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Apoptotic Potential (apoptotic + potential)

Distribution by Scientific Domains
Medical Sciences60%
Life Sciences40%

Selected Abstracts

Regulation of signaling pathways involved in lupeol induced inhibition of proliferation and induction of apoptosis in human prostate cancer cells

MOLECULAR CARCINOGENESIS, Issue 12 2008
Sahdeo Prasad
Abstract Prostate cancer (PCa) is the most frequently diagnosed noncutaneous cancer and the leading cause of cancer related deaths in men in the United States and many other Asian countries. Dietary factors are considered as a strategic agent to control the risk of PCa. Lupeol, a triterpene, present in fruits and medicinal plants, has been shown to possess many pharmacological properties including anticancer effects. Here, effect of lupeol on cell proliferation and cell death was evaluated using human PCa cells, PC-3. In MTT assay, lupeol inhibited the cell proliferation (12,71%) in dose (50,800 µM) and time dependent manner. Flow-cytometric analysis of cell-cycle revealed that an antiproliferative effect of lupeol (400,600 µM) is associated with an increase in G2/M-phase arrest (34,58%). RT-PCR analysis showed that lupeol-induced G2/M-phase arrest was mediated through the inhibition of cyclin regulated signaling pathway. Lupeol inhibited the expression of cyclin B, cdc25C, and plk1 but induced the expression of 14-3-3, genes. However no changes were observed in the expression of gadd45, p21waf1/cip1 and cdc2 genes. Results of western blot showed that lupeol regulates the phosphorylation of cdc2 (Tyr15) and cdc25C (Ser198). Further, on increase of lupeol exposure to PC-3 cells an induction of apoptosis was recorded, which was associated with upregulation of bax, caspase-3, -9, and apaf1 genes and down regulation of antiapoptotic bcl-2 gene. The role of caspase-induced apoptosis was confirmed by increase in reactive oxygen species, loss of mitochondrial membrane potential followed by DNA fragmentation. Thus, our study suggests that lupeol possess novel antiproliferative and apoptotic potential against PCa. © 2008 Wiley-Liss, Inc. [source]

Cytotoxic and antimitotic effects of N -containing Monascus metabolites studied using immortalized human kidney epithelial cells

MOLECULAR NUTRITION & FOOD RESEARCH (FORMERLY NAHRUNG/FOOD), Issue 4-5 2006
Anja Knecht
Abstract Recently the first Monascus metabolites with a pyridine ring were detected, the monascopyridines A and B. They are formally dehydrogenated derivatives of the red rice pigments rubropunctamine and monascorubramine. Because of their structural similarity, the toxicological effects of these secondary metabolites were studied using immortalized human kidney epithelial cells. The cytotoxicity was determined with the following different endpoint detection methods: metabolic activity, trypan blue exclusion, and electronic cell counting. The compounds led to EC50 values between 11 and 31 ,mol/L but the pigments caused a stronger reduction of the cell viability. Also, the apoptotic potential was examined by measuring caspase 3 activity and detecting apoptotic bodies, but none of the tested compounds induced apoptosis. All four substances caused a rise of the mitotic index to about 9% (100 ,mol/L monascopyridine A and B) and 20% (25 ,mol/L rubropunctamine and monascorubramine). The significant decrease of the ratio of cells in the ana- and telophase to cells in the prometa- and metaphase proved a stop of the mitosis at the meta- to anaphase control point. The compounds caused mitotic arrest and the formation of structural damages like c-mitosis through interaction with the mitotic spindle. These effects point to an aneuploidy inducing potential, which is linked to cancer formation. [source]

Increased apoptotic potential and dose-enhancing effect of gold nanoparticles in combination with single-dose clinical electron beams on tumor-bearing mice

CANCER SCIENCE, Issue 7 2008
Meng-Ya Chang
High atomic number material, such as gold, may be used in conjunction with radiation to provide dose enhancement in tumors. In the current study, we investigated the dose-enhancing effect and apoptotic potential of gold nanoparticles in combination with single-dose clinical electron beams on B16F10 melanoma tumor-bearing mice. We revealed that the accumulation of gold nanoparticles was detected inside B16F10 culture cells after 18 h of incubation, and moreover, the gold nanoparticles were shown to be colocalized with endoplasmic reticulum and Golgi apparatus in cells. Furthermore, gold nanoparticles radiosensitized melanoma cells in the colony formation assay (P = 0.02). Using a B16F10 tumor-bearing mouse model, we further demonstrated that gold nanoparticles in conjunction with ionizing radiation significantly retarded tumor growth and prolonged survival compared to the radiation alone controls (P < 0.05). Importantly, an increase of apoptotic signals was detected inside tumors in the combined treatment group (P < 0.05). Knowing that radiation-induced apoptosis has been considered a determinant of tumor responses to radiation therapy, and the length of tumor regrowth delay correlated with the extent of apoptosis after single-dose radiotherapy, these results may suggest the clinical potential of gold nanoparticles in improving the outcome of melanoma radiotherapy. (Cancer Sci 2008; 99: 1479,1484) [source]

3- O -Methylfunicone, a secondary metabolite produced by Penicillium pinophilum, induces growth arrest and apoptosis in HeLa cells

CELL PROLIFERATION, Issue 6 2004
E. Buommino
The aim of this study was to investigate the mechanisms by which such properties are exerted, with special reference to any anti-proliferative and apoptotic potential, on HeLa cells. OMF treatment caused about 44% inhibition of cell growth after 24 h, and modifications in the tubulin fibre organization. In addition, a significant increase in p21 mRNA expression and a decrease in cyclin D1 and Cdk4 mRNA expression resulted at the same time. Apoptosis induction was demonstrated by the annexin V assay, cytofluorimetric analysis of the DNA content of the sub-G1 fraction and DNA laddering. Taken together, our data showed that the compound inhibits proliferation of HeLa cells by several mechanisms, such as disruption of tubulin fibres, cell cycle arrest and apoptosis induction. The capacity of the compound to affect the cell cycle and to modulate apoptosis is indicative of a potential for the development of a new agent for cancer chemotherapy. [source]