RESUMEN

Glioblastoma (GBM) is a lethal cancer characterized by hypervascularity and necrosis associated with hypoxia. Here, it is found that hypoxia preferentially induces the actin-binding protein, Transgelin (TAGLN), in GBM stem cells (GSCs). Mechanistically, TAGLN regulates HIF1α transcription and stabilizes HDAC2 to deacetylate p53 and maintain GSC self-renewal. To translate these findings into preclinical therapeutic paradigm, it is found that sodium valproate (VPA) is a specific inhibitor of TAGLN/HDAC2 function, with augmented efficacy when combined with natural borneol (NB) in vivo. Thus, TAGLN promotes cancer stem cell survival in hypoxia and informs a novel therapeutic paradigm.

Asunto(s)

Neoplasias Encefálicas , Glioblastoma , Proteínas Musculares , Humanos , Glioblastoma/tratamiento farmacológico , Glioblastoma/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Acetilación , Neoplasias Encefálicas/metabolismo , Proteínas de Microfilamentos/metabolismo , Hipoxia/metabolismo , Células Madre Neoplásicas/metabolismo

RESUMEN

Piperlongumine (PL) can selectively inhibit the proliferation of various cancer cells by increasing reactive oxygen species (ROS) level to cause a redox imbalance in cancer cells rather than in normal cells. However, the clinical application of PL is limited by its poor cellular uptake. Natural borneol (NB) is extracted from the fresh branches and leaves of Cinnamomum camphora (L.) Presl. with the purity of (+)-borneol no less than 96.0%. NB has been often used as an adjuvant agent to promote the cellular uptake of other drugs. This study aims to investigate the effect of NB on the cellular uptake of PL for improving its antiglioma efficacy and underlying mechanism. NB obviously promoted the cellular uptake of PL with a 1.3-fold increase in the maximum peak concentration and an earlier peak time of 30 min in C6 glioma cells. The cellular uptake of PL was enhanced by NB through down-regulating the expression levels of P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2). The combination of NB and PL significantly induced higher levels of ROS, which increased apoptosis and enhanced G2/M cycle arrest of C6 glioma cells, compared to PL alone administration. NB-enhanced antiglioma efficacy of PL without side effects was confirmed in tumor-bearing mice, which was attributed to the improved cellular uptake of PL. The distribution of PL in the tumor tissue of combined group increased 2.39 times than that of PL-treated group. We firstly report NB as an adjuvant agent to improve the antiglioma efficacy of PL in a ROS-dependent manner, which is due to the enhanced cellular uptake of PL by NB though down-regulating the expression levels of ABCB1 and ABCG2. This work provides a new strategy to promote the cellular uptake of PL with great potential for the treatment of glioma.

Asunto(s)

Dioxolanos , Glioma , Animales , Ratones , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2 , Especies Reactivas de Oxígeno/metabolismo , Apoptosis , Línea Celular Tumoral , Proteínas de Neoplasias/metabolismo , Dioxolanos/farmacología , Dioxolanos/uso terapéutico , Adyuvantes Inmunológicos/farmacología , Glioma/tratamiento farmacológico

RESUMEN

Objectives Due to its high morbidity, high mortality, and high disability, stroke has been the first cause of death and the major cause of adult disability in China. Natural borneol has been widely utilized in Traditional Chinese Medicine to promote drug absorption. Formononetin is a natural isoflavonoid with potent neuroprotective activity but poor brain delivery. Methods This study aimed to screen the optimum proportion that natural borneol promotes formononetin entry into the brain, evaluate the anti-cerebral ischaemia efficacy of formononetin/natural borneol combination in middle cerebral artery occlusion/reperfusion model rats, and clarify the possible mechanism for natural borneol's promoting formononetin delivery in the brain. Key findings Our studies exhibited that natural borneol remarkably promoted formononetin entry into the brain when combined with formononetin in a 1 : 1 molar ratio and notably improved neuro-behavioural scores and reduced the infarct of middle cerebral artery occlusion/reperfusion model rats. This study further discovered that the enhanced anti-cerebral ischaemia effect resulted from natural borneol increasing the permeability of the blood-brain barrier to elevate formononetin concentration in the brain rather than the pharmacodynamic synergy or addition between formononetin and natural borneol. Conclusions The study provides a good strategy to screen drug combinations for the treatment of brain disease by combining natural borneol with other drugs.

