Drug therapy is essential for cancer treatment. The molecular targeted anticancer drugs develop rapidly in recent years, since the effectiveness of traditional chemotherapy is unsatisfactory and the adverse reactions are high. However, molecular targeted anticancer drugs would damage the function of heart, liver or lung, and may cause adverse effects such as hand-foot syndrome, which restrains their clinical application. Therefore, it is critical for pharmaceutical toxicology to study the toxicity, the related mechanisms and the preventive measures of molecular targeted anticancer drugs.
Antineoplastic Agents ; toxicity ; Humans ; Molecular Targeted Therapy

Cortex Fraxini is a commonly used traditional Chinese medicine. It has been indicated that Cortex Fraxini possess various pharmacological effects, including anti-pathogenic microorganism, anti-inflammatory, analgesic, anti-cancer, anti-oxidative stress, neuroprotective and vascular protect effects. Cortex Fraxini has been therapeutically used in the treatment of inflammations, bacillary dysentery, relieving fever, relieving cough and asthma. This paper reviewed recent progress in the studies on pharmacological effects and clinical applications of Cortex Fraxini.
Analgesics ; pharmacology ; toxicity ; Animals ; Anti-Bacterial Agents ; pharmacology ; toxicity ; Anti-Inflammatory Agents ; pharmacology ; toxicity ; Antineoplastic Agents ; pharmacology ; toxicity ; Drugs, Chinese Herbal ; pharmacology ; toxicity ; Humans

Autophagy is a crucial biological process in eukaryotes, which is involved in cell growth, survival and energy metabolism. It has been confirmed that autophagy mediates toxicity of anticancer drugs, especially in heart, liver and neuron. It is important to understand the function and mechanism of autophagy in anticancer drugs-induced toxicity. Given that autophagy is a double-edged sword in the maintenance of the function of heart, liver and neuron, the autophagy-mediated toxicity are very complicated in the body. We provide a review on the concept of autophagy and current status about autophagy-mediated toxicity of anticancer drugs. The knowledge is crucial in the basic study of anticancer drugs-induced toxicity, and provides some strategies for the development of alleviating the toxicity of anticancer drugs.
Antineoplastic Agents ; pharmacology ; toxicity ; Autophagy ; Humans ; Neoplasms ; drug therapy

The alkaloid ecteinascidin-743, isolated from the marine tunicate Ecteinascidia turbinata, binds to DNA and induces cytotoxic effects in several tumors. The drug is being codeveloped by Pharma Mar and Ortho Biotech. In May 2001 and October 2003, it was granted orphan drug status by the European Commission for soft tissue sarcoma and ovarian cancer, respectively. This paper reviews its research progress, including chemical synthesis, in vitro studies and mechanism of action, antitumor activity in vivo, toxicity, pharmacokinetics, and clinical studies.
Animals ; Antineoplastic Agents, Alkylating ; pharmacokinetics ; pharmacology ; toxicity ; Dioxoles ; pharmacokinetics ; pharmacology ; toxicity ; Humans ; Isoquinolines ; pharmacokinetics ; pharmacology ; toxicity ; Tetrahydroisoquinolines

Spices have enjoyed a long history and a worldwide application. Of particular interest is the pharmaceutical value of spices in addition to its basic seasoning function in cooking. Concretely, equipped with complex chemical compositions, spices are of significant importance in pharmacologic actions, like antioxidant, antibacterial, antitumor, as well as therapeutical effects in gastrointestinal disorders and cardiovascular disease. Although increasing evidences in support of its distinct role in the medical field has recently reported, little information is available for substantive, thorough and sophisticated researches on its chemical constituents and pharmacological activities, especially mechanism of these actions. Therefore, in popular wave of studies directed at a single spice, this review presents systematic studies on the chemical constituents and pharmacological activities associated with common used spices, together with current typical individual studies on functional mechanism, in order to pave the way for the exploitation and development of new medicines derived from the chemical compounds of spice (such as, piperine, curcumin, geniposide, cinnamaldehyde, cinnamic acid, linalool, estragole, perillaldehyde, syringic acid, crocin).
Anti-Infective Agents ; pharmacology ; Antineoplastic Agents ; pharmacology ; Antioxidants ; pharmacology ; Cardiovascular System ; drug effects ; Digestive System ; drug effects ; Spices ; analysis ; toxicity

