Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.22.56 (caspase-3)
 35,750 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Valproic acid (VPA) is an established drug in the long-term therapy of seizure disorders. Recently, VPA has been associated with anticancer activity, an effect thought to be mediated through the inhibition of cellular histone deacetylase 1. We investigated the effect of various doses of VPA (0, 1.2, and 5.0 mmol/L) administered either acutely or chronically on histone acetylation, p21 gene expression, androgen receptor expression, prostate-specific antigen (PSA) expression, and cell survival and proliferation in prostate cancer cell lines. We also studied the effect of chronic VPA on tumor xenograft growth in vivo. Our results show that acute treatment (3 days) VPA can increase net histone H3 acetylation and up-regulate p21, AR, and cytosolic PSA expression. Interestingly, the effects on AR and PSA are reversed with chronic treatment. In addition, acute VPA reduces cell survival but has no effect on the subsequent proliferation of surviving cells following drug withdrawal. However, when VPA is chronically administered (10-14 days) to prostate cancer cells, even lower doses of VPA result in marked decreases in the net proliferation rate, correlating with increased caspase-2 and caspase-3 activation. These effects are evident in both androgen receptor-positive (LNCaP and C4-2) and androgen receptor-negative (DU145 and PC3) prostate cancer cells. Moreover, chronic VPA treatment results in statistically significant reduction of tumor xenograft growth in vivo. We conclude that acute treatment has nominal effects on prostate cancer cell survival and proliferation, but chronic VPA results in profound decreases in proliferation, independently of androgen regulation.
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PMID:Chronic administration of valproic acid inhibits prostate cancer cell growth in vitro and in vivo. 1684 72

In spite of compelling evidence-implicating caspases in drug-induced apoptosis, how tumors modulate caspase expression and activity to overcome the cytotoxicity of anticancer agents is not fully understood. To address this issue, we investigated the role of caspases-3 and caspase-7 in determining the response of breast and lung tumor cell lines to chemotherapy. We found that an early and late apoptotic response correlated with weak and strong cellular caspase-activation, respectively. The results highlight an underappreciated relationship of temporal apoptotic response with caspase-activation and drug resistance. Moreover, the extent of tumor growth restoration after drug withdrawal was dependent on the degree of endogenous blockage of caspase-3 and caspase-7 cleavages. This points to an unrecognized role of caspase modulation in tumor recurrence and suggests that targeting caspase cleavage is a rational approach to increasing potency of cancer drugs.
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PMID:Modulation of effector caspase cleavage determines response of breast and lung tumor cell lines to chemotherapy. 1924 Nov 92

Ketamine is increasingly used in clinical practice, and ketamine addiction is common in young individuals. There are limited reviews on the chronic effects of ketamine on the testes. Three groups of rats received saline or ketamine 50 mg/kg/day intraperitoneally for 6 weeks with or without a subsequent 4-week drug-free period. Serum follicle-stimulating hormone, luteinizing hormone, prolactin, and testosterone levels, as well as testicular malondialdehyde concentrations, were measured. Epididymal sperm parameters were assessed. Testicular tissues were examined by hematoxylin and eosin staining and immunohistochemical staining using caspase-3 and vimentin antibodies. Chronic ketamine injection significantly decreased the levels of the examined hormones and adversely affected sperm parameters. Testicular tissue showed a significant increase in caspase-3 expression. In addition, Sertoli cell shape and position were disrupted. These effects disappeared 4 weeks after drug withdrawal. Chronic ketamine treatment has revisable hazardous effects on the rat reproductive function. There is a need to increase the knowledge of physicians and the public regarding these harmful effects of ketamine.
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PMID:Toxicity and postwithdrawal effects of ketamine on the reproductive function of male albino rats: Hormonal, histological, and immunohistochemical study. 3215 15