Asunto(s)

Isquemia Encefálica , Daño por Reperfusión , Animales , Ratas , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Canfanos/farmacología , Isquemia Encefálica/tratamiento farmacológico , Encéfalo , Daño por Reperfusión/tratamiento farmacológico

RESUMEN

OBJECTIVES: Natural borneol and synthetic borneol were commonly used to treat ischaemic stroke in clinical practice. This study evaluated their different neuroprotective effects on the remodelling and repair of the neurovascular unit (NVU) after cerebral ischaemia. METHODS: We evaluated the different effects of borneol through neurological test and staining methods in cerebral ischaemia injury. Western blot, immunohistochemistry and transmission electron microscopy were used to evaluate the reparative effects of borneol on NVU. KEY FINDINGS: The prevention and treatment of borneol could prolong recovery time, reduce body temperature and cerebral infarction rate and improve pathological conditions. Further investigations revealed that borneol could inhibit the expression of DII4, Hes1, Hes5 and p65 and increase the Nissl body number and microvessel density. They also inhibited the activation of the microglia. It was also observed through an ultramicroelectron microscope that the structural stability of the NVU has also been repaired. Moreover, natural borneol shows better results in most indicators when compared with synthetic borneol. CONCLUSIONS: Natural borneol showed a stronger effectiveness and had better regulation and neuroprotection on the NVU when compared with synthetic borneol, indicating that it may be better to use natural borneol in the prescription of Chinese patent medicine in clinical practice.

Asunto(s)

Isquemia Encefálica/tratamiento farmacológico , Canfanos/farmacología , Fármacos Neuroprotectores/farmacología , Animales , Temperatura Corporal/efectos de los fármacos , Isquemia Encefálica/patología , Canfanos/química , Modelos Animales de Enfermedad , Masculino , Microglía/efectos de los fármacos , Microscopía Electrónica de Transmisión , Fármacos Neuroprotectores/química , Ratas , Ratas Sprague-Dawley

RESUMEN

Natural borneol is an important traditional Chinese medicine herb with resuscitation-inducing, antipyretic and analgesic effects, and has been widely used in the fields of medicine, perfume and chemical industry. At present, natural borneol is short supply, with promising market development prospects. This paper summarized the distribution of borneol plant resources, cultivation status and molecular biological research progress, in the expectation of providing basis and ideas for the research and application of natural borneol.

Asunto(s)

Canfanos , Medicamentos Herbarios Chinos , Medicina Tradicional China

RESUMEN

Natural borneol is an important traditional Chinese medicine herb with resuscitation-inducing, antipyretic and analgesic effects, and has been widely used in the fields of medicine, perfume and chemical industry. At present, natural borneol is short supply, with promising market development prospects. This paper summarized the distribution of borneol plant resources, cultivation status and molecular biological research progress, in the expectation of providing basis and ideas for the research and application of natural borneol.

Asunto(s)

Canfanos , Medicamentos Herbarios Chinos , Medicina Tradicional China

RESUMEN

Background: Lung cancer has a high mortality rate and is resistant to multiple chemotherapeutics. Natural Borneol (NB) is a monoterpenoid compound that facilitates the bioavailability of drugs. In this study, we investigated the effects of NB on chemosensitivity in the A549 human lung adenocarcinoma cell line and to elucidate therapeutic molecular target of NB. Methods: The chemosensitivity effects of NB in A549 cells were examined by MTT assay. The mechanism of NB action was evaluated using flow cytometry and Western blotting assays. Surface plasmon resonance (SPR) and LC-MS combined analysis (MS-SPRi) was performed to elucidate the candidate molecular target of NB. The chemosensitizing capacity of NB in vivo was assessed in nude mice bearing A549 tumors. Results: NB pretreatment sensitized A549 cells to low doxorubicin (DOX) dosage, leading to a 15.7% to 41.5% increase in apoptosis. This increase was correlated with ERK and AKT inactivation and activation of phospho-p38 MAPK, phospho-JNK, and phosphor-p53. Furthermore, this synergism depends on reactive oxygen species (ROS) generation. MS-SPRi analysis revealed that transient receptor potential melastatin-8 (TRPM8) is the candidate target of NB in potentiating DOX killing potency. Genetically, TRPM8 knock-down significantly suppresses the chemosensitizing effects of NB and inhibits ROS generation through restraining calcium mobilization. Moreover, pretreatment with NB synergistically enhances the anticancer effects of DOX to delay tumor progression in vivo. Conclusions: These results suggest that TRPM8 may be a valid therapeutic target in the potential application of NB, and show that NB is a chemosensitizer for lung cancer treatment.

