Source Of Natural Anticancer Agents Research Articles

Evaluation of Antioxidant, Antimicrobial, and Anticancer Properties of Onion Skin Extracts

Onion skins (OS) are a by-product of onion processing that causes both biological and environmental problems. Thus, OS could be used sustainably and as means of circular economy since they contain valuable bioactive compounds that can be used for the production of high-added-value products. This study aims to evaluate the potential antioxidant, antimicrobial, and anticancer properties of onion OS crude extracts. The extracts were prepared using different solvents (i.e., water, ethanol, and their mixtures) and evaluated for their total phenolic content and phytochemical composition, their antioxidant activity (using the DPPH radical scavenging assay, the ferric reducing antioxidant power (FRAP) assay, and the hydrogen peroxide scavenging assay), anti-inflammatory properties, as well as for their antimicrobial (against Listeria monocytogenes, Escherichia coli O157:H7, Bacillus cereus, Enterococcus faecalis, Pseudomonas aeruginosa, Staphylococcus aureus, Salmonella typhimurium, and Yersinia enterocolitica) and anticancer (against human breast cancer cells (MCF-7) and human glioblastoma cells (U-87 MG)) activity. The results revealed that the extracts contained a significant amount of phenolic compounds, ranging between 348.71 and 795.11 mg gallic acid equivalents per g of dry weight. The extracts showed promising cytotoxic effects (up to ~40%) against cancer cell lines, indicating their potential as a natural source of anticancer agents. Additionally, the extracts exhibited strong antioxidant and antimicrobial activity against the tested microorganisms. The findings of this study suggest that OS crude extracts could be a promising candidate for developing natural functional foods and pharmaceuticals. They could be used as natural alternatives for the prevention and treatment of various diseases caused by oxidative stress, microbial infections, or cancer since they are a valuable source of bioactive compounds that can be used for various applications such as food preservation, nutraceuticals, and pharmaceuticals.

Essential oil of Ruta chalepensis L. from Djibouti: Chemical Analysis and Modeling of In Vitro Anticancer Profiling

Ruta chalepensis L. (Rutaceae) is a tropical medicinal plant traditionally used in the Republic of Djibouti to treat several diseases, including tumors. In this study, the anticancer activities of this plant from Djibouti were investigated according to an in vitro evaluation method and statistical modeling. The results obtained will make it possible to complete the previous work already published on this genus of plant, in particular by using untested cancer cell lines, such as U87-MG, U2OS, RT4, PC3, NCI-N87, MRC-5, MIA-Paca2, K562, JIMT-T1, HEK293, HCT116, A549, and A2780. The main volatile compound turned out to be 2-undecanone (51.3%). Correlation modeling was performed from the principal component analysis (PCA) of IC50 of the essential oil and four active substances (vinblastine, doxorubicin, combrestatin A4, and monomethyl auristatin E) versus the cancer cell lines tested, which confirmed the effectiveness of the oil against 6 lines: U2OS, NCI-N87, MRC-5, MIA-Paca2, JIMT-T1, and HEK293. These data reveal promising prospects for good biomass management through the future exploitation of the R. chalepensis L. essential oil as a potential source of natural anticancer agents for targeted investigations.

Quercetin-Rich Extracts from Onions (Allium cepa) Play Potent Cytotoxicity on Adrenocortical Carcinoma Cell Lines, and Quercetin Induces Important Anticancer Properties.

