Comparative Gene Signature of (-)-Oleocanthal Formulation Treatments in Heterogeneous Triple Negative Breast Tumor Models: Oncological Therapeutic Target Insights.
Comparative Gene Signature of (-)-Oleocanthal Formulation Treatments in Heterogeneous Triple Negative Breast Tumor Models: Oncological Therapeutic Target Insights.
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DOI：
10.3390/nu13051706
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发表时间：
2021-05-18
期刊：
影响因子：
5.9
通讯作者：
El Sayed KA
中科院分区：
文献类型：
--
作者：
Qusa MH;Abdelwahed KS;Siddique AB;El Sayed KA
三阴性乳腺癌（TNBC）异质性和有限的治疗选择赋予其表型侵袭性。具有有效分子靶标和确定的药效学特征的抗TNBC天然产物的发现将促进TNBC患者对它们的治疗性营养药物使用。特级初榨橄榄油（EVOO）是地中海饮食的关键成分。S-（−）-Oleocanthal（OC）是EVOO中具有抗肿瘤活性的酚类成分。先前的研究报道了用（+）-木糖醇配制的OC（OC-X）的固体分散体抑制TNBC MDA-MB-231细胞的体内进展和复发。本研究利用晚期临床前转基因MMTV-PyVT和TNBC PDX小鼠模型研究了OC-X制剂抑制体内异质性BC起始和进展的能力。此外，通过Clariom S微阵列分析获得的用OC-X处理的MMTV-PyVT和PDX小鼠肿瘤中的基因表达谱的聚类鉴定了明显受影响的基因。几个受影响的新特征基因在对OC-X治疗的反应中被鉴定出来，并在小鼠和人类肿瘤模型中被证明是重叠的，这为理解OC抗癌分子机制和帮助预测前瞻性临床结果提供了一些线索。这项研究提供了OC-X作为营养药物抑制异质性TNBC模型的潜力的分子和临床前证据，并提供了初步的基因水平治疗机制见解。
Triple negative breast cancer (TNBC) heterogeneity and limited therapeutic options confer its phenotypic aggressiveness. The discovery of anti-TNBC natural products with valid molecular target(s) and defined pharmacodynamic profile would facilitate their therapeutic nutraceutical use by TNBC patients. The extra-virgin olive oil (EVOO) is a key Mediterranean diet ingredient. S-(−)-Oleocanthal (OC) leads the bioactive anti-tumor EVOO phenolic ingredients. A previous study reported the solid dispersion formulated OC with (+)-xylitol (OC-X) suppressed the in vivo progression and recurrence of the TNBC MDA-MB-231 cells. This study investigates the ability of OC-X formulation to suppress the in vivo heterogeneous BC initiation and progression utilizing advanced preclinical transgenic MMTV-PyVT and TNBC PDX mouse models. Furthermore, the clustering of the gene expression profiles in MMTV-PyVT and PDX mouse tumors treated with OC-X acquired by a Clariom S microarray analysis identified the distinctly affected genes. Several affected novel signature genes identified in response to OC-X treatments and proved overlapped in both mouse and human tumor models, shedding some lights toward understanding the OC anticancer molecular mechanism and assisting in predicting prospective clinical outcomes. This study provides molecular and preclinical evidences of OC-X potential as a nutraceutical suppressing heterogeneous TNBC model and offers preliminary gene-level therapeutic mechanistic insights.
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影响因子：
9
作者：
Hamam R;Hamam D;Alsaleh KA;Kassem M;Zaher W;Alfayez M;Aldahmash A;Alajez NM
通讯作者：
Alajez NM
DOI：
10.3390/foods9111592
发表时间：
2020-11-02
期刊：
Foods (Basel, Switzerland)
影响因子：
--
作者：
Ahuja V;Macho M;Ewe D;Singh M;Saha S;Saurav K
通讯作者：
Saurav K
影响因子：
3.7
作者：
Akl MR;Ayoub NM;Mohyeldin MM;Busnena BA;Foudah AI;Liu YY;Sayed KA
通讯作者：
Sayed KA
影响因子：
5.5
作者：
Fallah Y;Brundage J;Allegakoen P;Shajahan-Haq AN
通讯作者：
Shajahan-Haq AN
影响因子：
7.5
作者：
Gaston K;Tsitsilianos MA;Wadey K;Jayaraman PS
通讯作者：
Jayaraman PS