Asunto(s)

Calcio/metabolismo , Canfanos/farmacología , Doxorrubicina/farmacocinética , Canales Catiónicos TRPM/metabolismo , Células A549 , Animales , Línea Celular Tumoral , Sinergismo Farmacológico , Humanos , Ratones , Ratones Desnudos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacos , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo

RESUMEN

Despite the effective targeting of the epidermal growth factor receptor (EGFR), the use of gefitinib (GFT) for nonsmall cell lung cancer (NSCLC) treatment meets a failure because of the insufficient drug accumulation in the tumor region. Therefore, developing chemosensitizers of GFT with synergistic therapeutic effects is urgently needed for advanced cancer therapy. Herein, a natural chemosensitizer, natural borneol (NB), is reformulated as an oil-in-water nanoemulsion to enhance its solubility, distribution, and to ultimately increase the therapeutic index with GFT. The nanolization of NB (NBNPs) displays stronger targeted delivery and cytotoxicity than NB by selectively identifying eight specific protein targets in A549 NSCLC cells as revealed by the proteomic studies. Consistently, NBNPs realize stronger chemosensitization effects than NB with GFT by effectively regulating EGFR/EHD1-mediated apoptosis in A549 NSCLC cells. Owing to the satisfying synergistic effect between NBNPs and GFT, the combined therapy not only enhances the anticancer ability of GFT against NSCLC proliferation but also avoids heavy double toxicity in vivo. This finding demonstrates the effective synergism between NBNPs and GFT with clear mechanistic investigation and is expected to extend the application of NBNPs as a novel chemosensitizer for advanced cancer chemotherapy.

Asunto(s)

Antineoplásicos/farmacología , Canfanos/farmacología , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Gefitinib/farmacología , Neoplasias Pulmonares/tratamiento farmacológico , Nanopartículas/química , Proteínas de Transporte Vesicular/antagonistas & inhibidores , Animales , Antineoplásicos/química , Apoptosis/efectos de los fármacos , Canfanos/química , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Ensayos de Selección de Medicamentos Antitumorales , Emulsiones/química , Femenino , Gefitinib/química , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Estructura Molecular , Neoplasias Experimentales/tratamiento farmacológico , Neoplasias Experimentales/metabolismo , Neoplasias Experimentales/patología , Tamaño de la Partícula , Propiedades de Superficie , Proteínas de Transporte Vesicular/metabolismo

RESUMEN

Doxorubicin (DOX) as a first-line chemotherapeutic drug has been widely used for therapy of human cancers. However, side effects and chemo-resistance severely blocked its clinic application. Herein, natural borneol (NB) as a novel monoterpenoid chemosensitizer was found to have the potential to increase the blood brain barrier (BBB) permeability and intracellular uptake of DOX in vitro, and synergistically enhanced DOX-induced cytotoxicity in human glioma cells. NB treatment significantly potentiated DOX-induced G2/M cell cycle arrest by triggering reactive oxygen species (ROS)-mediated DNA damage. NB also enhanced DOX-induced dysfunction of MAPKs and PI3 K/AKT pathways. Furthermore, U251 human glioma xenograft growth in vivo was also effectively inhibited by combined treatment of DOX with NB through induction of G2/M-phase arrest and antiangiogenesis. Taken together, our finding validated that NB could act as novel chemosensitizer to enhance DOX-induced anticancer efficacy, and strategy of using NB and DOX could be a high efficient way in therapy of human cancers.