BACKGROUND/AIMS: Darbepoetin alfa (DPO) exhibits comparable renoprotective effects to erythropoietin (EPO) in several animal models of acute renal injury. We examined whether DPO also attenuated renal injury in a rat model of cisplatin nephrotoxicity. METHODS: Male Spague-Dawley rats were divided into four groups: untreated, DPO-treated, cisplatin-injected, and DPO-treated cisplatin-injected. DPO pretreatment was conducted 24 hours after and just before cisplatin administration. Ninety-six hours after cisplatin administration, animals in all experimental groups were sacrificed. We examined serology; real-time reverse transcription polymerase chain reaction (RT-PCR) for TNF-alpha, Bcl-2, and MCP-1 gene expression; and Western blots for caspase-3. We also conducted terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and light microscopy. RESULTS: Pretreatment with DPO significantly reduced the levels of blood urea nitrogen and serum creatinine, the magnitude of renal tubular epithelial damage, and renal gene expression of TNF-alpha, Fas, and MCP-1 in kidneys injured by cisplatin. Pretreatment with DPO significantly increased Bcl-2 mRNA levels in kidneys injured by cisplatin, and significantly reduced activated caspase-3 and TUNEL-positive cells. CONCLUSIONS: DPO exhibits a renoprotective effect in experimental cisplatin-induced renal injury, the mechanism of which may involve DPO antiinflammatory and antiapoptotic effects.
Animals ; Anti-Inflammatory Agents/pharmacology ; Antineoplastic Agents/*toxicity ; Apoptosis/drug effects ; Cisplatin/*toxicity ; Erythropoietin/*analogs & derivatives/pharmacology ; Hematocrit ; Kidney/*drug effects/pathology ; Male ; Rats ; Rats, Sprague-Dawley

Animals ; Antineoplastic Agents ; toxicity ; Cisplatin ; toxicity ; Drugs, Chinese Herbal ; pharmacology ; Hearing Loss ; chemically induced ; Male ; Mice ; Mice, Inbred Strains ; Salvia miltiorrhiza

Long circulating paclitaxel microemulsions (TXL-M) were prepared and its anticancer effect was evaluated in metronomic chemotherapy of cancer using animal tumor models. In TXL-M, paclitaxel was dissolved in vitamin E and polyethylene glycol-distearoylphosphatidylethanolamine (PEG-DSPE) was used as surfactant. The shape and particle size distribution of TXL-M were evaluated using an electronic microscope and a laser size scanner. The toxicity comparisons of TXL-M and paclitaxel were conducted using mice. Its anticancer effect and long circulation were evaluated using animal tumor model in C57BL/6 mice. The average diameter of TXL-M was (98.6 +/- 11.2) nm and its zeta potential was (-32.4 +/- 6.8) mV. Compared with paclitaxel, TXL-M showed lower toxicity. When used in metronomic chemotherapy of cancer, TXL-M showed longer circulation time in the blood and greater anticancer effect than paclitaxel. Thus, TXL-M is a better candidate for metronomic chemotherapy of cancer than paclitaxel injection.
Animals ; Antineoplastic Agents, Phytogenic ; administration & dosage ; therapeutic use ; toxicity ; Female ; Male ; Mice ; Mice, Inbred C57BL ; Paclitaxel ; administration & dosage ; therapeutic use ; toxicity ; Tumor Cells, Cultured

Animals ; Antineoplastic Agents ; toxicity ; Brain ; metabolism ; Cisplatin ; toxicity ; DNA Damage ; drug effects ; Deoxyguanosine ; analogs & derivatives ; analysis ; Female ; Kidney ; metabolism ; Male ; Mice ; Mice, Inbred ICR ; Oxidative Stress ; drug effects

AIM: To discover more active and water-soluble derivatives of tetracyclic diterpenoids containing an exo-methylene cyclopentanone or an α-methylenelactone moiety. METHODS: All of the key intermediates were synthesized from stevioside, and the target compounds were obtained through glycosylation of the 4-carboxyl group. The cytotoxicity of the target compounds against six human cancer cell lines, HepG2, Bel-7402, A549, U251, MCF-7 and MDA-MB-231, were evaluated by the MTT assay. RESULTS: Compound 1b was more effective than the positive control adriamycin against the HepG2, Bel-7402, A549, MCF-7, and MDA-MB-231 cell lines with IC50 values of 0.12, 0.91, 0.35, 0.08, and 0.07 μmol·L(-1), respectively. Moreover, compound 3c exhibited the most potent and selective cytotoxic activity against the HepG2 cell line (IC50, 0.01 μmol·L(-1)). CONCLUSION Compounds 1b and 3c could be considered as potential anticancer candidates for further study.
Antineoplastic Agents ; chemistry ; toxicity ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Diterpenes, Kaurane ; chemistry ; toxicity ; Drug Evaluation, Preclinical ; Glycosylation ; Humans ; Molecular Structure