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1.
Medicine (Baltimore) ; 99(34): e21952, 2020 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-32846865

RESUMEN

BACKGROUND: Sodium cantharidinate/vitamin B6 (SC/VB6) injection, a famous insect-derived traditional Chinese medicine preparation, has been widely applied as a promising adjunctive drug for hepatocellular carcinoma (HCC). However, its exact clinical efficacy and safety is still not well investigated. In this study, we aimed to summarize the efficacy of SC/VB6 injection on survival, liver function, immune function, and quality of life (QoL) in patients with HCC through the meta-analysis. METHODS: All available randomized controlled trials (RCTs) and high-quality prospective cohort studies that investigated the efficacy and safety of SC/VB6 for patients with HCC were searched from ten electronic databases including PubMed, Google Scholar, Cochrane Library, Excerpt Medica Database (Embase), Medline, Web of Science (WOS), Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), China Scientific Journal Database (CSJ), and Wanfang Database. Papers in Chinese or English published from January 2000 to July 2020 will be included without any restrictions.Study selection and data extraction will be performed independently by 2 researchers. The clinical outcomes including overall survival (OS), QoL, liver function, immune function, and adverse events, were systematically evaluated. Review Manager 5.3 and Stata 14.0 were used for data analysis, and the quality of the clinical trials was also evaluated. RESULTS: The results of this study will be published in a peer-reviewed journal, and provide a helpful evidence for clinicians to formulate the best postoperative adjuvant treatment strategy for HCC patients. CONCLUSION: Our study will draw an objective conclusion of the efficacy of SC/VB6 on survival, liver function, immune function, and QoL in patients with HCC. INPLASY REGISTRATION NUMBER: INPLASY202070121.


Asunto(s)
Cantaridina/análogos & derivados , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/patología , Vitamina B 6/farmacología , Complejo Vitamínico B/farmacología , Cantaridina/administración & dosificación , Cantaridina/farmacología , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/psicología , China/epidemiología , Quimioterapia Combinada/métodos , Humanos , Sistema Inmunológico/efectos de los fármacos , Inyecciones/métodos , Hígado/efectos de los fármacos , Medicina Tradicional China/métodos , Estudios Prospectivos , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Seguridad , Sobrevida , Resultado del Tratamiento , Vitamina B 6/administración & dosificación , Complejo Vitamínico B/administración & dosificación , Metaanálisis como Asunto
2.
Zhongguo Zhong Yao Za Zhi ; 41(15): 2824-2829, 2016 Aug.
Artículo en Chino | MEDLINE | ID: mdl-28914023

RESUMEN

To investigate the stability and the conversion rules of cantharidin and cantharidic acid contained in the Mylabris aqueous solution under different conditions. The contents of cantharidin and cantharidic acid under different conditions (pH, temperature and light) were determined by HPLC-TQ-MS. The results showed that the content of cantharidin was gradually decreased with the rising of pH value, while on the contrary, the content of cantharidic acid was increased gradually; after Mylabris aqueous solution with different pH values were placed at 25, 40 ℃ and 25 ℃ respectively for lighting for 90 days, the samples were collected for analysis. The results showed the contents of cantharidin and cantharidic acid were changed greatly in the first 10 days, mainly including the decrease of cantharidic acid and increase of cantharidin when the solution was acidic, and the increase of cantharidic acid and decrease of cantharidin when the solution was alkaline. After that, the contents of the above two components basically remained stable. This study revealed that pH was the main factor to affect the contents of cantharidin and cantharidic acid, and they could be converted into each other with the changes of pH value. High temperature and light can accelerate the speed of achieving such balance. The study can provide certain reference for the quality control of the medicines using the Mylabris as raw material.


