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 lowerthan 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.
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 lowerthan 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.
Authors: Mark J de Keijzer; Daniel J de Klerk; Lianne R de Haan; Robert T van Kooten; Leonardo P Franchi; Lionel M Dias; Tony G Kleijn; Diederick J van Doorn; Michal Heger Journal: Methods Mol Biol Date: 2022
Authors: Chuang Zhao; K P Rakesh; Saira Mumtaz; Balakrishna Moku; Abdullah M Asiri; Hadi M Marwani; H M Manukumar; Hua-Li Qin Journal: RSC Adv Date: 2018-03-06 Impact factor: 4.036