Cytotoxic properties of three isolated coumarin-hemiterpene ether derivatives from artemisia armeniaca lam.

Considering multiple reports on cytotoxic activity of the Artemisia genus and its phytochemicals, in the current study A. armeniaca Lam. and the three components isolated from the plant were subjected to cytotoxic studies. Analytical fractionation of A. armeniaca aerial parts for the first time was directed to the isolation of 7-hydroxy-8-[4-hydroxy-3-methylbutoxy] comarin [armenin], 8-hydroxy-7-[4-hydroxy-3-methylbutoxy] comarin [isoarmenin] and deoxylacarol. Cytotoxicity assessed with alamalBlue[registered] assay and apoptosis was detected by PI staining and western blot analysis of Bax and PARP proteins. Extracts and all compounds exhibited cytotoxic activity against apoptosis-proficient HL-60 and apoptosis-resistant K562 cells, with the lowest cytotoxic activity on J774 cell line as non-malignant cell. Armenin as the most potent component decreased the viability of cell with IC50 of 22.5 and 71.1 micro M for K562 and HL-60 cells respectively and selected for further mechanistic study. Armenin increased the sub-G1 peak in flow cytometry histogram of HL-60 and K562 treated cells and increase in the amount of Bax protein and the cleavage of PARP in comparison with the control after treatment for 48 h in K562 treated cells verified the apoptotic activity of the armenin. Taken together, according to the finding of this study armenin was introduced as a novel cytotoxic compound with apoptotic activity, which is encouraging for further mechanistic and clinical studies

Apoptosis induction of salvia chorassanica root extract on human cervical cancer cell line

Salvia chorassanica Bunge is one of the Iranian endemic species of Salvia. There is not any reported literature on S. chorassanica. This study was designed to examine the in-vitro anti- proliferative and proapoptotic effects of the methanol extract of S. chorassanica and its fractions on HeLa cell line. Cells were cultured in EX-CELL®, an animal free medium specially designed for HeLa cell line and incubated with different concentrations of plant extracts. Cell viability was quantified by MTS assay. Apoptotic cells were determined using propidium iodide [PI] staining of DNA fragmentation by flow cytometry [sub-G1 peak]. Activity of caspase -3, -8 and -9 was measured by the caspase colorimetric kit assay. S. chorassanica inhibited the growth of malignant cells and the CH[2]Cl[2] fraction was determined as the most cytotoxic fraction in comparison with other fractions. The calculated IC[50] values for methanol extract, n-hexane, and CH[2]Cl[2] and EtOAc fractions were 8.841, 5.45, 2.38, and 58.03 [micro]g/mL, respectively. S. chorassanica induced a sub-G1 peak in the flow cytometry histogram of treated cells compared to control cells indicating that the cytotoxic mechanism is characterized by apoptosis induction. The activity of caspase-3 and 8 proteins in treated HeLa cells was significantly higher than that of the control while caspase-9 activity did not change significantly. Based on the result obtained from our study, the apoptosis pathway involved in S. chorassanica-induced cell death may be through the extrinsic pathway and it can be a novel promising candidate in the treatment of cancer

2-[4-Fluorophenyl]-N-phenylacetamide derivatives as anticancer agents: synthesis and in-vitro cytotoxicity evaluation

Cancer is a major global problem and is the second leading cause of mortality in the developed countries.Resistance to current chemotherapeutics and high incidence of adverse effects are the two principal reasons for developing new anticancer agents. Phenylacetamide derivatives can act as potential anticancer agents. Synthesis and screening of 2-[4-Fluorophenyl]-N-phenylacetamide derivatives in present study showed that these compounds act as potent anticancer agents especially against PC3[prostate carcinoma] cell line. Compounds 2a-2c with nitro moiety demonstrated a higher cytotoxic effect than compounds 2d-2f with methoxy moiety. All compounds in this series exhibited lower activity than imatinib as reference drug. Compounds 2b [IC[50] = 52 micro M] and 2c [IC[50] = 80 micro M] were the most active compounds against PC3 cell line in comparison with imatinib[IC[50] = 40 micro M]. Compound 2c [IC[50] = 100 micro M] with p-nitro substituent was the most active compound compared to imatinib[IC[50] = 98 micro M] in MCF-7 cell line