Asunto(s)
Cantaridina/análogos & derivados , Cantaridina/química , Escarabajos/química , Animales , Cromatografía Líquida de Alta Presión , Concentración de Iones de Hidrógeno , Luz , Espectrometría de Masas , Temperatura
3.
Artículo en Inglés | MEDLINE | ID: mdl-24653566

RESUMEN

BACKGROUND: [corrected] Cantharidin, and its derivatives can not only inhibit the proliferation of tumor cells, but can also induce tumor cell apoptosis. It shows cantharidin exhibits a wide range of reactivity in anticancer. The objective of this paper was to study the inhibitory effect of sodium cantharidinate on human hepatoma HepG2 cells. MATERIALS AND METHODS: MTT assay was used to detect the proliferation of HepG2 cells, and immunohisto-chemical method was used to detect the change in VEGF, protein level, and to determine the inhibitory effect of sodium cantharidinate on human hepatoma HepG2 cells. RESULTS: As results, sodium cantharidinate significantly inhibited the growth of HepG2 cells in a time-and dose-dependent manner. CONCLUSION: We conclude that sodium cantharidinate has an inhibitory effect on human hepatoma HepG2 cells.


Asunto(s)
Antineoplásicos/uso terapéutico , Cantaridina/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Escarabajos/química , Neoplasias Hepáticas/tratamiento farmacológico , Animales , Antineoplásicos/farmacología , Apoptosis , Cantaridina/análogos & derivados , Cantaridina/farmacología , Proliferación Celular , Relación Dosis-Respuesta a Droga , Células Hep G2 , Humanos , Sodio
4.
Am J Chin Med ; 41(3): 665-82, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23711148

RESUMEN

Norcantharidin (NCTD) is currently used for anticancer therapy but the exact mechanism of action remains unknown. Pre-replicative complexes (pre-RCs) are essential for cell DNA replication and highly related to malignant proliferation. Here, we examined the inhibitory effect of NCTD on pre-RC components in HepG2 cells. We showed that NCTD induced degradation of Cdc6 and Mcm2 in a dose-dependent manner. Under 100 µM NCTD concentration, about 70% of Cdc6 and 50% of Mcm2 were degraded. In addition, the nuclear translocation of Mcm6 was inhibited by NCTD. Further studies aiming at G1 synchronous cells showed that, NCTD reduced the chromatin-bound Cdc6, Mcm2 and Mcm6. Moreover, the cells were blocked from entering the S phase and accumulated at the G1 phase when released synchronously into the cell cycle. Consistently, the DNA replication was inhibited by NCTD. Finally, the combination NCTD with Cdc6 depletion lead to more severe cytotoxicity (88%) than NCTD (52%) and Cdc6 depletion (39%) alone. A synergic cytotoxicity was observed between Cdc6 depletion and NCTD. In conclusion, our results demonstrate that NCTD inhibits pre-RC assembly; subsequently blocks the G1 to S transition; and inhibits DNA replication in HepG2 cells. Pre-RCs are an intriguing target for cancer therapy, which merits further investigations for anticancer development.


Asunto(s)
Antineoplásicos/uso terapéutico , Compuestos Bicíclicos Heterocíclicos con Puentes/uso terapéutico , Proteínas de Ciclo Celular/metabolismo , Ciclo Celular/efectos de los fármacos , Replicación del ADN/efectos de los fármacos , Neoplasias Hepáticas/tratamiento farmacológico , Proteínas Nucleares/metabolismo , Antineoplásicos/farmacología , Transporte Biológico , Compuestos Bicíclicos Heterocíclicos con Puentes/farmacología , Cantaridina/análogos & derivados , Cantaridina/farmacología , Cantaridina/uso terapéutico , Núcleo Celular/efectos de los fármacos , Cromatina/metabolismo , Células Hep G2 , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Componente 2 del Complejo de Mantenimiento de Minicromosoma , Componente 6 del Complejo de Mantenimiento de Minicromosoma
5.
Curr Med Chem ; 20(2): 159-66, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23210849

RESUMEN

This review summarizes the progress that has been made recently in the medicinal chemistry of cantharidin, a potent antitumor agent from traditional Chinese medicine. Thousands of analogs have been synthesized on the basis of cantharidin, a part of which shows excellent properties, in particular, norcantharidin and norcantharimide. Despite the enormous efforts made, the intriguing bioactivities, mechanism, indications, and their interplay are still ill-defined. This review provides our up-to-date understanding in connection with the therapeutic use, mechanism, structure-activity relationship (SAR) and interesting properties of cantharidin analogs. Considerable development in the design of cantharidin analogs, in combination with mechanistic studies, has laid a foundation for transforming novel antitumor drugs into the clinic.


