhibited IC50 values 47.49 and 56.68 mg L−1, respectively. The present results showed that the emergent leafy stems of aquatic plants such as P. lapathifolia have considerably low content of the EO, which exhibited substantial activities such as antioxidant and allelopathic activities. Further study is recommended to evaluate the effects of various environmental and climatic conditions on the production and composition of the EOs of P. lapathifolia.

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Cytotoxic Sesquiterpenes from Sonchus oleraceus

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520620666200101152934 ◽

2020 ◽

Vol 20 (6) ◽

pp. 709-714

Author(s):

Hongying Zhang ◽

Yiding Wang ◽

Shaojiu Wang ◽

Qian Wang ◽

Tianjing Wang ◽

...

Keyword(s):

Ethyl Acetate ◽

Silica Gel ◽

Column Chromatography ◽

Chemical Constituents ◽

Live Cells ◽

Dependent Manner ◽

Caspase 9 ◽

Sonchus Oleraceus ◽

Caco2 Cells ◽

Ic50 Values

Background: Sonchus oleraceus is a large and widespread plant in the world. It is edible to humans as a leaf vegetable and is also used as a folklore medicinal herb in the treatment of infections and inflammatory disease, but limited research on its chemical constituents has been done. Objective: To isolate and identify the bioactive ingredients from S. oleraceus. Methods: 20kg of S. oleraceus was extracted twice with 75% alcohol. The concentrated extract was suspended in H2O and partitioned with petroleum ether, dichloromethane, ethyl acetate and n-butanol, respectively. The ethyl acetate phase was subjected to repeated normal chromatography on a silica gel column chromatography and eluted with a gradient of CH2Cl2-MeOH to give 12 crude fractions. Fraction 6 was subjected to ODS silica gel column chromatography, Sephadex LH-20 and HPLC to yield 1 and 2. Cell viability of 1 and 2 on A549, H292 and Caco2 cell lines were assayed by MTT method. Apoptosis analysis and apoptosis related proteins were detected subsequently. Results: Two new sesquiterpenes were isolated from S. oleraceus and identified by NMR spectra and HR-ESIMS. 1 selectively suppressed the viability of A549 and H292 cells with IC50 values of 14.2, and 19.5μM respectively, while possessing no cytotoxicity against Caco2 cells (IC50 > 100μM). 2 did not exhibit cytotoxicity against A549, H292 and Caco2 cells (IC50 > 100μM). 1 significantly decreased the density of live cells and could cause cell apoptosis at 10 and 20μM in a dose-dependent manner. After treatment of 1 for 24h, the level of cleaved caspase-3 was increased accompanied by the reduction in procaspase-3 expression, and the downregulation of Bcl-2 was associated with the enhancement of Bax expression. 1 could lead to the up-regulation of cytochrome c and activation of caspase-9. Conclusion: 1 and 2 are new sesquiterpenes from S. oleraceus. 1 could induce apoptosis in A549 and H292 cells through Bax/caspase-9 pathway.

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COMPARATIVE ANALYSIS OF THE ANTICANCER ACTIVITY OF ANGIOTENSIN RECEPTOR BLOCKERS - IRBESARTAN AND TELMISARTAN

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2018.v11i12.27948 ◽

2018 ◽

Vol 11 (12) ◽

pp. 403

Author(s):

Punnagai K ◽

Vijaybabu K ◽

Glory Josephine I ◽

Darling Chellathai David

Keyword(s):

Anticancer Activity ◽

Angiotensin Receptor Blockers ◽

A549 Cells ◽

Mitogen Activated Protein Kinase ◽

Dependent Manner ◽

Angiotensin Receptor ◽

Survival Pathway ◽

Mitogen Activated Protein ◽

Ic50 Values ◽

Receptor Blockers

Objective: Angiotensin receptor blockers (ARBs) are effective hypertensive drugs. Reduction in risk of lung cancer with ARBs was proven in clinical studies. Telmisartan and irbesartan are the second-generation ARBs. This study screens the anticancer activity of these two drugs in a dose-dependent manner using A549 cell line.Methods: Different concentrations of irbesartan and telmisartan were treated on A549 cells and the anticancer activity was evaluated through methylthiazolyldiphenyl-tetrazolium [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] cytotoxicity assay. The dot plot of the cytotoxicity results was used to extrapolate the half maximal inhibitory concentration (IC50) values. Microscopic changes in the cells post-treatment with these drugs were also recorded at ideal concentrations.Results: A reduction in cell viability was noted in A549 cells with increasing concentration of the drug. The IC50 values for irbesartan and telmisartan were 31.1 μg and 15.6 μg, respectively. Microscopic observation of the cells shows more rounded and deformed dead cells on telmisartan- and irbesartan-treated cells when compared with the untreated control.Conclusion: The results confirm the anticancer activity of both the drugs with telmisartan being more efficient. The anticancer activity could probably be due to the role of irbesartan and telmisartan in inhibiting mitogen-activated protein kinase cell survival pathway and local angiogenesis.

