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AM-18002，一种天然 anmindenol A 的衍生物，增强了小鼠乳腺癌细胞的放射敏感性。

AM-18002, a derivative of natural anmindenol A, enhances radiosensitivity in mouse breast cancer cells.

机构信息

Research Center, Dongnam Institute of Radiological & Medical Sciences, Busan, Republic of Korea.

College of Pharmacy, Pusan National University, Busan, Republic of Korea.

出版信息

PLoS One. 2024 Apr 16;19(4):e0296989. doi: 10.1371/journal.pone.0296989. eCollection 2024.

DOI:10.1371/journal.pone.0296989
PMID:38625901
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11020960/
Abstract

Natural anmindenol A isolated from the marine-derived bacteria Streptomyces sp. caused potent inhibition of inducible nitric oxide synthase without any significant cytotoxicity. This compound consists of a structurally unique 3,10-dialkylbenzofulvene skeleton. We previously synthesized and screened the novel derivatives of anmindenol A and identified AM-18002, an anmindenol A derivative, as a promising anticancer agent. The combination of AM-18002 and ionizing radiation (IR) improved anticancer effects, which were exerted by promoting apoptosis and inhibiting the proliferation of FM3A mouse breast cancer cells. AM-18002 increased the production of reactive oxygen species (ROS) and was more effective in inducing DNA damage. AM-18002 treatment was found to inhibit the expansion of myeloid-derived suppressor cells (MDSC), cancer cell migration and invasion, and STAT3 phosphorylation. The AM-18002 and IR combination synergistically induced cancer cell death, and AM-18002 acted as a potent anticancer agent by increasing ROS generation and blocking MDSC-mediated STAT3 activation in breast cancer cells.

摘要

从海洋来源的链霉菌属细菌中分离得到的天然 anmindenol A 强烈抑制诱导型一氧化氮合酶而无明显细胞毒性。该化合物由结构独特的 3,10-二烷基苯并呋咱骨架组成。我们之前合成并筛选了 anmindenol A 的新型衍生物，发现 anmindenol A 衍生物 AM-18002 是一种很有前途的抗癌剂。AM-18002 与电离辐射 (IR) 的联合使用提高了抗癌效果，其通过促进细胞凋亡和抑制 FM3A 小鼠乳腺癌细胞增殖来发挥作用。AM-18002 增加了活性氧 (ROS) 的产生，并且在诱导 DNA 损伤方面更有效。发现 AM-18002 处理可抑制髓系来源的抑制细胞 (MDSC)、癌细胞迁移和侵袭以及 STAT3 磷酸化的扩增。AM-18002 和 IR 联合协同诱导癌细胞死亡，并且 AM-18002 通过增加 ROS 的产生和阻断 MDSC 介导的 STAT3 在乳腺癌细胞中的激活来发挥强效抗癌作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f69/11020960/44bf2fdfa89e/pone.0296989.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f69/11020960/c3df5727acde/pone.0296989.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f69/11020960/7030776a3da3/pone.0296989.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f69/11020960/78cfc3a9870d/pone.0296989.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f69/11020960/23f1e705086d/pone.0296989.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f69/11020960/44bf2fdfa89e/pone.0296989.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f69/11020960/c3df5727acde/pone.0296989.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f69/11020960/7030776a3da3/pone.0296989.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f69/11020960/78cfc3a9870d/pone.0296989.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f69/11020960/23f1e705086d/pone.0296989.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f69/11020960/44bf2fdfa89e/pone.0296989.g005.jpg

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