Asunto(s)

Antineoplásicos/uso terapéutico , Canfanos/uso terapéutico , Doxorrubicina/uso terapéutico , Glioma/tratamiento farmacológico , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal , Animales , Antineoplásicos/farmacología , Canfanos/química , Canfanos/farmacología , Línea Celular Tumoral , Daño del ADN , Doxorrubicina/farmacología , Puntos de Control de la Fase G2 del Ciclo Celular/efectos de los fármacos , Glioma/patología , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , Masculino , Ratones Desnudos , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Modelos Biológicos , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo

RESUMEN

OBJECTIVE: To investigate the effect of natural and synthetic borneol on the transdermal absorption of emodin. METHODS: The supplying and receiving solutions containing emodin were selected from the abdominal skin of mice in vitro, and the samples were analyzed by HPLC. The cumulative permeability, permeability rate and permeability enhancement factor were used as the evaluation indexes of the permeability enhancement effect. RESULTS: The saline containing 1% Tween 80-80% ethanol and 60% ethanol could increase the solubility of emodin to 648 μg•mL -1 and obtain conditions of leaking trough. The penetration rate of emodin was 648 μg•mL - 1 > 569 μg•mL -1 > 457 μg•mL -1 in the range of concentration. The penetration enhancement effect of synthetic borneol was 2% > 4% > 1% > blank control group > 3% and 5%, and the steady-state permeation rates of 2% natural borneol (15.90 μg•cm- 2•h - 1 ) were higher than those of 2% synthetic borneol(12.44 μg•cm-2•h-1). CONCLUSION: Natural borneol and synthetic borneol can promote the transdermal penetration of emodin, which is limited by their concentration. This provides an experimental basis for the selection of emodin transdermal enhancers.

RESUMEN

Paclitaxel (PTX) has been used in a variety of malignancies for inhibiting tumor development and improving survival. However, its clinical application is limited due to poor solubility, drug resistance, and gastrointestinal reactions. Natural borneol (NB), as a promoter, could help to improve drug absorption. Therefore, the aims of the present study were to investigate the ability of NB to synergize with PTX to induce human esophageal squamous cell carcinoma (ESCC) cells apoptosis and the underlying mechanism of synergistic effects. In this study, our findings showed that NB could effectively synergize with PTX to inhibit the survival of ESCC cells by inducing apoptosis. The molecular mechanism by western blotting elucidated that combination treatment with PTX and NB significantly activated apoptotic pathway by triggering upregulation of cleaved caspase-3 expression and downregulation of survivin and P-AKT expression. These results demonstrated that NB could strongly potentiate PTX-induced apoptosis in ESCC cells through suppressing PI3K/AKT pathway. Thus, the combination therapy with NB and PTX might be a promising treatment strategy for human esophageal cancer. PRACTICAL APPLICATION: Esophageal cancer is one of the most common cancers in the world. It has brought about a major public health problem. Many natural agents have been employed in the synergized treatments of esophageal cancer. This study provides a comprehensive way to investigate the ability of borneol to synergize with paclitaxel to induce human esophageal squamous cell carcinoma cells apoptosis and the underlying mechanism of synergistic effects. The research showed that the combination treatment with some natural agents might be a promising treatment strategy for human esophageal cancer.

Asunto(s)

Apoptosis/efectos de los fármacos , Canfanos/farmacología , Paclitaxel/farmacología , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Carcinoma de Células Escamosas/tratamiento farmacológico , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Sinergismo Farmacológico , Neoplasias Esofágicas/tratamiento farmacológico , Carcinoma de Células Escamosas de Esófago , Humanos , Inhibidores de las Quinasa Fosfoinosítidos-3 , Proteínas Proto-Oncogénicas c-akt/antagonistas & inhibidores

RESUMEN

Borneol is a monoterpene that is widely used in traditional Chinese medicine. There are two different products sold in Taipei's traditional Chinese medicine market, natural and chemically synthesized borneol. Chemically synthesized borneol contains four stereoisomers, (+)-isoborneol, (-)-isoborneol, (-)-borneol, and (+)-borneol. The ratio of these four isomers in chemically synthesized and natural borneol products was determined by gas chromatography mass spectrometry. A huge variation between these products is highlighted in this survey. The results suggest that the Food and Drug Administrations in Asian countries should establish a regulatory standard regarding the ratio of the four different borneol isomers in both natural and chemically synthesized borneol.