Asunto(s)
Antineoplásicos/uso terapéutico , Cantaridina/uso terapéutico , Neoplasias/tratamiento farmacológico , Antineoplásicos/síntesis química , Antineoplásicos/química , Cantaridina/análogos & derivados , Cantaridina/química , Humanos , Medicina Tradicional China/tendencias
6.
Zhong Yao Cai ; 34(3): 343-6, 2011 Mar.
Artículo en Chino | MEDLINE | ID: mdl-21823448

RESUMEN

OBJECTIVE: To study the effect of sodium cantharidinate on the angiogenesis of nude mice with human gastric cancer. METHODS: Nude mice xenograft models of human gastric cancer were established by injecting gastric carcinoma cell BGC823 into peritoneal. Expression of VEGF and MVD labeling by CD34 in human gastric cancer cells were measured by immunohistochemistry. RESULTS: Expression scores of VEGF in medium dose and high dose group with sodium cantharidinate treatment were lower than those in low dose and control group (P < 0.01). There was no significant difference between medium dose and high dose group or low dose and control group (P > 0.05). MVD values in medium and high dose group with sodium cantharidinate treatment were lower than those in low dose and control group (P < 0.01), but there was no significant difference between medium dose and high dose group (P > 0.05). CONCLUSIONS: sodium cantharidinate can inhibit the growth of the tumor by down-regulating VEGF expression of the tumour cell and the angiogenesis of the tumour.


Asunto(s)
Cantaridina/análogos & derivados , Materia Medica/farmacología , Neovascularización Patológica/prevención & control , Neoplasias Gástricas/patología , Factores de Crecimiento Endotelial Vascular/metabolismo , Animales , Antineoplásicos/administración & dosificación , Antineoplásicos/farmacología , Cantaridina/administración & dosificación , Cantaridina/farmacología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Inmunohistoquímica , Materia Medica/administración & dosificación , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Microvasos , Trasplante de Neoplasias , Neoplasias Gástricas/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto
7.
Zhongguo Zhong Yao Za Zhi ; 35(19): 2613-5, 2010 Oct.
Artículo en Chino | MEDLINE | ID: mdl-21174776

RESUMEN

OBJECTIVES: To establish a HPLC method for determination of N-methylcantharidimide in dogs' plasma and to study the pharmacokinetics of N-methylcantharidimide in dogs'. METHOD: The plasma samples were extracted by methanol. The acetonitrile and the purified water composed mobile phase. The flow rate was 0. 7 mL x min(-1), ultraviolet detection wavelength was at 212 nm. RESULT: The calibration curve was linear over the range from 0.01-10.0 mg x L(-1) with a correlation coefficiency of 0.996 3. The lower limit of quantitation was 0.01 mg x L(-1). The mean recovery was 92.3%. the relative standard deviation (RSD) of intra-day and inter-day were all less than 10%. After intravenous administration of N-methylcantharidimide with 3 dosages of 10, 15, 20 mg x kg(-1) to dogs, the corresponding distribution half-livers (t1/2alpha) were 1.8, 2.1, 1.7 min, and the elimination half-lives (t1/2beta) were 144,139, 146 min, respectively. CONCLUSION: This method is convenient, accurate and reliable. It can be used for determination of N-methylcantharidimide in dogs' plasma and pharmacokinetic studies.


