Natural Products as Cytotoxic Agents in Chemotherapy against Cancer

Nature continues to produce a great wealth of natural molecules endowed with cytotoxic activity toward a large panel of tumor cells. Some of these molecules are used in chemotherapy, and others have shown great anti-tumor and anti-metastatic potential in preclinical trials. This review discusses some examples of these molecules that have been studied in our laboratory and others. We report a differential cytotoxic activity of some monoterpenes (carvacrol, tymol, carveol, carvone, and isopulegol) against a panel of tumor cell lines. The carvacrol was the most cytotoxic molecule both in vitro and in vivo as demonstrated by preclinical studies using the DBA2/P815 mice model. On the other hand, polyphenols were also studied with respect to their cytotoxic effects. Interestingly, these compounds showed a prominent cytotoxic activity toward a panel of cancer cells with differential molecular mechanisms. In addition, we report a very strong antitumor efficacy of artemisinin, a sesquiterpen lactone from Artemisia annua, together with an antimetastatic potential as demonstrated by preclinical experiments. Furthermore, some of the molecular mechanisms involved in these effects are described

Bioactive Constituents, Antioxidant Activity and in Vitro Cancer Cell Cytotoxicity of Moroccan Prickly Pear (Opuntia ficus indica L.) Juices

Several physico-chemical properties such as fruit pulp weight percentage, acidity, pH, soluble solid content,Antioxidant activity, total phenolic, flavonoid, flavonol and betalain content of nine selected promising cactuspear (Opuntia ficus indica L.) accessions were determined. The antioxidant capacity was assessed by means oftwo different methods: the 2,2-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (Trolox equivalent antioxidantcapacity) (ABTS) method and the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical method. The results showedqualitative and quantitative differences in the physico-chemical characteristics of cactus pear accessions. Totalphenolics and flavonoids content were found between 354.37 and 643.66 ?g gallic acid eq/g and 24.67 and 49.03?g catechin eq./g dry weight basis. The in vitro cytotoxicity was measured toward P-815 cell line by the growthinhibition assay determined by the MTT viability assay. We found that juice of different cultivars exert a dosedependentgrowth inhibition against P-815 cell line. The results provide important information on how to makethe best use of cactus pear genotypes investigated for different uses, which is of significance for bothtechnological research and processing practice.Keywords: prickly pears Juices acidity, sugar content, phenolics, flavonoids, flavonols, betalains, antioxidantactivity, anticancer effec

Chemical Composition and Cytotoxic and Antibacterial Activities of the Essential Oil of Aloysia citriodora

The aim of this work is to investigate the in vitro cytotoxic and antibacterial effects of the essential oils of Aloysia citriodora Palau, harvested in different regions of Morocco. The chemical profile was established using gas chromatography-mass spectrometry analysis. The cytotoxic activity against P815, MCF7, and VERO cell lines as well as the normal human peripheral blood mononuclear cells (PBMCs) was evaluated using the MTT assay. Standard, ATCC, strains of bacteria (Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa) were cultivated in Muller Hinton media. Then, agar disc diffusion, minimum inhibitory concentrations (MICs), and minimal bactericidal concentrations (MBCs) were determined using microdilution method. The essential oils obtained were predominantly composed of β-spathulenol (15.61%), Ar-curcumene (14.15%), trans-caryophyllene oxide (14.14%), and neral (10.02%). The results of the assays showed that the cytotoxic effect of the essential oil of A. citriodora was high on P815 and moderate on MCF7 and on VERO cell lines. However, no cytotoxic effect was observed on PBMCs. On the other hand, essential oils showed a significant antimicrobial activity against both Gram-negative and Gram-positive bacteria. MICs ranged between 2.84 and 8.37 mg/ml. Essential oil of A. citriodora leaves possesses significant antibacterial effect and cytotoxic activity against tumor cell lines

Hemisynthesis and evaluation of pharmacological activities of carvacrol-derivatives

Hemi-synthesis, a process widely used in pharmacological research, consists of a modification in the chemical structure of a natural product in order to improve its activity and/or to reduce its side effects. Two carvacrol-derivatives (P1 and P2) have been synthetized using reactions of alkylation by binding alkan groups at the hydroxyl group of carvacrol. NMR analysis was performed for synthetized derivatives to confirm the success of the reactions. Then, cytotoxic activity, against two tumour cell lines (P-815 and MCF-7), and antibacterial activity of carvacrol, P1 and P2 were performed. Cytotoxicity was measured using the colourimetric methyl tetrazolium test (MTT) and antimicrobial activity was measured using the diffusion technique on solid media and the determination of CMI on liquid media. Our results show that chemical modifications made on carvacrol have no effect on its antitumor activity. However, an important decrease of its antibacterial activity was observed, especially for P1. Our results suggest that hydroxyl group at this position of the molecule may be responsible for carvacrol antibacterial activity, while the other parts of the molecule may be responsible for its antitumor activity. On the other hand, introduced modifications may affect mechanism of action of the molecules as well as its pharmacokinetics properties

Comparative Phytochemical Analysis of Essential Oils from Different Biological Parts of Artemisia herba alba and Their Cytotoxic Effect on Cancer Cells.

