ABSTRACT
By utilizing a supramolecular complex rather than an individual molecule as a deformable and elastic substitutional component, we put forward a solid-solution strategy and demonstrate an example of how two related yet non-isostructural crystalline host-guest compounds can form molecular solid solutions. Interestingly, such a strategy can effectively and continuously modulate the molecular motion and phase transition in them, as revealed by the variable-temperature/frequency dielectric responses.
ABSTRACT
Excessive nitric oxide (NO) causes extensive damage to the nervous system, and the adrenergic system is disordered in many neuropsychiatric diseases. However, the role of the adrenergic system in protection of the nervous system against sodium nitroprusside (SNP) injury remains unclear. In this study, we investigated the effect of ganoderic acid A (GA A) against SNP injury in neural cells and the role of adrenergic receptors in GA A neuroprotection. We found that SNP (0.125-2 mM) dose-dependently decreased the viability of both SH-SY5Y and PC12 cells and markedly increased NO contents. Pretreatment with GA A (10 µM) significantly attenuated SNP-induced cytotoxicity and NO increase in SH-SY5Y cells, but not in PC12 cells. Furthermore, pretreatment with GA A caused significantly higher adrenaline content in SH-SY5Y cells than in PC12 cells. In order to elucidate the mechanism of GA A-protecting SH-SY5Y cells, we added adrenaline, phentolamine, metoprolol, or ICI 118551 1 h before GA A was added to the culture medium. We found that addition of adrenaline (10 µM) significantly improved GA A protection in PC12 cells. The addition of ß1-adrenergic receptor antagonist metoprolol (10 µM) or ß2-adrenergic receptor antagonist ICI 118551 (0.1 µM) blocked the protective effect of GA A, whereas the addition of α-adrenergic receptor antagonist phentolamine (0.1 µM) did not affect GA A protection in SH-SY5Y cells. These results suggest that ß-adrenergic receptors play an important role in the protection of GA A in SH-SY5Y cells against SNP injuries, and excessive adrenaline system activation caused great damage to the nervous system.
Subject(s)
Heptanoic Acids/pharmacology , Lanosterol/analogs & derivatives , Neurons/drug effects , Neuroprotective Agents/pharmacology , Nitric Oxide/antagonists & inhibitors , Receptors, Adrenergic, beta/metabolism , Animals , Cell Survival/drug effects , Dose-Response Relationship, Drug , Heptanoic Acids/chemistry , Humans , Lanosterol/chemistry , Lanosterol/pharmacology , Molecular Conformation , Neuroprotective Agents/chemistry , Nitric Oxide/metabolism , Nitroprusside/pharmacology , Oxidative Stress/drug effects , PC12 Cells , Rats , Structure-Activity Relationship , Tumor Cells, CulturedABSTRACT
The aim of this study is to investigate the synergism of low dose of actinomycin D (LDActD) to the cytotoxicity of cisplatin (CDDP) on KB cells. The role of P53 reactivation by LDActD in the synergism and its mechanism were further studied. Cell viability was determined by MTT assay. Apoptosis was determined by AnnexinV-FITC/PI staining. Mitochondrial membrane potential (MMP) was detected by JC-1 staining. Expression of proteins was detected by Western blotting (WB) and/or immunofluorescence (IF). Molecular docking of actinomycin D (ACTD) to Mouse double minute 2 homolog (MDM2) and Mouse double minute 2 homolog X (MDMX). MDMX was analyzed by Discovery Studio. The content of P53-MDM2 complex was detected by ELISA assay. The cytotoxicity of CDDP was increased by the combination of LDActD in kinds of cancer cells. Molecular docking showed strong interaction between ACTD and MDM2/MDMX. Meanwhile, LDActD significantly decreased P53-MDM2 complex. Significant increase of the apoptotic activity by the combination therapy in KB cells is P53 upregulated modulator of apoptosis (PUMA) dependent. In addition to the decrease in MMP, LDActD increased P53 regulated protein and decreased BCL-XL in KB cells. LDActD efficiently enhanced the cytotoxicity of CDDP in cancer cells and induced P53-PUMA-dependent and mitochondria-mediated apoptosis in KB cells. The reactivation of P53 was probably achieved by disturbing the interaction of P53 and MDM2/MDMX.
Subject(s)
Cisplatin/pharmacology , Dactinomycin/pharmacology , Tumor Suppressor Protein p53/drug effects , Animals , Apoptosis/drug effects , Benzimidazoles/chemistry , Carbocyanines/chemistry , Cell Survival/drug effects , Dactinomycin/chemistry , Humans , Imidazoles/pharmacology , KB Cells , Membrane Potential, Mitochondrial/drug effects , Mice , Molecular Docking Simulation , Molecular Structure , Signal Transduction/drug effects , Tumor Suppressor Protein p53/metabolismABSTRACT
OBJECTIVE To evaluate the effect of Guizhi Fuling Capsule active pharmaceutical ingredient (API) and its fractions on human breast cancer cells proliferation by high-throughput screening assay. METHODS The crude fractions were obtained from the extraction and elution of the API of Guizhi Fuling Capsule, and 929 standard fractions were obtained by the optimal separation conditions. Sulforhodamine B (SRB) method was used to evaluate the effects of the Guizhi Fuling capsule API and 929 kinds of fractions on the proliferation of human breast cancer cells MCF- 7 and MDA- MB- 231. RESULTS The Guizhi Fuling capsule API had a strong ability to inhibit the proliferation of MCF-7 cells at high concentration and the ability to inhibit MDA-MB-231 cells' proliferate at low concentration follow?ing 72 h treatment;some samples of 929 fractions (5 μg·mL-1) was found to have a breast cancer cell growth inhibition rate above 50%, without toxicity on HUVECs proliferation. CONCLUSION The API of Guizhi Fuling capsule had significant cytotoxicity effects on these two human breast cancer cells, with significant concentration- and time-dependent manner.