Asunto(s)
Cantaridina/análogos & derivados , Cromatografía Líquida de Alta Presión/métodos , Isoindoles/sangre , Animales , Área Bajo la Curva , Cantaridina/administración & dosificación , Perros , Femenino , Isoindoles/administración & dosificación , Masculino
8.
Cancer Lett ; 223(2): 227-37, 2005 Jun 08.
Artículo en Inglés | MEDLINE | ID: mdl-15896457

RESUMEN

A novel series of TCM-platinum complexes [Pt(C8H8O5)(NH2R)2] 1-5, designed from incorporating demethylcantharidin, a modified component from a traditional Chinese medicine (TCM) with a platinum moiety was found to circumvent cisplatin resistance in mouse leukemia and human hepatocellular carcinoma. These properties are most likely due to the inclusion of the protein phosphatase 2A (PP2A)-inhibiting demethylcantharidin in the novel compounds. We have investigated the potential synergistic effect of combining demethylcantharidin with a platinum-based antitumor agent, such as cisplatin, carboplatin, or oxaliplatin in vitro against L1210 mouse leukemia and SK-Hep-1 human hepatocellular carcinoma, and in vivo against a SK-Hep-1 subcutaneous-inoculated xenograft in nude mice, using median effect analysis. Demethylcantharidin and the platinum antitumor agents were synergistic in all cell lines tested in vitro, and the most effective antiproliferative regimen was when demethylcantharidin was added 24 h before cisplatin. Synergistic antitumor activity was also demonstrated in vivo without undue toxicity; no excessive loss in mouse body weight or overt pathology were observed at the effective doses. The results support a new approach for augmenting cytotoxic effect of established Pt-based drugs with demethylcantharidin in treating human hepatocellular carcinoma and other solid tumors.


Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Cantaridina/análogos & derivados , Cantaridina/farmacología , Carboplatino/farmacología , Cisplatino/farmacología , Compuestos Organoplatinos/farmacología , Animales , Apoptosis , Peso Corporal , Carcinoma Hepatocelular/patología , Interacciones Farmacológicas , Humanos , Leucemia/patología , Neoplasias Hepáticas/patología , Ratones , Ratones Desnudos , Oxaliplatino , Células Tumorales Cultivadas/patología
9.
Bioorg Med Chem ; 12(17): 4565-73, 2004 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-15358284

RESUMEN

Novel TCM-platinum compounds [Pt(C(8)H(8)O(5))(NH(2)R)(2)] 1-5, derived from integrating demethylcantharidin, a modified component from a traditional Chinese medicine (TCM) with a platinum moiety, possess anticancer and protein phosphatase 2A inhibition properties. The compounds are able to circumvent cisplatin resistance by apparently targeting the DNA repair mechanism. Novel isosteric analogues [Pt(C(9)H(10)O(4))(NH(2)R)(2)] A and B, devoid of PP2A-inhibitory activity, were found to suffer from an enhanced DNA repair and were cross-resistant to cisplatin. The results advocate a well-defined structure-activity requirement associating the PP2A-inhibiting demethylcantharidin with the circumvention of cisplatin cross-resistance demonstrated by TCM-Pt compounds 1-5.


Asunto(s)
Antineoplásicos Fitogénicos/síntesis química , Cantaridina/análogos & derivados , Cisplatino/análogos & derivados , Resistencia a Antineoplásicos/efectos de los fármacos , Compuestos Organoplatinos/síntesis química , Fosfoproteínas Fosfatasas/antagonistas & inhibidores , Antineoplásicos Fitogénicos/farmacología , Cantaridina/farmacología , Cisplatino/farmacología , Reactivos de Enlaces Cruzados/síntesis química , Reparación del ADN/efectos de los fármacos , Inhibidores Enzimáticos/farmacología , Femenino , Humanos , Masculino , Medicina Tradicional China , Compuestos Organoplatinos/farmacología , Proteína Fosfatasa 2 , Relación Estructura-Actividad , Factores de Tiempo , Células Tumorales Cultivadas
10.
Chem Pharm Bull (Tokyo) ; 52(7): 807-9, 2004 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-15256700

