Possibility of a new synthetics from lamellarins: anti-leukemic and integrase-inhibitory effects against HTLV-1-related leukemia cells.

片螺素是一类从海洋无脊椎动物中分离得到的六环吡咯生物碱，具有良好的抗肿瘤活性。还报道了片螺素α 20-硫酸盐抑制HIV-1整合酶。在本研究中，我们研究了抗肿瘤活性对HTLV-1相关的白血病细胞系和活性的整合酶抑制HTLV-1通过使用新合成的片螺素。我们重点研究了一种新的片螺素合成物5号，它对HTLV-1相关的白血病细胞系和ATL细胞显示出有效的抗肿瘤活性，但对健康供体的PBMC没有伤害。基因芯片分析表明，5号制剂上调了独特的烟草中毒相关基因。我们仍在继续研究凋亡途径的机制以及由一种新的片螺素合成物引起的整合酶抑制作用。

Lamellarins, a family of hexacyclic pyrrole alkaloids originally isolated from marine invertebrates, has promising anti-tumor activity. It is also reported that lamellarin alpha 20-sulfate inhibits HIV-1 integrase. In the present study, we investigated anti-tumor activity against HTLV-1 related leukemia cell lines and activity of integrase inhibition of HTLV-1 by using new synthesis of lamellarins. We focused on an agent No.5, a new synthetics from lamellarins, that showed potent anti-tumor activity against HTLV-1 related leukemia cell lines and ATL cells but no harm to PBMCs from healthy donors. Microarray analysis indicated that unique apoptosis-related genes were up-regulated by the No.5 agent. We still continue investigating the mechanisms of apoptotic pathways as well as function of integrase inhibition caused by a new synthetics from lamellarins.