Asunto(s)

Canfanos/análisis , Canfanos/química , Cromatografía de Gases y Espectrometría de Masas , Medicina Tradicional China , Estructura Molecular , Taiwán

RESUMEN

Natural borneol (NB, called "Bingpian") is an important traditional Chinese medicine to restore consciousness, remove heat and relieve pain, all of which are inflammation-related diseases. Recently, due to the limited source of NB, synthetic borneol (SB) is widely used as a substitute for NB in clinics. However, little is known about the effects of SB instead of NB. Herein, the aim of the present study was to compare NB and SB on chemical profiles by gas chromatography-mass spectrometer (GC-MS) analysis, anti-inflammatory activity in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages, and ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) metabolomic approaches in endotoxic fever induced in rats. Results showed that, in total, 13 volatile components could be identified in NB and SB by GC-MS analysis, in which a significant difference between them still existed. The main constituents in SB were iso-borneol and borneol, while borneol contributes to 98.96% of the amount in NB. Additionally, both NB and SB exhibited remarkable anti-inflammatory effects to reduce the level of inflammatory factors including NO, TNF-α and IL-6 in LPS-induced RAW 264.7 macrophages, and lower the high body temperature in rats with endotoxic fever induced by LPS. Moreover, it seems that NB exhibited higher efficacy than SB. The unequal bioactive efficiency between NB and SB was also indicated by means of non-targeting metabolomics. Based on UPLC-Q-TOF/MS technology, 12 biomarkers in the serum of fever rats were identified. Pathway analysis revealed that the anti-fever effect of NB and SB was related to regulating the abnormal glycerophospholipid, linoleic acid and alpha-linoleic acid metabolism pathways in the fever model. Results indicated that there was still a great difference between NB and SB involving chemical constituents, anti-inflammation activity and the ability to regulate the abnormal metabolism pathways of the fever model. Certainly, further studies are warranted to better understand the replacement rationale in medicinal application.

Asunto(s)

Antiinflamatorios/química , Canfanos/química , Medicamentos Herbarios Chinos/química , Fiebre/tratamiento farmacológico , Animales , Antiinflamatorios/aislamiento & purificación , Antiinflamatorios/farmacología , Canfanos/aislamiento & purificación , Canfanos/farmacología , Cromatografía Líquida de Alta Presión , Evaluación Preclínica de Medicamentos , Medicamentos Herbarios Chinos/aislamiento & purificación , Medicamentos Herbarios Chinos/farmacología , Fiebre/inmunología , Lipopolisacáridos/farmacología , Masculino , Metabolómica , Ratones , Células RAW 264.7 , Ratas Sprague-Dawley , Espectrometría de Masas en Tándem

RESUMEN

CONTEXT: Selectively opening the blood-tumour barrier (BTB) is critical to deliver antitumour drugs from blood to tumour tissues. The BTB problem is attributed to the tight junctions (TJs), which consist of several transmembrane proteins. OBJECTIVE: To investigate whether borneol could open the BTB by affecting TJ-associated proteins ZO-1, occludin, claudin-5 and F-actin in the rat model of C6 glioma. MATERIALS AND METHODS: The plasma and brain tissue of C6 glioma rats were collected at different points after rats were administered with 35 or 140 mg/kg borneol and 0.5% CMC-Na, respectively. The permeability of BTB was assessed by cisplatin extravasation. The mRNA and protein expression levels of TJ-associated proteins were determined by QPCR, ELISA and immunohistochemistry. RESULTS: The cisplatin bioavailability in the brain tissue of C6 glioma rats administered either 35 or 140 mg/kg borneol and 0.5% CMC-Na were 415.07, 227.04 and 192.07 (mg/mL/h), respectively. The mRNA and protein expression levels of ZO-1 and F-actin began to decrease from the time point of 2 min; the lowest levels in the borneol high-dose (46.7% decrease for ZO-1 and 63.3% for F-actin compared with control) and low-dose groups (54.3% for ZO-1; 77.9% for F-actin) appeared at the time points of 30 and 45 min, respectively. Thereafter, the levels were gradually restored to the level of borneol at 0 h. Occludin and claudin-5 expression levels were not significantly modified. CONCLUSION: Borneol could selectively open the BTB and consequently increase BTB permeability, and this mechanism is associated with the down-regulation of ZO-1 and F-actin.