Adrenocortical carcinoma (ACC) is a rare subtype of cancer, with a poor prognosis in children and adults. Mitotane is the only approved adrenolytic drug for the treatment of ACC, which has controversies regarding its efficacy and side effects on patients. Onion (Allium cepa), a worldwide consumed food, is associated with many health benefits. Along with its glycosides, the flavonoid quercetin is abundant in onions. After evaluating the cytotoxicity of A. cepa extracts on adrenocortical carcinoma cell line (H295R), the rich quercetin fractions had better results. Then, we aimed to compare the quercetin vs. mitotane effectiveness, using adrenocortical carcinoma cell lines H295R and SW-13. Quercetin showed a higher cytotoxicity response on both cancerous cell lines after 10 µM concentration, while mitotane only after 30 µM. Cell cycle dynamics were altered upon quercetin treatments, with G2 phase increase with 30 µM of quercetin on H295R cell line and G1 arrest on SW-13 cell line with 15 µM. Early and late apoptosis, alongside intracellular calcium, were increased on SW-13 treated with 30 µM of quercetin, and ROS rates were reduced by quercetin on H295R. Therefore, quercetin-rich onions have the potential to be a natural source of anticancer agents for adrenocortical carcinoma.

Crocus sativus L. Tepal Extract Induces Apoptosis in Human U87 Glioblastoma Cells.

Crocus sativus (C. sativus) is considered as the costliest spice and an important medicinal plant. Herein, we investigated the effects of tepal extract (TE) of C. sativus on the viability of the human glioblastoma cells. Results revealed that TE significantly (P < 0.05) inhibited the proliferation of U87 glioblastoma cells in a dose-dependent manner with comparatively lower toxic effects against normal astrocytes. The IC50 of TE against U87 glioblastoma cells was found to be 130 μg/mL as compared to 600 μg/mL against normal astrocytes. TE also inhibited the colony formation of U87 cells significantly (P < 0.05). The AO/EB and Annexin V/PI staining assays indicated that TE stimulated apoptosis in U87 cells dose dependently. The early and late apoptotic U87 cells increased from 0.66% and 2.3% at control to 14.2% and 21.4% at 260 μg/mL of TE. Moreover, TE caused upregulation of Bax and suppression of Bcl-2. Wound healing assay showed that migration of the U87 cells was suppressed significantly (P < 0.05) at 80 μg/mL of TE. Taken together, these results suggest that TE exhibits antiproliferative effects against U87 glioma cells and may prove to be an important source of natural anticancer agents.

Antioxidant and antineoplastic activities of leaves of Hibiscus sabdariffa Lina against Ehrlich ascites carcinoma cells in Swiss albino mice

Background: Since chemical anticancer drugs are found to have adverse effect on body, nowadays people are motivated towards natural agents to treat cancer. Fruits and vegetables are potential source of natural anticancer agents that protect our body against cancer by scavenging and neutralizing free radicals. Objective: The study was aimed to explore antioxidant and anticancer properties of methanolic extract of leaves of Hibiscus sabdariffa L. (MEHSL). Methods: In vitro assays were used to examine the different types of phytochemical content and antioxidant properties of MEHSL. In vitro and in vivo assays were performed to study the effects of MEHSL on Ehrlich ascites carcinoma (EAC) cells. Chemical constituents were also analyzed by GC–MS. Results: Total phenolic and flavonoid contents of MEHSL were found to be 26.23±0.30 and 131.13±1.40 mg/g of extract in terms of gallic acid and catechin equivalent, respectively. The MEHSL exhibited remarkable scavenging effect on DPPH, ABTS, nitric oxide scavenging activity and inhibition of lipid peroxidation with IC50 values 6.768, 11.54, 29.84 and 17.55, respectively, compared to the positive control, catechin. In vitro cytotoxic study shows that MEHSL reduced the viability of Ehrlich ascites carcinoma (EAC) cells in dose dependent manner. In in vivo, significant inhibition of EAC cells growth and proliferation, reduction of tumor weight and increased of survival time of EAC-bearing mice were noted following by intraperitoneal MEHSL treatment at the doses of 5 and 10 mg/ kg/day (p&lt;0.05). Moreover, the MEHSL also altered the depleted hematological parameters like RBC, WBC, and percentage of hemoglobin (Hb %) of EAC bearing mice towards normal. Furthermore, administration of MEHSL induced apoptosis of EAC cells as observed in Hoechst-33342 stained cells under fluorescence microscope. Hexadecanoic acid, methyl ester (2.845%), hexadecanoic acid (9.858%), linolenic acid methyl ester (2.142%), 9,12- -octadecadien -1-Ol (2.063), alpha-glyceryl linolenate (6.138), arachidic acid (23.280%) and phthalic acid, 6-ethyloct-3-yl 2-ethylhexyl ester (74.926%) were identified as the major constituents of MEHSL by GC-MS analysis. Conclusion: Findings of the present study suggested that the leaves of H. sabdariffa can therefore be considered as a promising resource in cancer chemotherapy. Bangladesh Med Res Counc Bull 2021; 47(2): 156-164

