OBJECTIVETo investigate whether paclitaxel (Taxel) can efficiently induce apoptosis of ACC-2 or not, and to study the relation of apoptosis and arrest of cell mitosis.

METHODSPaclitaxel-induced arrest of cell mitosis and apoptosis of ACC-2 cells in various concentration and different treat time were determined using transmission electron microscope (TEM), fluorescence microscope, flow-cytometry and DNA agarose gel electrophoresis technique.

RESULTSUnder fluorescence microscope, apoptotic cells were green with irregular clumping of nucleus chromatin, or even nuclear chromatin segregation. The typical ultra-structural changes of apoptosis observed by TEM were cell compaction, margination of nuclear chromatin, condensation of cytoplasm, protuberances and apoptotic body. "DNA Ladder" was absent in agarose gel electrophoresis of DNA extracted from culture of ACC-2 cells and paclitaxel-induced ACC-2 cells. "Sub-G(1)" phase peak of ACC-2 cells induced by 50 nmol/L paclitaxel in 48 h and 72 h was 17.13% and 16.26%, respectively. The percentage of G(2)/M phase increased in accordance with raise of the paclitaxel concentration and prolongation of treatment. The typical ultra-structural changes of apoptosis were observed in case that G(2)/M phase was arrested.

CONCLUSIONSPaclitaxel could induce apoptosis of ACC-2 cells. Arrest of G(2)/M phase might induce apoptosis of ACC-2 cells.

Apoptosis ; drug effects ; Carcinoma, Adenoid Cystic ; pathology ; ultrastructure ; Dose-Response Relationship, Drug ; G2 Phase ; drug effects ; Humans ; Mitosis ; drug effects ; Paclitaxel ; pharmacology ; Tumor Cells, Cultured

There is evidence from other studies that some degree of cartilage healing may take place after the initiation of an inflammatory response. It is postulated that the induction of the platelet-cartilage interaction may eventuate in cartilage repair. The treatment of fresh articular cartilage with proteolytic enzymes rendered the tissue active as a platelet aggregant. During platelet aggregation a host of active substances are released which are known to play a role in the inflammatory response (Thompson 1975). This study was undertaken to evaluate the effects of trypsin on the surface injury of rabbit hyaline cartilage. The results were as follows: 1) Hyaline cell regeneration was observed only in the group treated with trypsin and blood; 2) Hyaline cartilage regeneration did not occur in the group treated with a single injection of trypsin or blood; 3) There was no significant damage to the healthy articular cartilage by the single injection of trypsin or blood, or both; and 4) Platelets do not adhere to cartilage and superficial damaged cartilage does not induce platelet aggregation.
Animal ; Cartilage, Articular/*drug effects/physiology/ultrastructure ; Cell Division ; Mitosis/physiology ; Platelet Aggregation/drug effects ; Rabbits ; Regeneration ; Trypsin/*pharmacology ; Wound Healing/drug effects/physiology

Treatment with certain DNA-damaging agents induce a complex cellular response comprising pertubation of cell cycle progression and/or apoptosis on proliferating mammalian cells. Our studies were focused on the cellular effects of nickel (II) acetate, DNA-damaging agent, on Chinese hamster ovary (CHO) cells. Fragmented DNAs were examined by agarose gel electrophoresis and cell cycle was determined by DNA flow cytometry using propidium iodide fluorescence. Apparent DNA laddering was observed in cells treated with 240 microM nickel (II) and increased with a concentration-dependent manner. Treatment of nickel (II) acetate resulted in apoptosis which was accompanied by G2/M cell accumulation. Proportion of CHO cells in G2/M phase was also significantly increased in cells exposed to at least 480 microM nickel (II) from 57.7% of cells in the G0/G1 phase, 34.7% in the S phase, and 7.6% in the G2/M1 phase for 0 microM nickel (II), to 58.6%, 14.5%, and 26.9% for 640 microM nickel (II). These findings suggest that nickel (II) can modulate cellular response through some common effectors involving in both apoptotic and cell cycle regulatory pathways.
Animal ; Apoptosis/drug effects* ; CHO Cells/drug effects* ; CHO Cells/cytology ; Cell Cycle/drug effects* ; DNA Fragmentation/drug effects ; Flow Cytometry ; G2 Phase/drug effects ; Hamsters ; Mitosis/drug effects ; Nickel/pharmacology*

