Halofantrine is a newer antimalarial drug which has not been approved for clinical use in Papua New Guinea. We assessed 21 Central Province isolates of Plasmodium falciparum for their in vitro susceptibility to halofantrine. The concentration required to inhibit 50% of parasite growth (IC50) ranged from 0.05 to 7.0 nM with a mean of 1.90 nM and a median of 1.50 nM. The minimum inhibitory concentration (MIC) values ranged from 2.5 to 50 nM with a median of 5.0 nM. All but one isolate had an MIC of 10 nM or less. These results indicate that halofantrine would be a suitable alternative for the treatment of P. falciparum malaria in the region in the future, if and when the need arises, provided that its use was carefully monitored. PIP: Halofantrine is a newer antimalarial drug which has not been approved for clinical use in Papua New Guinea. The authors assessed 21 Central Province isolates of Plasmodium falciparum for their in vitro susceptibility to halofantrine. The concentration required to inhibit 50% of parasite growth (IC50) ranged from 0.05 to 7.0 nmol with a mean of 1.90 nmol and a median of 1.50 nmol. The minimum inhibitory concentration (MIC) values ranged from 2.5 to 50 nmol with a median of 5.0 nmol. All but one isolate had an MIC of 10 nmol or less. These results indicate that halofantrine would be a suitable alternative for the treatment of P. falciparum malaria in the region in the future, if and when the need arises, provided that its use was carefully monitored.
Antimalarials - pharmacology ; In Vitro Techniques ; Microbial Sensitivity Tests ; Papua New Guinea ; Phenanthrenes - pharmacology

Objective To observe the effect of cryptotanshinone on the ferroptosis of human liver cancer HepG2 cells. Methods The viability of the HepG2 cells cultured
Ferroptosis ; Hep G2 Cells ; Humans ; Liver Neoplasms ; Phenanthrenes/pharmacology* ; Reactive Oxygen Species

Overtaking lung cancer,breast cancer is now the most commonly diagnosed cancer seriously threatening people's health and life. As the main effective component of Tripterygium wilfordii,triptolide( TP) has attracted increasing attention due to its multitarget and multi-pathway anti-tumor activity. Recent studies have revealed that breast cancer-sensitive TP enables the inactivation of breast cancer cells by inducing tumor cell apoptosis and autophagy,interfering in tumor cell metastasis,resisting drug resistance,arresting tumor cell cycle,and influencing tumor microenvironment. It has been recognized as a promising clinical antitumor agent by virtue of its widely accepted therapeutic efficacy. This paper reviewed the anti-breast cancer action and its molecular mechanisms of TP on the basis of the relevant literature in the past ten years,and proposed application strategies in view of the inadequacy of TP to provide a reference for further research on the application of TP in the treatment of breast cancer.
Breast Neoplasms/genetics* ; Diterpenes/pharmacology* ; Epoxy Compounds ; Female ; Humans ; Phenanthrenes ; Tumor Microenvironment

This study was purposed to investigate the effect of triptolide on bortezomib-induced apoptosis in multiple myeloma cell line NCI-H929(H929). MTT assay was applied to detect the inhibitory effects of triptolide and bortezomib alone or combined at different concentrations on H929 cells, the cell apoptosis was assayed by flow cytometry with Annexin V-FITC/PI staining. The results showed that both triptolide (10 - 100 ng/ml) and bortezomib (10 - 100 nmol/L) alone or combination inhibited the proliferation of MM cell line H929 in a concentration-dependent manner. The apoptotic rate of H929 cells in group of triptolide combined with bortezomib was much higher than that in groups of single drug or control; moreover, the apoptotic rate of H929 cells treated by non-inhibitory concentration of triptolide (10 ng/ml) combined with bortezomib (40 nmol/L) for 24 h was significantly higher than that by bortezomib alone (P < 0.05). It is concluded that triptolide can significantly enhance the pro-apoptotic activity of bortezomib in MM cells.
Apoptosis ; drug effects ; Boronic Acids ; pharmacology ; Bortezomib ; Cell Line, Tumor ; Diterpenes ; pharmacology ; Epoxy Compounds ; pharmacology ; Humans ; Multiple Myeloma ; pathology ; Phenanthrenes ; pharmacology ; Pyrazines ; pharmacology

Along with the deep-going researches on mechanism of apoptosis, the apoptosis inducers as anticancer drugs have been the hot points of researches for new drugs. In this paper are reviewed a number of related articles on the progress in cell apoptosis inducers including the derivative anthraquinone, saponin, flavonids and terpines. The mechanisms are analyzed and discussed. The researches into the molecular mechanisms of inducer can provide the theoretical basis for discovering new compound, and can find out the apoptosis inducers with high efficiency and low toxicity. There is hope of developing apoptosis inducers into safe and effectual anticancer drugs.
Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Diterpenes, Abietane ; Emodin ; pharmacology ; Flavones ; pharmacology ; Humans ; Neoplasms ; drug therapy ; metabolism ; pathology ; Phenanthrenes ; pharmacology ; Saponins ; pharmacology

OBJECTIVETo develop a drug delivery system triptolide-polyethylenimine-cyclodextrin and to evaluate its anticancer activity in vitro.