Asunto(s)

Barrera Hematoencefálica/metabolismo , Neoplasias Encefálicas/metabolismo , Encéfalo/metabolismo , Canfanos/farmacología , Glioma/metabolismo , Proteínas de Uniones Estrechas/biosíntesis , Animales , Barrera Hematoencefálica/efectos de los fármacos , Encéfalo/efectos de los fármacos , Neoplasias Encefálicas/tratamiento farmacológico , Canfanos/uso terapéutico , Permeabilidad Capilar/efectos de los fármacos , Permeabilidad Capilar/fisiología , Línea Celular Tumoral , Relación Dosis-Respuesta a Droga , Regulación Neoplásica de la Expresión Génica , Glioma/tratamiento farmacológico , Masculino , Ratas , Ratas Sprague-Dawley , Uniones Estrechas/efectos de los fármacos , Uniones Estrechas/metabolismo

RESUMEN

Curcumin (Cur), an active ingredient from the rhizome of the plant Curcuma longa, has wide anticancer activities. However, due to its poor solubility and hence poor absorption, Cur has limited clinical applications. It is therefore important to develop an effective method to improve its absorption. Natural borneol (NB), a terpene and bicyclic organic compound, has been extensively used as a food additive, and our previous studies show that it can improve the uptake of Cur in cancer cells. However, the anticancer mechanism of NB/Cur remains unclear. In this study, the effects of NB/Cur on HepG2 cells were investigated by proteomic analysis. The results showed that 32 differentially expressed proteins identified by matrix assisted laser desorption ionization time-of-flight mass spectrometry were significantly changed after NB/Cur treated HepG2 cells for 24 h. Moreover, 17 proteins increased and 12 proteins decreased significantly. Biological progress categorization demonstrated that the identified proteins were mainly associated with cell cycle and apoptosis (28.1%). Subcellular location categorization exhibited that the identified proteins were mainly located in nucleus (28.1%) and mitochondrion (21.9%). Among of all proteins, we selected three differential proteins (hnRNPC1/C2, NPM, and PSMA5), which were associated with the p53 pathway. Down-regulation of hnRNPC1/C2 and NPM contributed to the enhancement of phosphorylated p53. Activated p53 and down-regulation of PSMA5 resulted in an increase in p21 protein. Further studies showed that NB/Cur induced reactive oxygen species (ROS) generation, indicating that ROS might be upstream of the G2/M arrest signaling pathway. In summary, the results exhibited the whole proteomic response of HepG2 cells to NB/Cur, which might lead to a better understanding of its underlying anticancer mechanisms.

Asunto(s)

Canfanos/farmacología , Curcumina/farmacología , Puntos de Control de la Fase G2 del Ciclo Celular/efectos de los fármacos , Puntos de Control de la Fase M del Ciclo Celular/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Antineoplásicos , Apoptosis , Ciclo Celular , Células Hep G2 , Humanos , Proteómica , Transducción de Señal/fisiología

RESUMEN

Objective&Methods The mutagenicity of natural Borneol and synthetic Borneol was studied by using Ames test.Results Natural Borneol and Synthetic Borneol in the dose range of 0.4～250.0 ?g/plate had no effect in reducing the reversion frequencies of Salmonella Typhimurium histidine auxotrophic mutant(TA97,TA98,TA100,TA102)whether if metabolic activation system(S9mix)existed or not.Moreover,the backward mutant colony had normal background.Conclusion Natural Borneol and Synthetic Borneol do not possess evident mutagenicity under experimental condition.