scholarly journals Characterizing the Efficacy of Fermented Wheat Germ Extract Against Ovarian Cancer and Defining the Genomic Basis of Its Activity

2012 ◽  
Vol 22 (6) ◽  
pp. 960-967 ◽  
Author(s):  
Patricia L. Judson ◽  
Entidhar Al Sawah ◽  
Douglas C. Marchion ◽  
Yin Xiong ◽  
Elona Bicaku ◽  
...  

ObjectiveMost women with advanced-stage epithelial ovarian cancer (OVCA) ultimately develop chemoresistant recurrent disease. Therefore, a great need to develop new, more active, and less toxic agents and/or to optimize the efficacy of existing agents exists.MethodsIn this study, we investigated the activity of Avemar, a natural, nontoxic, fermented wheat germ extract (FWGE), against a range of OVCA cell lines, both alone and in combination with cisplatin chemotherapy and delineated the molecular signaling pathways that underlie FWGE activity at a genome-wide level.ResultsWe found that FWGE exhibited significant antiproliferative effects against 12 human OVCA cell lines and potentiated cisplatin-induced apoptosis. Pearson correlation of FWGE sensitivity and gene expression data identified 2142 genes (false discovery rate < 0.2) representing 27 biologic pathways (P< 0.05) to be significantly associated with FWGE sensitivity. A parallel analysis of genomic data for 59 human cancer cell lines matched to chemosensitivity data for 2,6-dimethoxy-p-benzoquinone, a proposed active component of FWGE, identified representation of 13 pathways common to both FWGE and 2,6-dimethoxy-p-benzoquinone sensitivity.ConclusionsOur findings confirm the value of FWGE as a natural product with anticancer properties that may also enhance the activity of existing therapeutic agents. Furthermore, our findings provide substantial insights into the molecular basis of FWGE’s effect on human cancer cells.Research HighlightsFermented wheat germ extract has significant antiproliferative effects on OVCA cell lines and may enhance the effect of cisplatin-induced cell death.Genome-wide expression data reveal that FWGE sensitivity in ovarian cancer cells was associated with 2142 genes, representing 27 biologic pathways.The known safety and tolerability of FWGE supports the clinical evaluation of this natural product in patients with ovarian cancer.

2018 ◽  
Vol 42 (6) ◽  
pp. e12688 ◽  
Author(s):  
Eun Mi Koh ◽  
Eun Kyeong Lee ◽  
Jeongah Song ◽  
Su Jin Kim ◽  
Chi Hun Song ◽  
...  

Nutrients ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 1546 ◽  
Author(s):  
Khrystyna Zhurakivska ◽  
Giuseppe Troiano ◽  
Vito Caponio ◽  
Mario Dioguardi ◽  
Claudia Arena ◽  
...  

Fermented wheat germ extract (FWGE; trade name AVEMAR) is a natural compound derived from industrial fermentation of wheat germ. Its potential anticancer properties has emerged from recent studies. The aim of this systematic review is to summarize the data available in the scientific literature concerning the in vitro activity of FWGE on malignant cells. A systematic review of English articles in electronic databases has been performed. The primary outcomes of the review regarded types of cancer cell lines subjected to the investigation and the main results concerning cell viability, proliferation, and apoptosis observed within the studies. Sixteen articles were included in the final qualitative analysis. Various types of cancer cells treated with FWGE have been analyzed, showing mainly cytotoxic effects, alteration of the cell cycle, antiproliferative effects, and induction of apoptosis. FWGE can be a promising drug component in cancer treatment; however, further in vitro and in vivo studies are necessary to prove its effectiveness and safety in humans.


2018 ◽  
Vol 475 (21) ◽  
pp. 3471-3492 ◽  
Author(s):  
Iru Paudel ◽  
Sean M. Hernandez ◽  
Gilda M. Portalatin ◽  
Tara P. Chambers ◽  
Jeremy W. Chambers

The occurrence of chemotherapy-resistant tumors makes ovarian cancer (OC) the most lethal gynecological malignancy. While many factors may contribute to chemoresistance, the mechanisms responsible for regulating tumor vulnerability are under investigation. Our analysis of gene expression data revealed that Sab, a mitochondrial outer membrane (MOM) scaffold protein, was down-regulated in OC patients. Sab-mediated signaling induces cell death, suggesting that this apoptotic pathway is diminished in OC. We examined Sab expression in a panel of OC cell lines and found that the magnitude of Sab expression correlated to chemo-responsiveness; wherein, OC cells with low Sab levels were chemoresistant. The Sab levels were reflected by a corresponding amount of stress-induced c-Jun N-terminal kinase (JNK) on the MOM. BH3 profiling and examination of Bcl-2 and BH3-only protein concentrations revealed that cells with high Sab concentrations were primed for apoptosis, as determined by the decrease in pro-survival Bcl-2 proteins and an increase in pro-apoptotic BH3-only proteins on mitochondria. Furthermore, overexpression of Sab in chemoresistant cells enhanced apoptotic priming and restored cellular vulnerability to a combination treatment of cisplatin and paclitaxel. Contrariwise, inhibiting Sab-mediated signaling or silencing Sab expression in a chemosensitive cell line resulted in decreased apoptotic priming and increased resistance. The effects of silencing on Sab on the resistance to chemotherapeutic agents were emulated by the silencing or inhibition of JNK, which could be attributed to changes in Bcl-2 protein concentrations induced by sub-chronic JNK inhibition. We propose that Sab may be a prognostic biomarker to discern personalized treatments for OC patients.


Author(s):  
SIVA JYOTHI BUGGANA ◽  
MANI CHANDRIKA PATURI ◽  
RAJENDRA PRASAD VVS

Objective: In this study, a series of novel 2,3-disubstituted quinazolines (4a-4l) were synthesized using standard procedures and elucidated through different spectroscopic techniques. Methods: Obtained compounds were evaluated for their cytotoxicity against human breast cancer (MDA-MB-231) and ovarian cancer (SK-O-V3) cell lines using MTT assay. Docking studies with JAK2 protein were performed to elucidate the possible mechanistic insights into these novel quinazoline derivatives. Results: Moderate-to-good in vitro cytotoxic potentials of the newly synthesized molecules were reported against selected human cancer cell lines. Among the tested molecules, compound 4e showed good cytotoxic activity against MD-AMB-231 (14.2 ± 0.86 μM) and against SK-O-V3 (17.7 ± 0.62 μM). Conclusion: The in vitro studies of the newly synthesized quinazoline derivatives reported considerable cytotoxic potentials against both breast and ovarian cancer cell lines and SAR studies suggest that quinazoline derivatives with heterocyclic benzothiazole nucleus with hydrophilic acetamide linkage at the 3rd position could probably increase the cytotoxic potentials and the presence of chlorine substitution could add more benefit. With the reported bioactivities of these derivatives, further studies on the derivatization could elucidate the broader cytotoxic potentials.


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