METHODSTriptolide was conjugated to polyethylenimine-cyclodextrin by N, N'-carbonyldiimidazole to form triptolide-polyethylenimine-cyclodextrin. (1)H-NMR, FT-IR and XRD were used to confirm its structure. The anticancer effect of the polymer was assessed by MTT assay, erasion trace test and hematoxylin-eosin staining. The potential to condense siRNA and to delivery siRNA into cytoplasm was demonstrated by gel retardation assay, zeta-potential determination and fluorescence staining.

RESULTSTriptolide was successfully conjugated to polyethylenimine-cyclodextrin and the conjugation rate of triptolide was 10% (w/w). siRNA was effectively condensed by the polymer at the N/P ratio of 5, and its particle size was 300 ±15 nm and zeta potential was 8 ±2.5 mV. MTT assay, erasion trace test and hematoxylin-eosin staining revealed that triptolide-polyethylenimine-cyclodextrin had anticancer effect and low cytotoxicity to normal cells. The polymer was able to deliver siRNA to the cytoplasm effectively as demonstrated by fluorescence staining.

CONCLUSIONTriptolide-polyethylenimine-cyclodextrin is able to inhibit the growth and migration of cancer cells in vitro and to carry siRNA into cells effectively. It is potential to be used as a novel prodrug for co-delivery of gene and drug in cancer treatment.

Antineoplastic Agents ; administration & dosage ; pharmacology ; Cell Line, Tumor ; Cyclodextrins ; Diterpenes ; administration & dosage ; pharmacology ; Drug Carriers ; Epoxy Compounds ; administration & dosage ; pharmacology ; Humans ; Nanoparticles ; Phenanthrenes ; administration & dosage ; pharmacology ; Polyethyleneimine ; Polymers

The aim of this study was to investigate the anti-proliferation and pro-apoptosis of triptolide on Jurkat cell line in acute T lymphocytic leukemia. The Jurkat cells were treated with various concentrations of triptolide (0, 1, 2, 4, 8, 16 microg/L) for 12 hours. The inhibitory ratio was measured by Cell Counting Kit-8 assay. The effects of triptolide on apoptosis of Jurkat cells were determined by DNA fragmentation (DNA ladder), Hoechst 33258, PI and Annexin V-FITC/PI double staining. The results demonstrated that triptolide inhibited the proliferation of Jurket cells. The 50% inhibitory concentration (IC(50)) was 4.0 microg/L. Chromatin condensation in the cells treated with triptolide could be seen by light microscopy. DNA electrophoresis showed evidence of nuclear fragmentation (DNA ladder). The hypoploid (sub-G(1)) population was increased after treatment with triptolide. The translocation of phosphatidylserine at the outer surface of the cell plasma membrane could be induced by triptolide. After treatment with triptolide for 12 hours, the rates of apoptotic cells were significantly increased. Moreover, these pro-apoptosis effects were in time-dependent manner. It is concluded that triptolide can inhibit the proliferation and induce the apoptosis of Jurkat cells. This study provides experimental basis for clinical use of triptolide in leukemia therapy.
Antineoplastic Agents, Alkylating ; pharmacology ; Apoptosis ; drug effects ; Cell Proliferation ; drug effects ; Diterpenes ; pharmacology ; Epoxy Compounds ; pharmacology ; Humans ; Jurkat Cells ; Phenanthrenes ; pharmacology

Tumors are major chronic diseases and seriously threaten human health all over the world. How to effectively control and cure tumors is one of the most pivotal problems in the medical field. At present,surgery,radiotherapy and chemotherapy are still the main treatment methods. However,the side effects of radiotherapy and chemotherapy cannot be underestimated. Therefore,it is of great practical significance to find new anti-cancer drugs with low toxicity,high efficiency and targeting to cancer cells. With the increasing incidence of tumor,the anti-tumor effect of traditional Chinese medicine has increasingly become a research hotspot. Triptolide,which is a natural diterpenoid active ingredient derived from of Tripterygium wilfordii,as one of the highly active components,has anti-inflammatory,immunosuppressive,anti-tumor and other multiple effects. A large number of studies have confirmed that it has good anti-tumor activity against various tumors in vivo and in vitro. It can play an anti-tumor role by inhibiting the proliferation of cancer cells,inducing apoptosis of cancer cells,inducing autophagy of cancer cells,blocking the cell cycle,inhibiting the migration,invasion and metastasis of cancer cells,reversing multidrug resistance,mediating tumor immunity and inhibiting angiogenesis. On the basis of literatures,this paper reviews the anti-tumor effect and mechanism of triptolide,and analyzes the current situation of triptolide combined with other chemotherapy drugs,in order to promote deep research and better clinical application about triptolide.
Antineoplastic Agents, Phytogenic ; pharmacology ; Apoptosis ; Autophagy ; Cell Cycle Checkpoints ; Diterpenes ; pharmacology ; Epoxy Compounds ; pharmacology ; Humans ; Neoplasms ; drug therapy ; Phenanthrenes ; pharmacology ; Tripterygium ; chemistry