Growth inhibition and apoptosis induction of salvia chloroleuca on MCF-7 breast cancer cell line

Fragrant species of the genus Salvia have been attributed many medicinal properties, which include anticancer activity. In the present study, cytotoxic properties of total methanol extract of Salvia chloroleuca Rech. f. and Aellen and its fractions were investigated on MCF-7, a breast carcinoma cell line. Malignant and non-malignant cells were cultured in RPMI medium and incubated with different concentrations of plant extracts. Cell viability was quantitated by 3-[4,5-dimethylthiazol-2-yl] -5[3-carboxymethoxyphenyl] -2-[4-sulphophenyl] -2H-tetrazolium [MTS] assay. Apoptotic cells were determined using propidium iodide [PI] staining of DNA fragmentation by flow cytometry [sub-Gl peak]. S. chloroleuca inhibited the growth of malignant cells in a dose-dependent manner. Among solvent fractions of S. chloroleuca, the "-hexane and methylene chloride fractions were found to be more toxic compared to other fractions. S. chloroleuca-induced a sub-Gl peak in flow cytometry histogram of treated cells compared to control and DNA fragmentation suggested the induction of apoptosis. Administration of N-acetyl cysteine and vitamin C two ROS scavengers also resulted in significant inhibition of cytotoxicity induced by S. chloroleuca. These results support a mechanism whereby S. chloroleuca induces apoptosis of MCF-7 human breast cells through a ROS-mediated pathway

Cytotoxic and apoptotic potential of rheum turkestanicum janisch root extract on human cancer and normal cells

Rheum turkestanicum Janischew. [Polygonaceae] is a plant that grows in central Asia and in north-east of Iran. Traditionally, people use roots of/?, turkestanicum as an anti-diabetic and anti-hypertensive as well as anticancer agent. In this study the cytotoxicity and apoptogenic properties of ethyl acetate [EtOAc], [-hexane and H[2]O extracts from Rheum turkestanicum Janischew. [Polygonaceae] root were determined against HeLa and MCF-7 cell lines and human blood lymphocytes. Malignant and non-malignant cells were cultured in RPMI1640 medium and incubated with different concentrations of plant extracts. Cell viability was measured by MTS assay. Apoptotic cells were evaluated using PI staining of DNA fragmentation by flow cytometry [sub-G 1 peak]. The degree of DNA fragmentation was analyzed using agarose gel electrophoresis based on the formation of inter-nucleosomal units. The expression of apoptosis-related protein Bax and PARP cleavage were detected by Western blotting. EtOAc and w-hexane extracts decreased cell viability in malignant but not in non-malignant cells, as a concentration and time dependent manner. EtOAc extract induced a sub-G 1 peak in flow cytometry histogram of treated cells compared to the control. DNA fragmentation indicating apoptotic cell death was involved in R. turkestanicum induced toxicity and cleaved PARP fragment was also detected. In conclusion, this is the first report on the cytotoxic effects of R. turkestanicum in which apoptosis played an important role. However, further evaluations are needed to fully understand the possible anti-tumor properties

Protective effect of Nigella sativa and thymoquinone on serum/glucose deprivation-induced DNA damage in PC12 cells

The discovery and development of natural products with potent antioxidant properties has been one of the most interesting and promising approaches in the search for treatment of CNS injuries. The most significant consequence of the oxidative stress is thought to be the DNA modifications, which can become permanent via the formation of mutations and other types of genomic instability resulting cellular dysfunction. Serum/glucose deprivation [SGD] has served as an excellent in vitro model for the understanding of the molecular mechanisms of neuronal damage during ischemia and for the development of neuroprotective drugs against ischemia-induced brain injury. Nigella sativa [N. sativa] seeds and thymoquinone [TQ], its most abundant constituent, have been shown to possess antiinflammatory, antioxidant, chemopreventive and anti-neoplastic effects both in vitro and in vivo. Therefore, in this study we investigated genoprotective effects of N. sativa and TQ on DNA damage of PC12 cells under SGD condition. PC12 cells were cultured in DMEM medium containing 10% [v/v] fetal bovine serum, 100 units/ml penicillin, and 100 micro g/ml streptomycin. Initially cells were pretreated with different concentrations of N. sativa extract [NSE], [10, 50, 250 micro g/ml] and TQ [1, 5, 10 micro g/ml] for 6 h and then deprived of serum/glucose [SGD] for 18 h. The alkaline comet assay was used to evaluate the effect of these compounds on DNA damage following ischemic insult. The amount of DNA in the comet tail [% tail DNA] was measured as an indicator of DNA damage. A significant increase in the% tail DNA was seen in nuclei of cells following SGD induced DNA damage [p<0.001]. In the control groups, no significant difference was found in the% tail DNA between NSE- or TQ-pretreated and vehicle-pretreated PC12 cells [p>0.05]. NSE and TQ pretreatment resulted in a significant decrease in DNA damage following ischemic insult [p<0.001]. This suppression of DNA damage by NSE and TQ was found to be dose-dependent. These data indicate that NSE and TQ have a genoprotective property, as revealed by the comet assay, under SGD condition in PC12 cells

