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揭示单胺氧化酶A（MAO-A）抑制在结直肠癌中的复杂性：计算系统生物学、表达模式及抗癌治疗潜力

Unveiling the Intricacies of Monoamine Oxidase-A (MAO-A) Inhibition in Colorectal Cancer: Computational Systems Biology, Expression Patterns, and the Anticancer Therapeutic Potential.

作者信息

Bardaweel Sanaa K, Al-Salamat Husam, Hajjo Rima, Sabbah Dima, Almutairi Shriefa

机构信息

Department of Pharmaceutical Sciences, School of Pharmacy, The University of Jordan, Amman - 11942, Jordan.

Department of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, P.O. Box 130, Amman - 11733, Jordan.

出版信息

ACS Omega. 2024 Aug 9;9(33):35703-35717. doi: 10.1021/acsomega.4c04100. eCollection 2024 Aug 20.

DOI:10.1021/acsomega.4c04100
PMID:39184489
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11339988/
Abstract

Colorectal cancer (CRC) remains a significant health burden globally, necessitating a deeper understanding of its molecular intricacies for effective therapeutic interventions. Elevated monoamine oxidase-A (MAO-A) expression has been consistently observed in CRC tissues, correlating with advanced disease stages and a poorer prognosis. This research explores the systems biology effects of MAO-A inhibition with small molecule inhibitor clorgyline regarding CRC. The applied systems biology approach starts with a chemocentric informatics approach to derive high-confidence hypotheses regarding the antiproliferative effects of MAO-A inhibitors and ends with experimental validation. Our computational results emphasized the anticancer effects of MAO-A inhibition and the chemogenomics similarities between clorgyline and structurally diverse groups of apoptosis inducers in addition to highlighting apoptotic, DNA-damage, and microRNAs in cancer pathways. Experimental validation results revealed that MAO inhibition results in antiproliferative antimigratory activities in addition to synergistic effects with doxorubicin. Moreover, the results demonstrated a putative role of MAO-A inhibition in commencing CRC cellular death by potentially mediating the induction of apoptosis.

摘要

结直肠癌（CRC）在全球范围内仍是一项重大的健康负担，因此有必要更深入地了解其分子复杂性，以便进行有效的治疗干预。在结直肠癌组织中一直观察到单胺氧化酶A（MAO-A）表达升高，这与疾病晚期和较差的预后相关。本研究探讨了小分子抑制剂氯吉兰抑制MAO-A对结直肠癌的系统生物学效应。所应用的系统生物学方法始于以化学为中心的信息学方法，以得出关于MAO-A抑制剂抗增殖作用的高可信度假设，并以实验验证结束。我们的计算结果强调了MAO-A抑制的抗癌作用以及氯吉兰与结构多样的凋亡诱导剂组之间的化学基因组学相似性，此外还突出了癌症通路中的凋亡、DNA损伤和微小RNA。实验验证结果表明，MAO抑制除了与多柔比星具有协同作用外，还具有抗增殖和抗迁移活性。此外，结果证明MAO-A抑制可能通过介导细胞凋亡的诱导在启动结直肠癌的细胞死亡中发挥推定作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab7a/11339988/46d4f128da4b/ao4c04100_0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab7a/11339988/0295781f0bdd/ao4c04100_0001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab7a/11339988/942134e35833/ao4c04100_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab7a/11339988/61ffdcb4bea3/ao4c04100_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab7a/11339988/46d4f128da4b/ao4c04100_0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab7a/11339988/0295781f0bdd/ao4c04100_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab7a/11339988/996d717a4bce/ao4c04100_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab7a/11339988/f99e64cdf053/ao4c04100_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab7a/11339988/942134e35833/ao4c04100_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab7a/11339988/61ffdcb4bea3/ao4c04100_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab7a/11339988/46d4f128da4b/ao4c04100_0006.jpg

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