As a major active component extracted from traditional Chinese herb Tripterygium wilfordii Hook F, triptolide exhibits multiple pharmacological effects. Autophagy is an evolutionary conserved intracellular catabolic process involved in cytoplasmic materials degradation. Autophagic dysfunction contributes to the pathologies of many human diseases, which makes it a promising therapeutic target. Recent studies have shown that triptolide exerts neuroprotection, anti-tumor activities, organ toxicity, and podocyte protection by modulating autophagy. This article highlights the current information on triptolide-modulated autophagy, analyzes the possible pathways involved, and describes the crosstalk between autophagy and apoptosis modulated by triptolide, in hope of providing implications for the roles of autophagy in pharmacological effects of triptolide and expanding its novel usage as an autophagy modulator.
Animals ; Apoptosis ; drug effects ; Autophagy ; drug effects ; Diterpenes ; pharmacology ; Epoxy Compounds ; pharmacology ; Humans ; Neoplasms ; drug therapy ; pathology ; Neuroprotective Agents ; pharmacology ; Phenanthrenes ; pharmacology ; Podocytes ; drug effects

OBJECTIVETo investigate the impact of protein kinase B (Akt2) allele deletion on testicular reproductive function, and to discuss the regulatory effect of Cryptotanshinone on the reproductivity of male mice with Akt2 allele deletion and its molecular mechanism.

METHODSFifteen Akt2 +/+ male mice were randomly divided into Groups A (baseline control, n = 7) and B (stimulation, n = 8), and another 29 Akt2 -/- male mice into C (baseline control, n = 7), D (stimulation, n = 8), E (solvent, n = 7) and F (Cryptotanshinone, n = 7). Groups B and D underwent human chorionic gonadotropin (HCG) stimulation tests at 5 IU / 20 g, while A and C received physiological saline, all for 4 hours; Group F were given gastric lavage of Cryptotanshinone, while E solvent only, at 600 mg/kg twice a day for 8 weeks, both subjected to oral glucose tolerance tests (OGTT) at 2 g/kg before and after the treatment. The body and bilateral testis weights were obtained, the serum testosterone (T) level measured, and the expressions of testicular steroid hormone synthesis and glycometabolism-related genes determined by RT-PCR.

RESULTSOGTT showed that the level of blood glucose was significantly higher in Groups C and D than in A and B ([10.38 +/- 1.42] and [10.96 +/- 1.81] mmol/L vs [7.92 +/- 0.63] and [8.32 +/- 0.44] mmol/L, P < 0.05), but had no significant differences at different time points in E and F (P > 0.05). The testis weight was remarkably higher in Groups C and D than in A and B ([0.17 +/- 0.01] and [0.17 +/- 0.01] g vs [0.15 +/- 0.01] and [0.15 +/- 0.02] g, P < 0.05), but exhibited no obvious difference in E and F, nor were there any significant differences in body weight among different groups (P > 0.05). The serum T level was markedly higher in Group C than in A ([9.08 +/- 1.59] nmol/L vs [6.42 +/- 0.95] nmol/L, P < 0.05), but evidently lower in F than in E ([5.94 +/- 0.49] nmol/L vs [8.18 +/- 1.44] nmol/L, P < 0.05). The baseline expression levels of Cyp11, Cyp17, 3B-HSD, Star, Gsk3beta, Erk-1, and MCM2 mRNA were significantly higher in Group C than in A (P < 0.05). After HCG stimulation, the expressions of Cyp11, Cyp17, 3B-HSD, and Star mRNA were remarkably increased in B and D, but with no obvious difference between the two groups (P > 0.05), while the expressions of Cyp11, Cyp17, 3B-HSD, Star, Gsk3beta, Erk-1, and MCM2 mRNA markedly decreased in F as compared with E (P < 0.05).

CONCLUSIONAkt2 gene deletion may affect glycometabolism and testicular function, and cause abnormal glycometabolism and androgen secretion in male mice, whose molecular mechanism is associated with the elevated expressions of the key glycometabolic molecules and of the key enzymes for androgen synthesis. Cryptotanshinone can reduce the levels of androgens by down-regulating the expressions of the key enzymes for androgen synthesis.

Androgens ; blood ; Animals ; Insulin Resistance ; Male ; Mice ; Mice, Inbred C57BL ; Phenanthrenes ; pharmacology ; Proto-Oncogene Proteins c-akt ; genetics ; Sequence Deletion