RESUMEN

Three novel cantharidin analogues were isolated from the Chinese blister beetle, Mylabris phalerata PALL. (Meloidae), which has been used in traditional Chinese medicine for the treatment of cancer. Their structures were determined on the basis of heteronuclear multiple-bond connectivity and nuclear Overhauser effect spectroscopy experiments, and chemical data confirmed them to be so-called cantharimides, in which the anhydride oxygen atoms are replaced by the basic amino acid L-lysine, L-ornithine, and L-arginine moieties.


Asunto(s)
Cantaridina/análogos & derivados , Cantaridina/química , Cantaridina/aislamiento & purificación , Escarabajos , Medicina Tradicional China , Animales
11.
J Chromatogr A ; 947(2): 319-26, 2002 Feb 22.
Artículo en Inglés | MEDLINE | ID: mdl-11885572

RESUMEN

The present paper describes the development of a simple, accurate and reproducible gas chromatographic method for the determination of hydrolyzed demethylcantharidin release from a novel series of traditional Chinese medicine (TCM)-platinum compounds possessing potent anticancer and protein phosphatase 2A (PP2A)-inhibition properties. The salient features of the validated assay were a limit of detection (LOD) of 2 microg/mL, a limit of quantitation (LOQ) of 6 microg/mL, an intra- and inter-day precision of less than 11%, and an accuracy of more than 92%. The developed GC-flame ionization detection (FID) method was successfully utilized for the analysis of hydrolyzed demethylcantharidin, the TCM component that is slowly released from the novel compounds over 24 h, leading to PP2A inhibition. Further structural confirmation was achieved by GC-MS. The GC method is suitable for further mechanistic, pharmacokinetic and metabolic studies of the TCM-Pt compounds that might prove to be new anticancer agents with novel mechanisms of cytotoxic action.


Asunto(s)
Cantaridina/farmacocinética , Medicina Tradicional China , Cantaridina/análogos & derivados , Cromatografía de Gases y Espectrometría de Masas , Hidrólisis , Reproducibilidad de los Resultados , Sensibilidad y Especificidad
12.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 19(1): 37-9, 1999 Jan.
Artículo en Chino | MEDLINE | ID: mdl-11783259

RESUMEN

OBJECTIVE: To certify the anti-tumor effects of the four Cantharidine derivatives and platinum complex on transplanted tumor in mice to search for new anti-tumor drugs. METHODS: Complex of four Cantharidine derivatives (Dpt 1-15, Dpt 5-10, Dpt 12-3 and Dpt6-2) and platinum were given to tumor beating mice of transplanted S180 sarcoma, H22 solid hepatocarcinoma and ascites hepatocarcinoma through intraperitoneal or intravenous injection, and the effect of treatment on tumor weight and survival of animal were observed. Cisplatin was used as positive control and 0.9% normal saline used as negative control. All data were treated with t test. RESULTS: All the four complex had anti-tumor effect. The inhibition rate of Dpt5-10 and Dpt1-15 on S180 sarcoma and H22 solid hepatocarcinoma and the survival prolongation rate of Dpt5-10 on H22 ascites hepatocarcinoma were similar to those of cisplatin. The toxicity of effective dose of Dpt1-15 was rather high. CONCLUSIONS: Cantharidine derivatives and platinum complex is new effective anti-tumor drug, among them the Dpt5-10 is the most effective one. Further study for improving the solubility of drug is necessary and study the difference of cross resistance between the new complex and cisplatinum.


Asunto(s)
Antineoplásicos/farmacología , Cantaridina/farmacología , Compuestos Organoplatinos/farmacología , Sarcoma 180/tratamiento farmacológico , Animales , Cantaridina/análogos & derivados , Femenino , Neoplasias Hepáticas Experimentales/tratamiento farmacológico , Masculino , Ratones , Trasplante de Neoplasias
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