Balzarini J, Verstuyf A, Hatse S, Goebels J, Sobis H, Vandeputte M, De Clercq E
Laboratory of Virology and Experimental Chemotherapy, Rega Institute for Medical Research, Catholic University, Louvain, Belgium.
Int J Cancer. 1995 Mar 29;61(1):130-7. doi: 10.1002/ijc.2910610122.
9-(2-phosphonylmethoxyethyl)adenine (PMEA) is the prototype compound of a series of acyclic nucleoside phosphonate derivatives endowed with potent and selective anti-retroviral activity in vitro and in vivo. We have now found that PMEA is also a potent inducer of differentiation of a number of tumor cells, including human erythroleukemia K562 cells, rat choriocarcinoma RCHO cells and human acute promyelocytic leukemic HL-60 cells. At 10 microM PMEA, rat RCHO cell cultures could be almost fully differentiated, and at 50 microM PMEA, approximately 50% of the K562 cells could be triggered to produce hemoglobin. The differentiating activity of butyric acid was at least partially additive to that of PMEA when both drugs were combined in K562 cell cultures. PMEA needs to be present for at least 2 or 3 days in the K562 cell cultures to achieve optimal differentiating activity. This suggests that either a PMEA metabolite and/or its anti-metabolic effects may be responsible for differentiation of the tumor cells.
9-(2-膦酰甲氧基乙基)腺嘌呤（PMEA）是一系列无环核苷膦酸酯衍生物的原型化合物，在体外和体内均具有强效且选择性的抗逆转录病毒活性。我们现在发现，PMEA也是多种肿瘤细胞分化的强效诱导剂，包括人红白血病K562细胞、大鼠绒毛膜癌RCHO细胞和人急性早幼粒细胞白血病HL-60细胞。在10微摩尔/升的PMEA作用下，大鼠RCHO细胞培养物几乎可完全分化，在50微摩尔/升的PMEA作用下，约50%的K562细胞可被触发产生血红蛋白。当两种药物在K562细胞培养物中联合使用时，丁酸的分化活性与PMEA的分化活性至少部分具有相加性。在K562细胞培养物中，PMEA需要存在至少2或3天才能达到最佳分化活性。这表明，可能是PMEA的代谢产物和/或其抗代谢作用导致了肿瘤细胞的分化。