Solanum nigrum Ethanolic Extract (SNE) Increases Cytotoxic Activity of Doxorubicin on MCF-7 Cell

Leunca (Solanum nigrum L.) is a potential source of natural anticancer agents. Solanum nigrum L. ethanolic extract (SNE) has cytotoxic activity in several cancer cell lines. We aimed to evaluate the ability of SNE to increase MCF-7 cell sensitivity to doxorubicin as a chemotherapeutic agent for breast cancer. Cell viability of SNE and its combination treatment with doxorubicin were conducted by 3-(4,5-dimethylthiazol-2-yl)-2.5-diphenyltetrazolium bromide (MTT) assay, and apoptosis assay was analyzed by Ethidium bromide-acridine orange method. The SNE showed a cytotoxic effect in the MCF-7 cell line with IC50 50 μg/mL. Combination treated DOX-SNE resulted in a combination index (CI) value of 0.21, indicating strong synergism SNE and doxorubicin. The SNE 25 μg/mL combined with doxorubicin 100 nM optimally induced apoptosis of MCF-7 cells. We concluded that SNE is the potential to be developed as a co-chemotherapeutic agent through apoptosis induction though the molecular mechanism need to explore.Keywords: Solanum nigrum L. herb ethanolic extract, doxorubicin, MCF-7, apoptosis.

Preclinical anticancer studies on the ethyl acetate leaf extracts of Datura stramonium and Datura inoxia

BackgroundCancer is a horrific disease relentlessly affecting human population round the globe. Genus Datura encompasses numerous species with reported medicinal uses. However, its potential as a source of natural anticancer agents is yet to be determined. Datura stramonium (DS) and Datura inoxia (DI) are the two species chosen for this study.MethodsTotal phenolic and flavonoid content (TPC and TFC) as well as antioxidant activity were assessed through colorimetric method. Polyphenolic quantification was done by RP-HPLC. Following extract standardization ethyl acetate leaf extracts of both species (DSL-EA and DIL-EA) were chosen for anticancer studies. In vitro cytotoxicity using various models including cancer cell lines was monitored. Following toxicity studies, benzene (0.2 ml) was used to induce leukemia in Sprague-Dawley rats. Extracts were orally administered to preventive (100 and 200 mg/kg) and treatment (200 mg/kg only) groups. The antileukemic potential of extracts was assessed through haematological, biochemical, endogenous antioxidants and histological parameters.ResultsSignificant TPC and TFC were estimated in DSL-EA and DIL-EA. RP-HPLC quantified (μg/mg extract) rutin (0.89 ± 0.03), gallic acid (0.35 ± 0.07), catechin (0.24 ± 0.02) and apigenin (0.29 ± 0.09) in DSL-EA while rutin (0.036 ± 0.004) and caffeic acid (0.27 ± 0.03) in DIL-EA. Both extracts exhibited significant brine shrimp cytotoxicity (LC50 < 12.5 μg/ml). DIL-EA exhibited greater cytotoxicity against PC-3, MDA-MB 231 and MCF-7 cell lines (IC50 < 3 μg/ml in each case) as well as higher protein kinase inhibitory action (MIC: 25 μg/disc) compared to DSL-EA. Leukemia induced in rats was affirmed by elevated serum levels of WBCs (7.78 ± 0.012 (× 103) /μl), bilirubin (7.56 ± 0.97 mg/dl), Thiobarbituric acid reactive substances (TBARs) (133.75 ± 2.61 nM/min/mg protein), decreased RBCs (4.33 ± 0.065 (× 106)/μl), platelets (344 ± 3.19 (× 103)/μl), total proteins (2.14 ± 0.11 g/dl), Glutathione S-transferases (GST) (81.01 ± 0.44 nM/min/ml), endogenous antioxidant enzymes levels and abnormal liver and kidney functionality in disease control rats. Both species revealed almost identical and significant (p < 0.05) alleviative effects in benzene induced leukemia.ConclusionComprehensive screening divulged the tremendous potential of selected species as potent source of natural anticancer agents in a variety of cancers particularly leukemia. Present study might provide useful finger prints in cancer research and mechanistic studies are prerequisite in logical hunt of this goal.