Experimental data suggest that Resveratrol, a compound found in grapes and other fruits may influence cell proliferation and apoptosis. The aim of our experiments was to study the effect of Resveratrol on tumor cell cultures and an endothelial cell culture in order to examine the effect of various doses of this compound on active cell death and cell proliferation. Human tumor (HT-29, SW-620, HT-1080) and endothelial (HUV-EC-C) cells were treated with various doses of (0.1 to 100.0 microg/ml) Resveratrol in vitro. Cell number, apoptotic and mitotic index was measured 24, 48 and 72 h after treatment. Low doses (0.1-1.0 microg/ml) of Resveratrol enhance cell proliferation, higher doses (10.0-100.0 microg/ml) induce apoptosis and decrease mitotic activity, which is reflected in changes of cell number. Resveratrol influences dose dependently the proliferative and apoptotic activity of human tumor and endothelial cells. The possible role of formaldehyde in the mechanism of action of Resveratrol is discussed.
Antineoplastic Agents, Phytogenic/pharmacology* ; Apoptosis* ; Cells, Cultured ; Dose-Response Relationship, Drug ; Endothelium/drug effects* ; Endothelium/cytology ; Human ; Mitosis/drug effects* ; Stilbenes/pharmacology* ; Tumor Cells, Cultured

BACKGROUNDMutations in mitotic checkpoint genes have been detected in several human cancers, which exhibit chromosome instability. We wanted to know whether mutation of hBub1 could occur in transformed human embryo lung fibroblasts (HELF) cells induced by a chemical carcinogen.

METHODSHELF cells were transformed by N-methyl-N'-nitro-N-nitrosoguaridine (MNNG), and three flasks of transformed HELF cells (named as T1, T2, and T3) were selected as amplifiers, and mutations of hBub1 in these transformed cells were analyzed by PCR-SSCP and sequencing.

RESULTSIt was found that any one of three transformed cell lines exhibited aneuploidy with a low mitotic checkpoint function. Subsequent PCR-SSCP and sequence analysis showed an AGT to CGT or ATT mutation at codon 80 in hBub1 gene in T1 cells with a resultant change in amino acid sequence.

CONCLUSIONOur study demonstrated that the mitotic checkpoint genes could be targets of MNNG.

Cell Line, Transformed ; Chromosome Aberrations ; Down-Regulation ; Fibroblasts ; drug effects ; Humans ; Lung ; cytology ; Methylnitronitrosoguanidine ; toxicity ; Mitosis ; drug effects ; Mutation ; Protein Kinases ; genetics ; Protein-Serine-Threonine Kinases

OBJECTIVETo investigate the molecular mechanisms of Z-ajoene mitosis blocking and telomerase inhibitory effects on HL-60 cells.

METHODSProliferation inhibition of HL-60 cell line was evaluated by MTT assay. Z-ajoene-induced mitotic blocking effect was investigated by flow cytometry. Immunoblotting analysis was used to determine cell cycle regulatory proteins. The telomerase activity of HL-60 cells was detected by TRAP-silver stain assay. Telomerase hTRT and TP1 mRNA level were determined by RT-PCR.

RESULTSZ-ajoene displayed great proliferation inhibiting effect on HL-60 cells. Progressive increase in the percentage of mitotic block at G(2)/M phase was observed from 4 h to 12 h after treatment with 10 micromol/L Z-ajoene, with a peak at 10 h, which was 1.95 times higher than that in control. Z-ajoene also caused an increase in cyclin B1 accumulation and a decrease of p34(cdc2) expression. But Z-ajoene did not change the level of cyclin A. After treating with 10 micromol/L Z-ajoene for 24 h, the telomerase activity of HL-60 cells was also decreased in a dose-independent manner. Furthermore, telomerase hTRT and TP1 mRNA levels decreased after 10 micromol/L Z-ajoene treatment for 24 h.

CONCLUSIONThe results suggest that Z-ajoene has potent anti-cancer activity, and that its inhibitory effect on telomerase activity and on cell growth might be the result of G(2)/M phase blocking.

