作者：
Bu, Yiwen;Cai, Guoshuai;Shen, Yi;Huang, Chenfei;Zeng, Xi;...
期刊：
Cancer Letters,2016年383(2):261-271 ISSN：0304-3835
通讯作者：
Cao, Deliang;Liao, Duan-Fang
作者机构：
[Huang, Chenfei; Shen, Yi; Cao, Yu; Bu, Yiwen; Cao, Deliang] Southern Illinois Univ, Sch Med, Simmons Canc Inst, Dept Med Microbiol Immunol & Cell Biol, 913 N Rutledge St, Springfield, IL 62794 USA.;[Cai, Guoshuai] Geisel Sch Med Dartmouth, Dept Genet, Hanover, NH 03755 USA.;[Zeng, Xi] Univ South China, Canc Res Inst, Hengyang 421001, Hunan, Peoples R China.;[Wang, Yuhong; Cao, Deliang; Huang, Dan; Liao, Duan-Fang; Cai, Chuan] Hunan Univ Chinese Med, State Key Lab Chinese Med Powder & Med Innovat Hu, Div Stem Cell Regulat & Applicat, Changsha 410208, Hunan, Peoples R China.;[Liao, Duan-Fang] Hunan Univ Tradit Chinese Med, Div Stem Cell Regulat & Applicat, 1 Xiangzui Rd, Changsha 410208, Hunan, Peoples R China.
通讯机构：
[Cao, Deliang] S;[Liao, Duan-Fang] H;Southern Illinois Univ, Sch Med, Simmons Canc Inst, Dept Med Microbiol Immunol & Cell Biol, 913 N Rutledge St, Springfield, IL 62794 USA.;Hunan Univ Tradit Chinese Med, Div Stem Cell Regulat & Applicat, 1 Xiangzui Rd, Changsha 410208, Hunan, Peoples R China.
关键词：
NF-kappa B RelA/p65;ABCC6;RITA;Chemoresistance
摘要：
Inactivation of p53 occurs frequently in various cancers. RITA is a promising anticancer small molecule that dissociates p53-MDM2 interaction, reactivates p53 and induces exclusive apoptosis in cancer cells, but acquired RITA resistance remains a major drawback. This study found that the site-differential phosphorylation of nuclear factor-kappa B (NF-kappa B) RelA/p65 creates a barcode for RITA chemosensitivity in cancer cells. In naive MCF7 and HCT116 cells where RITA triggered vast apoptosis, phosphorylation of RelA/p65 increased at Ser536, but decreased at Ser276 and Ser468; oppositely, in RITA-resistant cells, RelA/p65 phosphorylation decreased at Ser536, but increased at Ser276 and Ser468. A phosphomimetic mutation at Ser536 (p65/S536D) or silencing of endogenous RelA/p65 resensitized the RITA-resistant cells to RITA while the phosphomimetic mutant at Ser276 (p65/S276D) led to RITA resistance of naive cells. In mouse xenografts, intratumoral delivery of the phosphomimetic p65/S536D mutant increased the antitumor activity of RITA. Furthermore, in the RITA-resistant cells ATP-binding cassette transporter ABCC6 was upregulated, and silencing of ABCC6 expression in these cells restored RITA sensitivity. In the naive cells, ABCC6 delivery led to RITA resistance and blockage of p65/S536D mutant-induced RITA sensitivity. Taken together, these data suggest that the site-differential phosphorylation of RelA/p65 modulates RITA sensitivity in cancer cells, which may provide an avenue to manipulate RITA resistance. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
摘要：
BACKGROUND: Angelica sinensis and Aurantii fructu used in a pair, named Danggui-Zhiqiao herb-pair (DZHP), which was rich in essential oil and has been adopted to promote blood circulation, dispel blood stasis, and relieve pain in traditional Chinese medicine (TCM). OBJECTIVE: To analyze the composition and pharmacological effects of essential oil from DZHP. MATERIALS AND METHODS: The composition of the essential oil from DZHP was analyzed by gas chromatography/mass spectrometry (GC/MS). Its analgesic activity was evaluated by acetic acid-induced writhing test and hot plate test. The hemorheology test was carried out to evaluate the effect on hemorheology in rats with blood stasis syndrome. RESULTS: Twenty-eight components were identified and the main components were alpha-pinene (3.07%), beta-pinene (2.0%), beta-myrcene (3.71%), D-limonene (49.28%), gamma-terpinen (9.53%), alpha-terpinolene (1.80%), alpha-terpineol (2.02%), beta-bisabolene (1.13%), butylidenephthalide (1.43%), and Z-ligustilide (16.08%). The pharmacology test showed that the essential oil significantly inhibited the number of writhes induced by acetic acid with inhibition rate of 44.64% and significantly increased hot-plate latency compared with control group from 30 to 90 min after oral administration of drugs in mice. It could significantly decrease plasma viscosity, whole blood relative index at high and low shear rate, whole blood reduced viscosity at high and low shear rate, and erythrocyte rigidity index in hemorheology test. CONCLUSION: The composition of the essential oil of DZHP was determined successfully and it had analgesic and promoting blood circulation activities. SUMMARY: Angelica sinensis and Aurantii fructu used in a pair, named Danggui-Zhiqiao herb-pair (DZHP), which was rich in Essential oil and has been adopted to promote blood circulation, dispel blood stasis and relieve pain in traditional Chinese medicine (TCM).Twenty-eight components were identified and the main components were alpha-pinene (3.07%), beta-pinene (2.0%), beta-myrcene (3.71%), D-limonene (49.28%), gamma-terpinen (9.53%), alpha-terpinolene (1.80%), alpha-terpineol (2.02%), beta-bisabolene (1.13%), butylidenephthalide (1.43%), and Z-ligustilide (16.08%).The essential oil significantly inhibited the number of writhes induced by acetic acid and increased hot-plate latency compared with control group from 30 min to 90 min after oral administration of drugs in mice.The essential oil could significantly decrease plasma viscosity (PV), whole blood relative index (WBRI) at high and low shear rate, whole blood reduced viscosity (WBRV) at high and low shear rate, and erythrocyte rigidity index (ERI) in hemorheology test. Abbreviations used: DZHP: Danggui-Zhiqiao herb-pair; TCM: traditional Chinese medicine; GC/MS: gas chromatography /mass spectrometry; PV: plasma viscosity; WBRI: whole blood relative index; WBRV: whole blood reduced viscosity; ERI: erythrocyte rigidity index.
摘要：
To assess the extraction methods of egg yolk oil in ShiZhenKang (SZK) oil, which is used to treat eczema, a mice model of eczema was established by using 2,4-dinitrochlorobenzene (DNCB). The therapeutic effects of egg yolk oil extracted by different methods from SZK oil on the model of acute eczema in mice were evaluated. The oil yield rate of ethanol extraction is 42.06%. Its egg yolk oil is orange and has a rich, sweet, egg smell. Moreover, the SZK oil prepared from it has a very good therapeutic effect on the model of acute eczema in mice. The alcohol extraction method is the preferable method according to a comprehensive evaluation of each index of seven kinds of methods to extract the egg yolk oil.
期刊：
Cancer Letters,2016年372(2):219-225 ISSN：0304-3835
通讯作者：
Zhang, Xuewen;Cao, Deliang
作者机构：
[Cao, Zhe; Zhang, Xuewen; Cao, Deliang] Hunan Agr Univ, Coll Biosci & Biotechnol, Changsha 410128, Hunan, Peoples R China.;[Zhou, Boping; Cao, Zhe; Chen, Xinchun] Shenzhen Third Peoples Hosp, Guangdong Med Coll, Shenzhen Key Lab Infect & Immun, Shenzhen, Peoples R China.;[Ma, Jun; Cao, Deliang] So Illinois Univ, Sch Med, Dept Med Microbiol Immunol & Cell Biol, Simmons Canc Inst, 913 N Rutledge St, Springfield, IL 62794 USA.;[Cao, Deliang; Huang, Dan; Cai, Chuan] Hunan Univ Chinese Med, Div Stem Cell Regulat & Applicat, State Key Lab Chinese Med Powder & Med Innovat Hu, Changsha 410208, Hunan, Peoples R China.
