Faculty Medical and Life Sciences, Campus Villingen-Schwenningen, Hochschule Furtwangen University, 78120 Furtwangen, Germany.
Department of Hematology, Oncology and Clinical Immunology, University Hospital Düsseldorf, 40225 Düsseldorf, Germany.
Mar Drugs. 2019 Sep 5;17(9):521. doi: 10.3390/md17090521.
There is a variety of antineoplastic drugs that are based on natural compounds from ecological niches with high evolutionary pressure. We used two cell lines (Jurkat J16 and Ramos) in a screening to assess 300 different naturally occurring compounds with regard to their antineoplastic activity. The results of the compounds 4,6-dibromo-2-(2',4'-dibromophenoxy)phenol (P01F03), 4,5,6-tribromo-2-(2',4'-dibromophenoxy)phenol (P01F08), and 5-epi-nakijinone Q (P03F03) prompted us to perform further research. Using viability and apoptosis assays on the cell lines of primary human leukemic and normal hematopoietic cells, we found that P01F08 induced apoptosis in the cell lines at IC50 values between 1.61 and 2.95 μM after 72 h. IC50 values of peripheral blood mononuclear cells (PBMNCs) from healthy donors were higher, demonstrating that the cytotoxicity in the cell lines reached 50%, while normal PBMNCs were hardly affected. The colony-forming unit assay showed that the hematopoietic progenitor cells were not significantly affected in their growth by P01F08 at a concentration of 3 μM. P01F08 showed a 3.2-fold lower IC50 value in primary leukemic cells [acute myeloid leukemia (AML)] compared to the PBMNC of healthy donors. We could confirm the antineoplastic effect of 5-epi-nakijinone Q (P03F03) on the cell lines via the induction of apoptosis but noted a similarly strong cytotoxic effect on normal PBMNCs.
有各种各样的抗肿瘤药物，它们基于具有高进化压力的生态位的天然化合物。我们使用两种细胞系（Jurkat J16 和 Ramos）进行筛选，以评估 300 种不同的天然存在的化合物的抗肿瘤活性。化合物 4,6-二溴-2-(2',4'-二溴苯氧基)苯酚（P01F03）、4,5,6-三溴-2-(2',4'-二溴苯氧基)苯酚（P01F08）和 5-表-纳曲酮 Q（P03F03）的结果促使我们进行了进一步的研究。我们在原代人类白血病和正常造血细胞的细胞系上进行了细胞活力和凋亡测定，发现 P01F08 在 72 小时后在细胞系中的 IC50 值为 1.61-2.95 μM 时诱导凋亡。来自健康供体的外周血单个核细胞（PBMNC）的 IC50 值更高，表明细胞系中的细胞毒性达到 50%，而正常 PBMNC 几乎不受影响。集落形成单位测定表明，造血祖细胞在 3 μM 浓度的 P01F08 作用下其生长未受到明显影响。与健康供体的 PBMNC 相比，P01F08 在原代白血病细胞（急性髓细胞白血病（AML））中的 IC50 值低 3.2 倍。我们可以通过诱导凋亡来证实 5-表-纳曲酮 Q（P03F03）对细胞系的抗肿瘤作用，但也注意到它对正常 PBMNC 具有类似的强细胞毒性作用。
