Search

Aim: Resistance to platinum-based therapeutic agents is the major contributor to epithelial ovarian cancer (EOC) mortality. There is an urgent need to better understand the underlying mechanisms. Here we investigated the role of serpins in EOC chemoresistance and related mechanisms, and found that SERPINE1 played an important role in chemoresistance in A2780cp cells.Materials and Methods: A2780cp and A2780s cells were used in our study. Microarray screening was used to identify the gene expression change under carboplatin treatment. A cell-counting kit-8 was used to detect the sensitivity of ovarian cancer cells after treatment. The expression of SERPINE1 was silenced by siRNA. The levels of SERPINE1 and epithelial-mesenchymal transition (EMT)-related proteins were confirmed by Western blot. MassArray EpiTYPER quantitative DNA methylation analysis was introduced to evaluate the methylation of the promoter of SERPINE1.Results: Microarray data showed that SERPINE1 and SERPINE2 increased most dramatically under carboplatin treatment in A2780cp cells. Carboplatin treatment could significantly increase the expression of SERPINE1 and induce the EMT process, with decreased expression of E-cadherin and increased expression of Vimentin, Snail and Twist. Knockdown of SERPINE1, but not SERPINE2, in A2780cp cells could inhibit the EMT process. We also found that hypomethylation in the promoter of SERPINE1 might result in the increased expression of SERPINE1 and subsequent EMT process in A2780cp cells.Conclusion: Our study suggested that SERPINE1 may be a promising therapeutic target for chemoresistance. [ABSTRACT FROM AUTHOR]

In the current work, 12 novel 25-hydroxyprotopanaxadiol (25-OH-PPD) derivatives were synthesized by reacting with chloroacetyl chloride. And their in vitro antitumor activities were evaluated on six human tumor cell lines by MTT assay. The results demonstrated that, as compared with 25-OH-PPD, compounds 4 , 6 and 7 exhibited higher cytotoxic activity on all tested cell lines. Of them, compound 4 showed strongly inhibition against MCF-7, HCT-116 and Lovo cells with IC 50 values of 1.7, 1.6 and 2.1 μM, respectively. The IC 50 values of compound 6 against HCT-116 and 7 against MCF-7 were the lowest (1.2 and 1.6 μM, respectively). It was also noted that compound 4 showed a 20- to 100-fold greater growth inhibition than ginsenoside-Rg 3 (an anti-cancer regular drug in China). In conclusion, the data revealed that compounds 4 , 6 and 7 were potential candidates for anti-tumor treatment and may be useful for the development of novel antiproliferative agents. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) is a common gynecological endocrine and metabolic disorder. Chinese herbal medicine has some advantages in the treatment of PCOS with its unique theoretical system and rich clinical practice experiences. The present study was to investigate the potential mechanisms of Bu-Shen-Jian-Pi Formula (BSJPF) on the treatment of PCOS. The combination of ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS/MS) rapid analysis, network pharmacology, molecular docking analysis and bio-experiments were firstly conducted to identify the main effective components of BSJPF, and to predict the potential mechanisms. The ovarian granulosa cell line (KGN) was treated with testosterone to construct the PCOS model in vitro, and the cells were further treated with the lyophilized powder of BSJPF. The levels of proliferation, autophagy and apoptosis were detected to explore the mechanisms of BSJPF on treating PCOS. Firstly, thirty-six active compounds were identified in BSJPF and thirty-one potential targets on PCOS were found. Then, PI3K and PDK1 were verified to have good binding activity with the active compounds through molecular docking analysis. In bio-experiments, BSJPF significantly alleviated the arrested proliferation of KGN cells in G0/G1 phase and reduced the active levels of autophagy and apoptosis of KGN cells induced by testosterone. Additionally, the inhibition of autophagy diminished apoptosis, while the repression apoptosis enhanced autophagy. Finally, BSJPF significantly decreased the FOXO1 expression levels induced by testosterone, especially for nuclear FOXO1, and significantly activated the PI3K/AKT pathway. BSJPF significantly alleviated the activated autophagy and apoptosis in KGN induced by testosterone through PI3K/AKT1/FOXO1pathway, which is an effective treatment for PCOS. [Display omitted] [ABSTRACT FROM AUTHOR]

(20R)-Dammarane-3 β , 12 β , 20, 25-tetrol (25-OH-PPD) is a ginsenoside isolated from Panax ginseng (C. A. Meyer). This compound exhibits anti-cancer activities on many human cancer cell lines. In this study, we investigated anti-cancer mechanisms of 12 β - O -( L -Chloracetyl)-dammar-20(22)-ene-3 β ,25-diol(12-Chloracetyl-PPD), a modified 25-OH-PPD. We found that compound 12-Chloracetyl-PPD resulted in a concentration-dependent inhibition of viability in prostate, breast, and gastric cancer cells, without affecting the viability of normal cell (human gastric epithelial cell line-GES-1, hair follicle dermal papilla cell line-HHDPC and rat myocardial cell line-H9C2). In MDA-MB-435 and C4-2B cancer cells, 12-Chloracetyl-PPD induced G2/M cell cycle arrest, down-regulated mouse double minute 2 (MDM2) expression, up-regulated p53 expression, triggered apoptosis, and stimulated reactive oxygen species production. Apoptosis can be attenuated by the reactive oxygen species scavenger N-acetylcysteine. Our results suggested that compound 12-Chloracetyl-PPD showed obvious anti-cancer activity based on delaying cell cycle arrest and inducing cell apoptosis by reactive oxygen species production, which supported development of 12-Chloracetyl-PPD as a potential agent for cancer chemotherapy. [ABSTRACT FROM AUTHOR]

Platycladus orientalis (L.) Franco is traditionally known to potentiate hair growth promotion. However, there has been no report on its main active ingredient responsible for the hair growth activity. In the current work, cedrol as a major constituent from P. orientalis was evaluated for its potential on hair growth in vivo . Different concentrations of cedrol (10, 20 and 30 mg/mL) were applied topically over the shaved skin of C57BL/6 mice and monitored for 21 days. Results indicated that cedrol significantly promoted hair growth in a dose-dependent manner, particularly for the female mice. Both male and female mice groups treated with 30 mg/mL cedrol required shorter time than the blank control and 2% minoxidil groups at different growth stages. Compared with the blank control (8.87 mm) and 2% minoxidil (9.94 mm) groups at 21 days, the hair length of female mice treated with 30 mg/mL cedrol showed a remarkable increase with the value of 11.07 mm. Hair in male and female mice groups treated with 30 mg/mL cedrol was heavier than the 2% minoxidil (38.2 and 35.9 mg, respectively) groups with the weight of 42.6 and 45.2 mg, respectively. Further observation of the hair follicle demonstrated that cedrol exerted a remarkable effect on the hair follicle length. These findings suggested that cedrol may be the main active ingredient of P. orientalis and have the potential of becoming a new hair growth promoter. [ABSTRACT FROM AUTHOR]