A novel podophyllotoxin-derived compound GL331 is more potent than its congener VP-16 in killing refractory cancer cells
A novel podophyllotoxin-derived compound GL331 is more potent than its congener VP-16 in killing refractory cancer cells
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DOI：
10.1023/a:1018971313256
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发表时间：
1999-07-01
影响因子：
3.7
通讯作者：
Whang-Peng, J
中科院分区：
文献类型：
--
作者：
Huang, TS;Lee, CC;Whang-Peng, J
目的. GL 331是VP-16的新同系物，并且在体外和体内淋巴瘤系统中均显示出更有效的抗癌活性。为了广泛地探索GL 331的临床价值，我们进一步评估了GL 331在几种来自通常不使用VP-16治疗的癌症的人细胞系中的细胞毒性和诱导凋亡活性。通过MTT和克隆形成存活测定，在多种细胞系中评价了GL 331和VP-16的细胞毒性，包括鼻咽癌、肝细胞癌、胃癌、结肠癌、宫颈癌和神经母细胞瘤癌类型。Western blot分析检测MDR-1在这些细胞系中的表达。采用Annexin V染色流式细胞仪和DNA梯状条带检测法，对GL 331和VP-16的细胞凋亡诱导活性进行评价。GL 331在杀死癌细胞方面显示出比其同类物VP-16更高的效力。GL 331的估计ID 50比VP-16低2.5 - 17倍。GL 331对MDR-1过表达的肝癌细胞株HCC 36和SW 620的杀伤活性也更强。其较高的细胞毒性可能归因于其诱导细胞凋亡的能力的提高。GL 331的压倒性耐药性和较高的癌细胞杀伤活性表明其在临床癌症治疗中的优越性。
Purpose. GL331 is a new homolog of VP-16, and has demonstrated more efficacious anti-cancer activity in both the in vitro and in vivo lymphoma systems. To extensively explore GL331's clinical value, we furthermore evaluate the cytotoxicity and apoptosis-inducing activity of GL331 in several human cell lines from cancers that are not normally treated with VP-16.Methods. By MTT and clonogenic survival assays, the cytotoxicities of GL331 and VP-16 were evaluated in a variety of cell lines including nasopharyngeal, hepatocellular, gastric, colon, cervical, and neuroblastoma cancer types. Western blot analysis was performed to detect the MDR-1 level in these cell lines. By Annexin V-staining flow cytometry and detection of DNA ladders, the apoptosis-inducing activities of GL331 and VP-16 were also evaluated.Results. GL331 showed more efficacy than its congener VP-16 in killing cancer cells. The estimated ID50 of GL331 were 2.5 to 17-fold lower than those of VP-16. GL331 possessed more cell-killing activity even in MDR-1-overexpressing cell lines such as HCC36 and SW620. Its higher cytotoxicity could be attributed by the elevated ability to induce apoptotic cell death.Conclusion. GL331's overriding drug resistance and higher cancer cell-killing activity suggest its superiority in clinical cancer therapy.