Cell death in HeLa cells upon imperatorin and cisplatin treatment

There is growing evidence that commonly applied chemotherapy regimens can be improved by introducingnew, specific, active and low side-effect drugs, or by combining substances to obtain the required clinicaleffect. The aim of the present study was to investigate the effects of imperatorin and cisplatin, applied separatelyor in combination, on apoptosis, necrosis and autophagy induction in the human cervical carcinoma cell line(HeLa). Imperatorin appeared to be a potent autophagy inducer, rather than a necrotic or apoptotic one. Incontrast, cisplatin induced mainly apoptosis and necrosis after 6 h and 24 h, while longer incubation resultedonly in necrosis induction. When HeLa cells were incubated with both drugs, autophagy appeared most frequently,although to a smaller extent than that observed after imperatorin administered alone. At the molecularlevel, autophagy was correlated with the presence of the cleaved form of microtubule-associated protein 1 lightchain LC3 — LC3II. It was also accompanied by the inhibition of heat shock proteins Hsp27 and Hsp72 expression.Our results indicate that imperatorin alone, or in combination with cisplatin, is mainly an autopahgy inducerin HeLa cells.There is growing evidence that commonly applied chemotherapy regimens can be improved by introducingnew, specific, active and low side-effect drugs, or by combining substances to obtain the required clinicaleffect. The aim of the present study was to investigate the effects of imperatorin and cisplatin, applied separatelyor in combination, on apoptosis, necrosis and autophagy induction in the human cervical carcinoma cell line(HeLa). Imperatorin appeared to be a potent autophagy inducer, rather than a necrotic or apoptotic one. Incontrast, cisplatin induced mainly apoptosis and necrosis after 6 h and 24 h, while longer incubation resultedonly in necrosis induction. When HeLa cells were incubated with both drugs, autophagy appeared most frequently,although to a smaller extent than that observed after imperatorin administered alone. At the molecularlevel, autophagy was correlated with the presence of the cleaved form of microtubule-associated protein 1 lightchain LC3 — LC3II. It was also accompanied by the inhibition of heat shock proteins Hsp27 and Hsp72 expression.Our results indicate that imperatorin alone, or in combination with cisplatin, is mainly an autopahgy inducerin HeLa cells

Induction of cancer-specific cytotoxicity towards human prostate and skin cells using quercetin and ultrasound

Bioflavonoids, such as quercetin, have recently emerged as a new class of chemotherapeutic drugs for the treatment of various cancer types, but are marred by their low potency and poor selectivity. We report that a short application of low-frequency ultrasound selectively sensitises prostate and skin cancer cells against quercetin. Pretreatment of cells with ultrasound (20 kHz, 2 W cm−2, 60 s) selectively induced cytotoxicity in skin and prostate cancer cells, while having minimal effect on corresponding normal cell lines. About 90% of the viable skin cancer cell population was lost within 48 h after ultrasound-quercetin (50 μM) treatment. Ultrasound reduced the LC50 of quercetin for skin cancer cells by almost 80-fold, while showing no effect on LC50 for nonmalignant skin cells

Small molecule sensitization to TRAIL is mediated via nuclear localization, phosphorylation and inhibition of chaperone activity of Hsp27

10.1038/cddis.2013.413Cell Death and Disease410

MRSI-based molecular imaging of therapy response to temozolomide in preclinical glioblastoma using source analysis

Characterization of Gliobastoma (GB) response to treatment is a key factor for improving patient's survival and prognosis. Magnetic resonance Imaging and Spectroscopic Imaging (MRI/MRSI) provide morphologic and metabolic profiles of GB but usually fail to produce unequivocal biomarkers of response. The purpose of this work is to provide proof-of-concept of the capability of a semi-supervised signal source extraction methodology to produce images with robust recognition of response to temozolomide (TMZ) in a preclinical GB model

Hepatocyte growth factor (HGF), heat shock proteins (HSPs) and multidrug resistance protein (MRP) expression in co-culture of colon tumor spheroids with normal cells after incubation with interleukin-1<img src='/image/spc_char/beta.gif' border=0> (IL-1<img src='/image/spc_char/beta.gif' border=0>) and/or camptothecin (CPT-11)