通讯机构：
[Zhang, XW; Cao, DL; Cao, Deliang] H;[Cao, Deliang] S;Hunan Agr Univ, Coll Biosci & Biotechnol, Changsha 410128, Hunan, Peoples R China.;So Illinois Univ, Sch Med, Dept Med Microbiol Immunol & Cell Biol, Simmons Canc Inst, 913 N Rutledge St, Springfield, IL 62794 USA.;Hunan Univ Chinese Med, Div Stem Cell Regulat & Applicat, State Key Lab Chinese Med Powder & Med Innovat Hu, Changsha 410208, Hunan, Peoples R China.
关键词：
Uridine phosphorylase;UPase knockout;Uridine homeostasis;p53;Uracil DNA damage;Carcinogenesis
摘要：
Uridine is a natural nucleoside precursor of uridine monophosphate in organisms and thus is considered to be safe and is used in a wide range of clinical settings. The far-reaching effects of pharmacological uridine have long been neglected. Here, we report that the homeostatic disorder of uridine is carcinogenic. Targeted disruption (-/-) of murine uridine phosphorylase (UPase) disrupted the homeostasis of uridine and increased spontaneous tumorigenesis by more than 3-fold. Multiple tumors (e.g., lymphoma, hepatoma and lung adenoma) occurred simultaneously in some UPase deficient mice, but not in wild-type mice raised under the same conditions. In the tissue from UPase-/- mice, the 2'-deoxyuridine,5'-triphosphate (dUTP) levels and uracil DNA were increased and p53 was activated with an increased phospho-Ser18 p53 level. Exposing cell lines (e.g., MCF-7, RKO, HCT-8 and NCI-H460) to uridine (10 or 30 mu M) led to uracil DNA damage and p53 activation, which in turn triggered the DNA damage response. In these cells, phospho-ATM, phospho-CHK2, and phospho-gamma H2AX were increased by uridine. These data suggest that uridine homeostatic disorder leads to uracil DNA damage and that pharmacological uridine may be carcinogenic. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
摘要：
Background: Bushen Huoxue Qubi (BHQ) granules, a traditional Chinese medicine preparation, has been clinically used for the treatment of the blood stasis syndrome. Objective: The main objective is to investigate whether the diseased condition would alter the pharmacokinetics and tissue distribution of tanshinone IIA in BHQ, which was given orally to the acute blood stasis rats. Materials and Methods: The main bioactive constituent in BHQ, tanshinone IIA, was measured in the plasma and tissues of animals by the high performance liquid chromatography with ultraviolet detection. The analysis was successfully performed on an Agilent TC-C-18 column (250 x 4.6 mm I.D., 5 mu m) protected with a Octadecylsilane (ODS) guard column (10 x 4.6 mm I.D., 5 mu m). The mobile phase was aqueous solution (A) (containing 0.40% aqueous acetic acid) and acetonitrile (B). The conditions of the solvent gradient elution were 35-40% (B) in 0-15 min, 40-42% (B) in 15-18 min and 42-70% (B) in 18-30 min at a flow rate of 1.0 mL/min. Detection was conducted with wavelength of 270 nm at 30 degrees C. Results: Good linearity relationships were found (r(2) > 0.9955) over the investigated concentration range for bio-samples. Blood stasis was associated with significantly higher area under the concentration-time curve (AUC), the maximum plasma concentration (C-max) and biological half-life (t(1/2)), lower total body clearance (CL) and apparent volume of distribution (Vd) of tanshinone IIA in plasma and higher AUC(0-t) of tanshinone IIA in the analyzed tissues of rats treated with BHQ. Conclusion: Blood stasis could alter pharmacokinetics and tissue distribution of tanshinone IIA in BHQ.