Estimation of anticancer effect of methanolic extract of Artemisia herba alba on human cancer cell lines

Artemisia (Asteraceae family) has been reported to possess different bioactive phytochemicals including phenols, sesquiterpene lactones and flavonoids. The aim of this study was to estimate the anti-proliferative activity of the methanolic extract of Artemisia herba alba using in vitro assays on two of human cancer cell lines compared with the normal cell lines. The obtained results indicated that A.herba alba extract showed highly cytotoxic and anti-proliferative effects on tested human cancer cells as revealed by measuring viable mitochondrial oxidation of [3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay] (MTT assay). The observed (-IC50-) or the half-maximal inhibitory concentration of A. herba alba extract in the human hepatocellular carcinoma (HepG2) was 50.34 μg/ml, while in the lung cancer cell line (A549) it was 29.23 μg/ml. In contrast, the normal liver cells (THLE2) as well as lung normal cells showed very low sensitivity toward tested extract where the IC50 were 1250μg/ml and 1915 μg/ml, respectively. However, flow cytometric analysis for cell cycle using propidium iodide staining revealed increment of G2/M phase cell cycle arrest after treatment of HepG2 cells with A. herba alba extract. At the molecular level, the quantitative real time-PCR technique was used to investigate the alteration of gene expression after exposure of HepG2 cell line to A. herba alba extract by measuring levels of mRNA for p53, Bax, and Bcl-2 genes expression. The apoptotic mechanism was activated by the crude extract of A. herba alba extract included up-regulation of p53 and Bax and down-regulation of Bcl-2 expression levels. However, no cytotoxic effect was recorded after exposure of normal cell lines to the plant extract. These data indicated that A. herba alba extract possess anti-proliferative effect by a cell cycle arrest at the G2/M phase and apoptosis mediated cytotoxicity in carcinoma cells. These results suggested that A.herba alba could contain one or more effective anti-cancer compound(s) and can be used as a natural source of anticancer agents.

Chitosan Nanoparticles as a Carrier for Indigofera intricata Plant Extract: Preparation, Characterization and Anticancer Activity

Background: Cancer is one of the major causes of the death and affects people of all ages throughout the world. The drugs that are currently available to treat cancer have many side effects. Hence, there is considerable scientific interest in the continuing discovery of new anticancer agents from natural sources. The aim of this study was to prepare and characterize nanoparticles combining Indigofera intricata crude alcoholic extract and chitosan and to evaluate the anticancer cell proliferative activity for both extract and nanoparticles. Methods: Dried alcoholic extract was prepared and characterized for its phenolic and flavonoid contents. Chitosan extract nanoparticles was prepared by ionic gelation method and characterized by thin layer chromatography (TLC), Fourier-transform infrared spectroscopy (FTIR), particle size and zeta-potential analysis. The anticancer cell proliferative activities of both plant extract and nanoparticles at different concentrations were evaluated using breast cancer cell line (MCF 7). Results: The alcoholic extract showed high contents from both phenolic and flavonoid constituents (15 % and 22 % respectively). The interaction of polyphenolic compounds of the extract with chitosan was confirmed by the TLC and FTIR results. The particle size and zeta-potential of nanoparticles found to be 400.6nm ± 101.8 nm and +42.1 mV ± 9.27 mV respectively. The plant extract showed the lowest cell viability of 45.21% ± 4.8% at the highest dose (250 mg) tested in this investigation. Almost 500-fold reduction (from 250 mg to 0.5 mg) in the extract concentration required to achieve same anticancer cell proliferative activity when formulated as nanoparticles. Also 2.5 mg extract containing nanoparticles showed similar anticancer cell proliferative activity as 5 mg 5-FU. Conclusion: Our results revealed that traditional medicinal plants could be an excellent source of natural anticancer agents and the chitosan-extract nanoparticles is a promising formulation strategy to enhance their clinical effectiveness.

