Antimitotic effects

In addition, the alkaloid colchicine (from Colchicum autumnale) blocks tubulin polymerization by binding to heterodimeric (3-tubulin between amino acids 239 and 254. Since it inhibits the MT-dependent migration of granulocytes into areas of inflammation and their MT-dependent release of proinflammatory agents, it is used to treat attacks of gout. Its antimitotic effect in the gastrointestinal system induces diarrhoea. Nocodazole competes for the binding site of colchicine and has similar effects on heterodimeric (3-tubulin. 

Dividing cells in culture exposed to vinblastine or vincristine are arrested from further growth during mitosis (12,13). In fact, the antimitotic effects of this class of compounds is ubiquitous. These effects are observed at relatively low concentrations (<1 iM), and are reversible when drug is removed from the media prior to lysis of the arrested cells. The concentration of drug required to elicit an antimitotic effect is usually comparable to that required to produce a cytotoxic effect in the same cell type (14,15). Originally, this type of analysis was exceedingly laborious, but the introduction of laser- and computer-based fluoresence activated cell sorters (FACS) has rendered this type of analysis routine. Nevertheless, a cytotoxic, non-cell cycle-specific bisindole alkaloid has yet to be discovered. 

Nausea, vomiting, diarrhea, and abdominal pain are the most common side effects which result from the antimitotic effects of colchicine on the gastrointestinal mucosal cells. They can also be the forebode of serious overdose. 

One of the principles of the use of hormones in oncology is based on the fact that the growth of tumors which occur in hormone-sensitive tissues may be inhibited by hormones with opposing actions, by hormone antagonists, or by agents that inhibit the synthesis of the stimulatory hormone. Other hormone treatments are based on less specific antimitotic effects. 

The remarkable efficacy of topical corticosteroids in the treatment of inflammatory dermatoses was noted soon after the introduction of hydrocortisone in 1952. Numerous analogs are now available that offer extensive choices of potencies, concentrations, and vehicles. The therapeutic effectiveness of topical corticosteroids is based primarily on their antiinflammatory activity. Definitive explanations of the effects of corticosteroids on endogenous mediators of inflammation await further experimental clarification. The antimitotic effects of corticosteroids on human epidermis may account for an additional mechanism of action in psoriasis and other dermatologic diseases associated with increased cell turnover. The general pharmacology of these endocrine agents is discussed in Chapter 39. 

Narciclasine (215) is an antitumor agent which exerts an antimitotic effect during metaphase by immediately terminating protein synthesis in eukaryotic cells at the step of peptide bond formation (97,101,141,142), apparently by interaction with the ansiomycin area of the ribosomal peptidyl transferase center (142). The alkaloid has also been found to inhibit HeLa cell growth and to stabilize HeLa cell polysomes in vivo (97). Although DNA synthesis was retarded by narciclasine, RNA synthesis was practically unaffected (97,142). Sev-... 

Overall, quite similar antimitotic effects are observed for several constitutionally diverse natural products. There seems to be evidence for different core structures presenting a common pharmacophore. This knowledge of the spatial and functional needs of the pharmacophore should in future hopefully result in new and easy accessible derivatives with high potency, more limited side effects, and lower resistance than the natural products. 

Somatostatin Somatotropin release inhibiting factor (SRIF) displays antimitotic effects regarding various non-endocrine tumours. In animal experiments, octreotide retards tumour growth. The subcutaneous administration of octreotide (250 gg, 2x/day) resulted in a considerable improvement in survival time and quality of life. (93) There are still no clinical results available regarding the use of lanreotide, which has a longer action time. 

Pyrithione zinc s action is thought to be due to a non-specific toxicity for epidermal cells selenium sulphide is believed to have a direct antimitotic effect. 

Knecht, A. and Humpf, H. U. 2006. Cytotoxic and antimitotic effects of N-containing Monascus metabolites studied using immortalized human kidney epithelial cells. Mol. Nutr. Food Res. 50(4-5), 406-412. 

The PAs are not toxic until they are metabolized in the liver. Dehydro genation by P-450 enzymes forms toxic pyrrolic metabolites. These pyrrolic metabolites either undergo hydrolysis to pyrrolic alcohols or destroy surrounding tissues. Both the pyrrolic esters (primary metabolites) and the pyrrolic alcohols (secondary metabolites) have antimitotic effects and are responsible for the damage to cells in the liver (Abbott, 1988). 

In summary, though they act via distinct pathways, immunophilins may be considered as presenter proteins whose activity is conditioned by the nature of the effector interacting at their active site. However, CsA- and FK506-related compounds have additional properties such as neurotrophic, cardioprotective, and antimitotic effects [32] which are not yet completely understood. 

Various drugs, Including colchicine and taxol, disrupt microtubule dynamics and have an antimitotic effect. Some of these drugs are useful In the treatment of certain cancers. 

Research work on the mode of action of these compounds furnished the theoretical basis for the chemical control of insects by means of chemosterilants, and most of the compounds showing such action were first described as antitumour agents. In no other field is the interaction between plant protection and human therapy so close as that between the chemotherapy of cancer and insect control by chemosterilants. The capacity of these substances to interfere with the biosynthesis of DNA served as the common theoretical basis. In addition to other effects such as antitumour and antimitotic effects, deactivation of viruses, etc., a characteristic outcome of this interference is the mutagenic effect and, closely related to this, inhibition of reproduction (Bofkovec, 1962). 

Colchicine exerts a variety of pharmacological effects, but how these occur or how they relate to its activity in gout is not well understood. It has antimitotic effects, arresting cell division in G1 by interfering with microtubule and spindle formation (an effect shared with vinca alkaloids). This... 

The demonstrated susceptibility differences between kinetoplastid and mammalian tubulin make this protein not only an attractive but also a feasible taiget for antikinetoplastid compounds. Oryzalin derivatives GB-II-5 (7), GB-II-150 (12), andTG-II-36 (19) are promising lead compounds showing potent and selective antimitotic effects against kinetoplastid parasites. The development of a model for the dinitroaniline binding site on leishmanial tubulin would permit the application of structure-based dn discovery techniques in order to identify... 

These enzyme-inducing antiepileptics increase the metabolism of vincristine by the cytochrome P450 isoenzyme CYTBA4. However, in vitro studies have shown that phenytoin may potentiate the antineoplastic (antimitotic) effects of the vinca alkaloids. Thus, further study is required to determine the overall effect of phenytoin on the efficacy and toxicity of vincristine and other vinca alkaloids. Carbamazepine would be expected to reduce the efficacy of vincristine. 

Activity Many F. induce a brown pigmentation in the skin on exposure to sunlight. They are photosensitizing, phototoxic, and can induce allergic dermatitis (Berloque s dermatitis), possibly with severe symptoms such as blister formation. The effect can also arise when, for example, scented toilet waters whose plant components still contain F. are applied to the skin. Use In photochemotherapy for vitiligo, psoriasis, atopic dermatitis, mycosis togoides. Photoactivated F. bind covalently as haptens to proteins as well as pyrimidines of DNA and thus have antimitotic effects. For synthesis, see Lit.. ... 

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