Antineoplastic Agents, Phytogenic ; pharmacology ; Cell Cycle ; drug effects ; Disulfides ; pharmacology ; Garlic ; chemistry ; HL-60 Cells ; Humans ; Mitosis ; drug effects ; Telomerase ; metabolism

In the present study, 13 clinical cases of canine mammary adenocarcinoma were evaluated in order to understand the effect of Tarantula cubensis extract (TCE) on tumor tissue. Punch biopsies were taken from the tumors before treatment with TCE. Subcutaneous injections of TCE were administered three times at weekly intervals (3 mL per dog). Between days 7 and 10 after the third injection, the tumor masses were extirpated by complete unilateral mastectomy. Pre- and post-treatment tumor tissues were immunohistochemically assessed. The expression of B-cell lymphoma 2 (Bcl-2) was found to be higher in pre-treatment compared to post-treatment tissues (p < 0.01) whereas Ki-67 expression was lower in post-treatment tissues (p < 0.01). No significant differences in fibroblast growth factor or vascular endothelial growth factor expression were observed between pre- and post-treatment tissues (p > 0.05). The apoptotic index was determined to be low before treatment and increased during treatment. These results suggest that TCE may be effective for controlling the local growth of canine mammary adenocarcinoma by regulating apoptosis.
Adenocarcinoma/*drug therapy/physiopathology ; Animals ; Apoptosis/drug effects ; Dog Diseases/*drug therapy/physiopathology ; Dogs ; Female ; Mammary Neoplasms, Animal/*drug therapy/physiopathology ; Mammary Neoplasms, Experimental/*drug therapy/physiopathology ; Mitosis/drug effects ; Spiders/*chemistry

Pin1 is a phosphorylation-dependent peptidyl-prolyl cis/trans isomerase, which specifically catalyzes the amide bond isomerization of phosphoserine-proline or phosphothreonine-proline in mitotic phosphoproteins. Pin1 induces the conformational changes to control the function of phosphoproteins. Depletion of Pinl on various human cancer cell lines cause mitotic arrest and apoptosis. Pin1 is an attracting therapeutic target for anticancer and its inhibitors might be potential anticancer drug. In this review, Pin1 inhibitors and the catalytic mechanism, the biological function of Pin1 and its role in oncogenesis are summarized.
Apoptosis ; Enzyme Inhibitors ; chemical synthesis ; pharmacology ; Humans ; Mitosis ; drug effects ; NIMA-Interacting Peptidylprolyl Isomerase ; Neoplasms ; enzymology ; Peptidylprolyl Isomerase ; antagonists & inhibitors ; metabolism ; Phosphoproteins ; chemistry ; metabolism ; Phosphorylation ; drug effects ; Signal Transduction ; drug effects

OBJECTIVETo apply conidia of Pyricularia Oryzae to the screening of antimitotic constituents from marine animal sea hare.

METHODTo extract and fractionate active portions from sea hare through detecting deformation of mycelia germinated from conidia of P. Oryzae P-2b, in comparison with the cytotoxic test results in vitro.

RESULTTwo active portions, of which IC50 against P388 and HL-60 was 23.4, 18.6 and 19.4, 12.5 micrograms.ml-1, respectively, were screened from this animal.

CONCLUSIONThis bioassay method was efficiently applied to the primary screening of antimitotic portions from marine animals for the first time. Being convenient, speedy and cheap, the screening model is suitable for the bioassay of active constituents from marine life.

Animals ; Antineoplastic Agents ; isolation & purification ; pharmacology ; Aplysia ; chemistry ; HL-60 Cells ; drug effects ; Humans ; Leukemia P388 ; pathology ; Materia Medica ; isolation & purification ; pharmacology ; Mice ; Mitosis ; drug effects ; Mitosporic Fungi ; physiology ; Tumor Cells, Cultured ; drug effects

Microtubule is one of the key components of the cytoskeleton and plays an important role in the maintenance of cell shape and the process of signal transduction and mitosis. Due to the extreme importance of microtubule in the process of mitosis, tubulin becomes one of the most important targets for development of new anticancer drugs and tubulin inhibitors are used for the treatment of cancer nowadays. These inhibitors have antitumor activity by inhibiting or promoting the assembly of tubulin to microtubules and interfering the process of cell mitosis. This review summarized the research progress of the tubulin inhibitors, especially the introduction of the tubulin inhibitors of pharmacological activities and the progress of clinical research. Also, the development trend of these inhibitors is discussed.
Antineoplastic Agents ; chemical synthesis ; chemistry ; pharmacology ; Humans ; Microtubules ; drug effects ; metabolism ; Mitosis ; drug effects ; Molecular Structure ; Neoplasms ; drug therapy ; Stilbenes ; chemical synthesis ; chemistry ; pharmacology ; Structure-Activity Relationship ; Tubulin ; metabolism ; Tubulin Modulators ; chemical synthesis ; chemistry ; pharmacology