ASSESSMENT OF CYTOTOXIC AND ANTICANCER ACTIVITY OF Zygophyllum album AND Suaeda palastina EXTRACTS ON HUMAN LIVER CANCER CELL LINES

In this study, anticancer activity of Zygophyllum album and Suaeda palastina extracts was evaluated. Dichloromethane, methanol and hot water were used as solvents for extraction. Results indicated that the highest half-maximal inhibitory concentration (IC50) on human lung carcinoma (A549) cell lines was achieved by dichloromethane extracts of Z. album and S. palastina (70.48 μg/ml and 34.82 μg/ml respectively) compared to methanolic and hot water extracts. Furthermore, dichloromethane extracts of both plants had antiproliferative effect and highly cytotoxicity on human cancer cells. IC50 of Z. album was 27.74 μg/ml in the human hepatocellular carcinoma (HepG2), while IC50 of S. palaestina was 30.76 μg/ml with no cytotoxic activity on normal cell lines. In conclusion, these results suggest that Z. album and S. palaestina could be a good candidate species as a natural source of anticancer agents.

Extracts of Hypsizygus tessellatus (white var.) caps inhibited MCF-7 and MDA-MB-231 cell lines proliferation

Cancer management is associated with serious side-effects due to the harmful nature of radiation and chemotherapy on the body cells. These side-effects have necessitated the need for diversifying the alternative or complementary sources of cancer therapy. Natural products have been on the front line as alternative sources of anticancer agents and have attracted much attention in recent times. In this study, the anticancer activity of Hypsizygus tessellatus (white var.) caps (also known as Bunapi shimeji) extracted with acetone and ethyl acetate was evaluated in vitro against MDA-MB-231 and MCF-7 (breast cancer cell lines) and MCF-10a (Vero or normal breast cells). Likewise, the free radical scavenging and metal reducing activities of the extract were evaluated through in vitro chemical-based methods. Furthermore, the phytochemical compositions of the extracts were determined through LC–MS-QTOF-assisted mass spectroscopy. The results of this study indicated that acetone fraction had better radical scavenging activity against DPPH (IC50 = 0.76 mg/mL) and H2O2 (IC50 = 0.84 mg/mL) than ethyl acetate fraction against DPPH (IC50 = 1.10 mg/mL) and H2O2 (IC50 = 1.26 mg/mL) (p < 0.05). Additionally, the acetone fraction was observed to have more antiproliferative effects against MCF-7 (IC50 = 0.051–0.055 mg/mL) and MDA-MB-231 (IC50 = 0.122–0.131 mg/mL) compared to the ethyl acetate fraction against MCF-7 (IC50 = 0.075–0.096 mg/mL) and MDA-MB-231 (IC50 = 0.161–0.164 mg/mL) (p < 0.05). Both extracts generally had less effect on MCF-10a cells. Thus, these results suggested that Bunapi shimeji caps is a potential good natural source of anticancer agents.

In vitro Antiproliferation Effect of Atriplex halimus L. Crude Extract on Human Cell Lines by Induction of Apoptosis and G2/M phase Arrest.

