Molecular genomic features associated with in vitro response of the NCI-60 cancer cell line panel to natural products.
Molecular genomic features associated with in vitro response of the NCI-60 cancer cell line panel to natural products.
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NCI-60癌细胞系对天然产物的体外反应相关的分子基因组特征。
DOI：
10.1002/1878-0261.12849
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发表时间：
2021-03
影响因子：
6.6
通讯作者：
O'Keefe BR
中科院分区：
文献类型：
--
作者：
Krushkal J;Negi S;Yee LM;Evans JR;Grkovic T;Palmisano A;Fang J;Sankaran H;McShane LM;Zhao Y;O'Keefe BR
Natural products provide new opportunities for anticancer chemotherapeutics. We examined the associations of molecular features in the NCI‐60 cancer cell lines with response to 1302 plant, marine, and microbial compounds. Expression or mutations in multiple genes were associated with treatment responses, suggesting potential mechanisms of action of natural compounds. This information will assist in future design of new chemotherapy agents. Natural products remain a significant source of anticancer chemotherapeutics. The search for targeted drugs for cancer treatment includes consideration of natural products, which may provide new opportunities for antitumor cytotoxicity as single agents or in combination therapy. We examined the association of molecular genomic features in the well‐characterized NCI‐60 cancer cell line panel with in vitro response to treatment with 1302 small molecules which included natural products, semisynthetic natural product derivatives, and synthetic compounds based on a natural product pharmacophore from the Developmental Therapeutics Program of the US National Cancer Institute's database. These compounds were obtained from a variety of plant, marine, and microbial species. Molecular information utilized for the analysis included expression measures for 23059 annotated transcripts, lncRNAs, and miRNAs, and data on protein‐changing single nucleotide variants in 211 cancer‐related genes. We found associations of expression of multiple genes including SLFN11, CYP2J2, EPHX1, GPC1, ELF3, and MGMT involved in DNA damage repair, NOTCH family members, ABC and SLC transporters, and both mutations in tyrosine kinases and BRAF V600E with NCI‐60 responses to specific categories of natural products. Hierarchical clustering identified groups of natural products, which correlated with a specific mechanism of action. Specifically, several natural product clusters were associated with SLFN11 gene expression, suggesting that potential action of these compounds may involve DNA damage. The associations between gene expression or genome alterations of functionally relevant genes with the response of cancer cells to natural products provide new information about potential mechanisms of action of these identified clusters of compounds with potentially similar biological effects. This information will assist in future drug discovery and in design of new targeted cancer chemotherapy agents.
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影响因子：
5.1
作者：
Sashidhara, Koneni V.;White, Kimberly N.;Crews, Phillip
通讯作者：
Crews, Phillip
影响因子：
8.4
作者：
Chow MJ;Alfiean M;Pastorin G;Gaiddon C;Ang WH
通讯作者：
Ang WH
影响因子：
2.4
作者：
Dholwani KK;Saluja AK;Gupta AR;Shah DR
通讯作者：
Shah DR
DOI：
10.1007/978-1-4614-0899-4_15
发表时间：
2012-01-01
期刊：
NOTCH SIGNALING IN EMBRYOLOGY AND CANCER
影响因子：
--
作者：
Dang, Thao P.
通讯作者：
Dang, Thao P.
影响因子：
3.8
作者：
Farnedi, Anna;Rossi, Silvia;Perris, Roberto
通讯作者：
Perris, Roberto