354-364Tumor chemoresistance and metastasis are some of the most important problems in colon cancer therapy. In the present study, co-cultures of human colon carcinoma cell spheroids, obtained from different grades of tumor, with human colon epithelium, myofibroblast and endothelial cell monolayers were performed. The purpose of these co-cultures was to reflect, in in vitro conditions, different stages of colon tumor development. In order to investigate the invasive capacities of the tumor cells and their resistance to chemotherapy, HGF, HSP27, HSP72 and MRP levels were analyzed after incubation of the co-cultures with IL-1 and irinotecan (CPT-11) added as single agents or in combination. Myofibroblasts produced significantly higher amounts of HGF than epithelial cells. Tumor cells released trace amounts of this molecule. In co-cultures, IL-1 induced HGF release, while CPT-11 alone or combined with IL-1decreased HGF secretion. An immunoblotting analysis followed by densitometry revealed that the combination of IL-1 plus CPT-11 added to the co-cultures led to a decrease in HSPs and MRP levels. In conclusion, direct and paracrine interactions of colon tumor cell spheroids with normal cells and exogenously added CPT-11 change HSP27, HSP72 and MRP expression in comparison to monocultures. IL-1 and CPT-11, dependent on whether they are added separately or jointly, differentially modulate HGF expression in monocultures of colon tumor spheroids or normal cells and their co-cultures

Essential Oil from Arnica Montana L. Achenes: Chemical Characteristics and Anticancer Activity

Mountain arnica Arnica montana L. is a source of several metabolite classes with diverse biological activities. The chemical composition of essential oil and its major volatile components in arnica may vary depending on the geographical region, environmental factors, and plant organ. The objective of this study was to characterize the chemical composition of essential oil derived from A. montana achenes and to investigate its effect on induction of apoptosis and autophagy in human anaplastic astrocytoma MOGGCCM and glioblastoma multiforme T98G cell lines. The chemical composition of essential oil extracted from the achenes was examined with the use of Gas Chromatography&ndash;Mass Spectrometry GC-MS. Only 16 components of the essential oil obtained from the achenes of 3-year-old plants and 18 components in the essential oil obtained from the achenes of 4-year-old plants constituted ca. 94.14% and 96.38% of the total EO content, respectively. The main components in the EO from the arnica achenes were 2,5-dimethoxy-p-cymene (39.54 and 44.65%), cumene (13.24 and 10.71%), thymol methyl ether (8.66 and 8.63%), 2,6-diisopropylanisole (8.55 and 8.41%), decanal (7.31 and 6.28%), and 1,2,2,3-tetramethylcyclopent-3-enol (4.33 and 2.94%) in the 3- and 4-year-old plants, respectively. The essential oils were found to exert an anticancer effect by induction of cell death in anaplastic astrocytoma and glioblastoma multiforme cells. The induction of apoptosis at a level of 25.7&ndash;32.7% facilitates the use of this secondary metabolite in further studies focused on the development of glioma therapy in the future. Probably, this component plays a key role in the anticancer activity against the MOGGCCM and T98G cell lines. The present study is the first report on the composition and anticancer activities of essential oil from A. montana achenes, and further studies are required to explore its potential for future medicinal purposes

Quercetin suppresses heat shock-induced nuclear translocation of Hsp72

The effect of quercetin and heat shock on the Hsp72 level and distribution in HeLa cells was studied by Western blotting, indirect immunofluorescence and immunogold electron microscopy. In control cells and after quercetin treatment, Hsp72 was located both in the cytoplasm and in the nucleus in comparable amounts. After hyperthermia, the level of nuclear Hsp72 raised dramatically. Expression of Hsp72 in cytoplasm was also higher but not to such extent as that observed in the nucleus. Preincubation of heated cells with quercetin inhibited strong Hsp72 expression observed after hyperthermia and changed the intracellular Hsp72 distribution. The cytoplasmic level of protein exceeded the nuclear one, especially around the nucleus, where the coat of Hsp72 was noticed. Observations indicating that quercetin was present around and in the nuclear envelope suggested an involvement of this drug in the inhibition of nuclear translocation. Our results indicate that pro-apoptotic activity of quercetin may be correlated not only with the inhibition of Hsp72 expression but also with suppression of its migration to the nucleus