Carrying out the chemical composition and antiproliferative effects against cancer cells from different biological parts of Artemisia herba alba.Essential oils were studied by gas chromatography coupled to mass spectrometry (GC-MS) and their antitumoral activity was tested against P815 mastocytoma and BSR kidney carcinoma cell lines; also, in order to evaluate the effect on normal human cells, oils were tested against peripheral blood mononuclear cells PBMCs.Essential oils from leaves and aerial parts (mixture of capitulum and leaves) were mainly composed by oxygenated sesquiterpenes 39.89% and 46.15% respectively; capitulum oil contained essentially monoterpenes (22.86%) and monocyclic monoterpenes (21.48%); esters constituted the major fraction (62.8%) of stem oil. Essential oils of different biological parts studied demonstrated a differential antiproliferative activity against P815 and BSR cancer cells; P815 cells are the most sensitive to the cytotoxic effect. Leaves and capitulum essential oils are more active than aerial parts. Interestingly, no cytotoxic effect of these essential oils was observed on peripheral blood mononuclear cells.Our results showed that the chemical composition variability of essential oils depends on the nature of botanical parts of Artemisia herba alba. Furthermore, we have demonstrated that the differential cytotoxic effect depends not only on the essential oils concentration, but also on the target cells and the botanical parts of essential oils used

Studies on the Dual Cytotoxicity and Antioxidant Properties of Berberis vulgaris

The present study attempts to investigate the cytotoxic activity of ethanol and ethyl acetate extracts of the Moroccan Berberis vulgaris and its major component berberine, together with exploring their antioxidant properties. It also consists of studying the combination effect of berberine and S-nitroso-N-acetylpenicillamine (SNAP), a nitric oxide (NO) donor, against the human breast adenocarcinoma cell line (MCF-7). Using the MTT assay, we report a differential cytotoxic effect of ethanol and ethyl acetate extracts since the ethanol extract is more cytotoxic than the ethyl acetate one, with IC50 = 3.54 μg/mL and 596.71 μg/mL, respectively. Interestingly, no cytotoxic effect was observed against normal cells. Furthermore, these extracts showed a remarkable antioxidant activity as measured by the DPPH free radicals scavenging assay. In fact, the IC50 values are 69.65 μg/mL and 77.75 μg/mL for the ethanol and ethyl acetate extracts, respectively. In addition, several concentrations of berberine, when combined with the NO donor used at IC30, induced a synergistic cytotoxic activity at concentrations ranging from 8.40 μM to 33.60 μM, as revealed by the combination index values, using the Chou–Talalay method. However, at the other concentrations tested, an antagonistic effect was observed. The observed cytotoxicity was related to apoptosis induction as demonstrated by the annexin-V-streptavidin FITC-staining analysis

Effect of essential oils from different organs plant of <i>Artemisia herba alba</i> against normal cells (PBMCS) and cancer cell lines (P815, BSR).

<p>EOC: essential oils of capitulum; EOL: essential oils of leaves; EOAP: essential oils of aerial parts (mixture of leaves and capitulum). Bar graph shows the mean percentage ± SD. *P < 0.05.</p

Hemisynthesis and evaluation of pharmacological activities of carvacrolderivatives

537-542Hemi-synthesis, a process widely used in pharmacological research, consists of a modification in the chemical structure of a natural product in order to improve its activity and/or to reduce its side effects. Two carvacrol-derivatives (P1 and P2) have been synthetized using reactions of alkylation by binding alkan groups at the hydroxyl group of carvacrol. NMR analysis was performed for synthetized derivatives to confirm the success of the reactions. Then, cytotoxic activity, against two tumour cell lines (P-815 and MCF-7), and antibacterial activity of carvacrol, P1 and P2 were performed. Cytotoxicity was measured using the colourimetric methyl tetrazolium test (MTT) and antimicrobial activity was measured using the diffusion technique on solid media and the determination of CMI on liquid media. Our results show that chemical modifications made on carvacrol have no effect on its antitumor activity. However, an important decrease of its antibacterial activity was observed, especially for P1. Our results suggest that hydroxyl group at this position of the molecule may be responsible for carvacrol antibacterial activity, while the other parts of the molecule may be responsible for its antitumor activity. On the other hand, introduced modifications may affect mechanism of action of the molecules as well as its pharmacokinetics properties