Current clinical ways include the usage of medicinal plants as therapeutic agents in a large scale of applications. The present study is focused on the anticancer activity of the methanolic extract of Atriplex halimus and the likely underlying mechanisms were also investigated. Results exhibited that the extract had an antiproliferative effect and highly cytotoxicity in cancer cells, Human hepatocellular carcinoma (HepG2) (IC50 = 54.86 μg/ml), against the human breast adenocarcinoma cell line (MCF-7) with IC50 value of 153.6 μg/ml and lung cancer cell line (A549) (IC50 = 101.9 μg/ml). In contrast, this extract exhibited no induces growth inhibition (did not cytotoxic activity) on normal cell lines. Flow cytometric analysis of propidium iodide staining detected that the treatment of HepG2 cells with A. halimus led to increase G2/M phase cell cycle arrest. The data obtained from acridine orange/ethidium bromide(AO/EtBr) protocol showed the morphological characters of apoptosis such as apoptotic bodies, nuclear fragmentation and chromatin condensation; in addition, necrotic cells were observed. The real time-PCR and western blotting techniques were used to measure the mRNA levels of p53, Bax, and Bcl-2 genes and proteins expression. The apoptotic process triggered by A. halimus involved the upregulation of p53 and Bax and the downregulation of Bcl-2 in both techniques. These data indicated that A. halimus exhibited antiproliferative effect by a cell cycle blocking at the G2/M phase and apoptosis mediated cytotoxicity in carcinoma cells. In conclusion, these results suggest that A. halimus could be a good candidate species as a natural source of anticancer agents.

Cytotoxic and Apoptotic Activities of Methanolic Subfractions of Scrophularia oxysepala against Human Breast Cancer Cell Line.

Herbs have played a positive role in medicine for thousands of years. In the current study, we investigated the cytotoxicity effects of Scrophularia oxysepala methanolic subfractions and the underlying mechanism responsible for cell death in human breast carcinoma (MCF-7 cells) and mouse fibrosarcoma (WEHI-164 cells). From 60% and 80% methanolic fractions, four subfractions (Fa, Fb, Fc, and Fd), yielded from size exclusion by Sephadex-LH20 column chromatography, were chosen. MTT assay revealed that all subfractions significantly reduced cell viability after 24 h and 36 h in a dose-dependent manner; it is worth noting that Fa and Fb subfractions had the highest cytotoxicity, with IC50 values of 52.9 and 61.2 μg/mL in MCF-7 at 24 h, respectively. ELISA, TUNEL, and DNA fragmentation assay revealed that antiproliferative effects of all subfractions were associated with apoptosis on cancer cells, without any significant effect on L929 normal cells. qRT-PCR data showed that, after 24 h treatment with IC50 concentrations of the subfractions, caspase-3 expression was increased in cancer cells while the expression of Bcl-2 was decreased. S. oxysepala methanolic subfractions induce apoptosis in MCF-7 and WEHI-164 cells and could be considered as a source of natural anticancer agents.

Cytotoxic activity of kenaf (Hibiscus cannabinus L.) seed extract and oil against human cancer cell lines

To examine the cytotoxic properties of both the kenaf (Hibiscus cannabinus L.) seed extract and kenaf seed oil on human cervical cancer, human breast cancer, human colon cancer and human lung cancer cell lines. The in vitro cytotoxic activity of the kenaf (Hibiscus cannabinus L.) seed extract and kenaf seed oil on human cancer cell lines was evaluated by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and sulforhodamine B assays. Cell morphological changes were observed by using an inverted light microscope. The kenaf seed extract (KSE) exhibited a lower IC50 than kenaf seed oil (KSO) in all of the cancer cell lines. Morphological alterations in the cell lines after KSE and KSO treatment were observed. KSE and KSO possessed effective cytotoxic activities against all the cell lines been selected. KSE and KSO could be potential sources of natural anti-cancer agents. Further investigations on using kenaf seeds for anti-proliferative properties are warranted.