Abdel-Latif Mustafa, Riad Ahmed, Soliman Raghda A, Elkhouly Aisha M, Nafae Heba, Gad Mohamed Z, Motaal Amira Abdel, Youness Rana A
Molecular Genetics Research Team (MGRT), Biotechnology Program, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo, Egypt.
Molecular Genetics Research Team (MGRT), Pharmaceutical Biology Department, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo, Egypt.
Mol Cell Biochem. 2022 Apr;477(4):1281-1293. doi: 10.1007/s11010-022-04378-4. Epub 2022 Feb 7.
Triple-Negative Breast Cancer (TNBC) is one of the most aggressive and hot BC subtypes. Our research group has recently shed the light on the utility of natural compounds as effective immunotherapeutic agents. The aim of this study is to investigate the role of a methoxylated quercetin glycoside (MQG) isolated from Cleome droserifolia in harnessing TNBC progression and tuning the tumor microenvironment and natural killer cells cytotoxicity. Results showed that MQG showed the highest potency (IC = 12 µM) in repressing cellular proliferation, colony-forming ability, migration, and invasion capacities. Mechanistically, MQG was found to modulate a circuit of competing endogenous RNAs where it was found to reduce the oncogenic MALAT-1 lncRNA and induce TP53 and its downstream miRNAs; miR-155 and miR-146a. Accordingly, this leads to alteration in several downstream signaling pathways such as nitric oxide synthesizing machinery, natural killer cells' cytotoxicity through inducing the expression of its activating ligands such as MICA/B, ULBP2, CD155, and ICAM-1 and trimming of the immune-suppressive cytokines such as TNF-α and IL-10. In conclusion, this study shows that MQG act as a compelling anti-cancer agent repressing TNBC hallmarks, activating immune cell recognition, and alleviating the immune-suppressive tumor microenvironment experienced by TNBC patients.
三阴性乳腺癌（TNBC）是侵袭性最强且备受关注的乳腺癌亚型之一。我们的研究团队最近揭示了天然化合物作为有效免疫治疗药物的效用。本研究的目的是探讨从丝叶白花菜中分离出的一种甲氧基化槲皮素糖苷（MQG）在抑制TNBC进展、调节肿瘤微环境以及自然杀伤细胞细胞毒性方面的作用。结果表明，MQG在抑制细胞增殖、集落形成能力、迁移和侵袭能力方面表现出最高效力（IC = 12 μM）。从机制上讲，发现MQG可调节竞争性内源性RNA回路，其中它能降低致癌性MALAT-1长链非编码RNA并诱导TP53及其下游miRNA；miR-155和miR-146a。因此，这会导致多种下游信号通路发生改变，如一氧化氮合成机制、通过诱导其激活配体如MICA/B、ULBP2、CD155和ICAM-1的表达来增强自然杀伤细胞的细胞毒性，以及减少免疫抑制细胞因子如TNF-α和IL-10。总之，本研究表明MQG作为一种引人注目的抗癌药物，可抑制TNBC特征，激活免疫细胞识别，并缓解TNBC患者所经历的免疫抑制肿瘤微环境。