Study of cytotoxic properties of Rosa damascena extract in human cervix carcinoma cell line

Cancer is a major health problem worldwide and current therapies for cancer are often limited by short-term efficacy due to drug resistance. There has been much interest in the use of naturally occurring compounds with chemo-preventive and chemotherapeutic properties in the treatment of cancers. Rose is one of the most important groups of ornamental plants which their fruits and flowers are used in a wide variety of foods, nutritional products and different traditional medicines. In this study cytotoxic effect of Rosa damascena extract was evaluated on HeLa cell line. HeLa cells were cultured in DMEM medium and incubated with different concentrations of Rosa damascene [R. damascene] extract. Cell viability was quantitated by MTT assay. Rosa decreased cell viability in malignant cells in a concentration and time dependent manner. The IC50 values against HeLa were determined as 2135, 1540 and 305.1 micro g.ml[-1] after 24, 48 and 72h, respectively. It might be concluded that R. damascena could cause cell death in HeLa cells which could be also considered as a promising chemotherapeutic agent in cancer treatment in future

Antiviral activity of obtained extracts from different parts of Cupressus sempervirens against herpes simplex virus type 1

The aim of this study was to search for new antiviral agents from herbal medicines. Ethanol extracts of C. semipervirens, C. semipervirens var. horizontalis and C. semipervirens cv. Cereiformis were used in experiments to test their influence on herpes viruses [HSV-1]. HeLa cells monolayers were infected with herpes viruses [HSV-1]. Antiviral activity of the plant extracts assessed using Hematoxylin and Eosin method and observed under a light microscope. All tests were compared with a positive control, acyclovir. showed that all three plants have antiviral activity against HSV-1 virus. The most active extract was the obtained extract from C. semipervirens. Among the different parts of this medicinal plant tested, the fruit's extract appeared to possess the strongest anti- HSV activity. In, of the extracts tested in this survey all showed significant antiviral potency

Apoptosis: from signaling pathways to therapeutic tools

Apoptosis or programmed cell death is a gene regulated phenomenon which is important in both physiological and pathological conditions. It is characterized by distinct morphological features including chromatin condensation, cell and nuclear shrinkage, membrane blebbing and oligonucleosomal DNA fragmentation. Although, two major apoptotic pathways including 1] the death receptor [extrinsic] and 2] mitochondrial [intrinsic] pathway have been identified, recently endoplasmic reticulum and lysosomal pathways have been also recognized. Depending on both the cell type and the initiating factor, distinct pathways are activated. The pathways share a common final phase of apoptosis, consisting of activation of the executioner caspases and dismantling of substrates critical for cell survival. The important regulatory mechanisms include death receptors, caspases, mitochondria and Bcl-2 family proteins. Modulating of apoptosis is a novel therapeutic strategy in treatment of different diseases. These include situations with unwanted cell accumulation [cancer] and failure to diminish aberrant cells [autoimmune diseases] or diseases with an inappropriate cell loss [heart failure, stroke, AIDS and neurodegenerative diseases]. Modulation of apoptosis is a novel therapeutic strategy in treatment of different diseases. Many approaches including gene therapy, antisense strategies and numerous apoptotic drugs to target specific apoptotic regulators, are currently being developed. The goal of this review is to provide a general overview of current knowledge on the process of apoptosis including morphology, biochemistry, signaling as well as a discussion of apoptosis in diseases and effective therapy