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Design, Synthesis, and Anticancer Activity Studies of Novel Quinoline-Chalcone Derivatives

Molecules ◽

10.3390/molecules26164899 ◽

2021 ◽

Vol 26 (16) ◽

pp. 4899

Author(s):

Yong-Feng Guan ◽

Xiu-Juan Liu ◽

Xin-Ying Yuan ◽

Wen-Bo Liu ◽

Yin-Ru Li ◽

...

Keyword(s):

Anticancer Activity ◽

Anticancer Agents ◽

Ros Generation ◽

Dependent Manner ◽

Gastric Cancer Cells ◽

Design Synthesis ◽

Chalcone Derivatives ◽

Ic50 Values ◽

Hct 116 ◽

Mcf 7

The chalcone and quinoline scaffolds are frequently utilized to design novel anticancer agents. As the continuation of our work on effective anticancer agents, we assumed that linking chalcone fragment to the quinoline scaffold through the principle of molecular hybridization strategy could produce novel compounds with potential anticancer activity. Therefore, quinoline-chalcone derivatives were designed and synthesized, and we explored their antiproliferative activity against MGC-803, HCT-116, and MCF-7 cells. Among these compounds, compound 12e exhibited a most excellent inhibitory potency against MGC-803, HCT-116, and MCF-7 cells with IC50 values of 1.38, 5.34, and 5.21 µM, respectively. The structure–activity relationship of quinoline-chalcone derivatives was preliminarily explored in this report. Further mechanism studies suggested that compound 12e inhibited MGC-803 cells in a dose-dependent manner and the cell colony formation activity of MGC-803 cells, arrested MGC-803 cells at the G2/M phase and significantly upregulated the levels of apoptosis-related proteins (Caspase3/9 and cleaved-PARP) in MGC-803 cells. In addition, compound 12e could significantly induce ROS generation, and was dependent on ROS production to exert inhibitory effects on gastric cancer cells. Taken together, all the results suggested that directly linking chalcone fragment to the quinoline scaffold could produce novel anticancer molecules, and compound 12e might be a valuable lead compound for the development of anticancer agents.

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AROMATASE INHIBITORY AND CYTOTOXIC ACTIVITIES OF CHEMICAL CONSTITUENTS FROM THE VIETNAMESE MEDICINAL PLANT BAN-CHI-LIEN (SCUTELLARIA BARBATA D. DON)

ASEAN Journal on Science and Technology for Development ◽

10.29037/ajstd.278 ◽

2017 ◽

Vol 25 (2) ◽

pp. 481-487 ◽

Cited By ~ 2

Author(s):

Do Thi Thao ◽

Le Quang Huan ◽

Do Khac Hieu ◽

Nguyen Quyet Chien ◽

Nguyen Van Hung

Keyword(s):

Medicinal Plant ◽

Human Cancer ◽

Chemical Constituents ◽

Positive Control ◽

Cytotoxic Activities ◽

Scutellaria Barbata ◽

Human Cancer Cell Lines ◽

Ic50 Value ◽

Bioassay Guided Fractionation ◽

Ic50 Values

Aromatase inhibitory and cytotoxic activities were determined for apigenin, luteolin and the new diterpene named scutebarbalactone VN, which were obtained by bioassay-guided fractionation and isolation from the methanol extract of the Vietnamese medicinal plant Banchi-lien (Scutellaria barbata D. Don). In the aromatase inhibition assay, an IC50 value of 3.36 mM was found for scutebarbalactone VN, while IC50 values of 7.2 mM and 7.95 mM were found for the positive controls aminoglutethimide and b-estradiol, respectively. In the cytotoxicity assays using a panel of human cancer cell lines, scutebarbalactone VN showed promising anticancer activity with IC50 ranging from 2.15 to 8.3 mM compared with those of the positive control ellipticine ranging from 1.0 to 2.1 mM. Apigenin and luteolin were found to be inactive in both assays.

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