Abstract
Sodium pancratistatin 3,4- O-cyclic phosphate ( 2) is a novel water-soluble synthetic derivative of pancratistatin ( 1), a natural alkaloid constituent of Amaryllidaceae plants, that exhibits good cytostatic and antineoplastic activity but is highly insoluble. Unlike most other natural alkaloids it does not act by binding to tubulin, and its mechanism of action has yet to be fully elucidated. Here the efficacy of 2 in a human colon adenocarcinoma model, DLD-1, and some understanding of its mode of action are investigated. Agreeing with previous studies, low cytotoxicity in vitro was seen for 2 with IC 50's of 253 and 19.7 microM for 1 and 96 h exposures, respectively. However in vivo the compound caused statistically significant tumor growth delays ( p < 0.01) at its maximum tolerated dose, and significant vascular shutdown and tumor necrosis were observed. Like 1, the compound appeared to have an unconventional mechanism of action with no effect on microtubule structure, yet causing a G 2/M block, while it was seen to disrupt mitochondrial function. The mechanism of action of 1 and 2 appears to be similar. Thus compound 2, being considerably more soluble than 1, has good potential as an anticancer agent, and further investigation is warranted.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
