Pestana Diogo, Teixeira Diana, Faria Ana, Domingues Valentina, Monteiro Rosário, Calhau Conceição
Department of Biochemistry (U38-FCT), Faculty of Medicine, University of Porto, Centro de Investigação Médica, Rua Dr. Plácido da Costa, Porto, Portugal.
Environ Toxicol. 2015 Feb;30(2):168-76. doi: 10.1002/tox.21882. Epub 2013 Aug 2.
Human exposure to persistent organic pollutants (POPs) is a certainty, even to long banned pesticides like o,p'-dichlorodiphenyltrichloroethane (o,p'-DDT), and its metabolites p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE), and p,p'-dichlorodiphenyldichloroethane (p,p'-DDD). POPs are known to be particularly toxic and have been associated with endocrine-disrupting effects in several mammals, including humans even at very low doses. As environmental estrogens, they could play a critical role in carcinogenesis, such as in breast cancer. With the purpose of evaluating their effect on breast cancer biology, o,p'-DDT, p,p'-DDE, and p,p'-DDD (50-1000 nM) were tested on two human breast adenocarcinoma cell lines: MCF-7 expressing estrogen receptor (ER) α and MDA-MB-231 negative for ERα, regarding cell proliferation and viability in addition to their invasive potential. Cell proliferation and viability were not equally affected by these compounds. In MCF-7 cells, the compounds were able to decrease cell proliferation and viability. On the other hand, no evident response was observed in treated MDA-MB-231 cells. Concerning the invasive potential, the less invasive cell line, MCF-7, had its invasion potential significantly induced, while the more invasive cell line MDA-MB-231, had its invasion potential dramatically reduced in the presence of the tested compounds. Altogether, the results showed that these compounds were able to modulate several cancer-related processes, namely in breast cancer cell lines, and underline the relevance of POP exposure to the risk of cancer development and progression, unraveling distinct pathways of action of these compounds on tumor cell biology.
人类接触持久性有机污染物(POPs)是确定无疑的,即使是接触早已被禁用的农药,如o,p'-二氯二苯三氯乙烷(o,p'-DDT)及其代谢产物p,p'-二氯二苯二氯乙烯(p,p'-DDE)和p,p'-二氯二苯二氯乙烷(p,p'-DDD)。已知POPs具有特别强的毒性,即使在非常低的剂量下,也会对包括人类在内的多种哺乳动物产生内分泌干扰作用。作为环境雌激素,它们可能在致癌过程中发挥关键作用,比如在乳腺癌中。为了评估它们对乳腺癌生物学的影响,研究人员用o,p'-DDT、p,p'-DDE和p,p'-DDD(50 - 1000 nM)对两种人乳腺腺癌细胞系进行了测试:表达雌激素受体(ER)α的MCF - 7细胞系和ERα呈阴性的MDA - MB - 231细胞系,测试内容包括细胞增殖、活力以及侵袭潜能。这些化合物对细胞增殖和活力的影响并不相同。在MCF - 7细胞中,这些化合物能够降低细胞增殖和活力。另一方面,在处理过的MDA - MB - 231细胞中未观察到明显反应。关于侵袭潜能,侵袭性较小的细胞系MCF - 7的侵袭潜能显著增强,而侵袭性较强的细胞系MDA - MB - 231在受试化合物存在的情况下,其侵袭潜能大幅降低。总之,结果表明这些化合物能够调节多种癌症相关过程,即在乳腺癌细胞系中,并且强调了接触POPs与癌症发生和发展风险的相关性,揭示了这些化合物在肿瘤细胞生物学上不同作用途径。