Abstract
Cytotoxic effects of the Annonaceous acetogenin, bullatacin, were studied in multidrug-resistant (MDR) human mammary adenocarcinoma (MCF-7/Adr) cells vs. the parental non-resistant wild type (MCF-7/wt) cells. Bullatacin was effectively cytotoxic to the MCF-7/Adr cells while it was more cytostatic to the MCF-7/wt cells. ATP depletion is the mode of action of the Annonaceous acetogenins, and these agents offer a special advantage in the chemotherapeutic treatment of MDR tumors that have ATP-dependent mechanisms.
Highlights
In many cancer patients, the eventual cause of death is not from the original, chemotherapeutically responsive, tumor cells but from the surviving tumor cells that develop resistance to both the original antineoplastic agent and to new, mechanistically and structurally unrelated compounds [1,2]
A second, related, mode of action is the inhibition of an ubiquinone-linked NADH oxidase, involved in substrate level phosphorylation, which is constitutively expressed in the plasma membranes of cancer cells and only transiently expressed in the membranes of 'normal' noncancerous cells [15]
Bullatacin was found to be cytotoxic to the multidrug resistance (MDR) MCF-7/Adr cells, but it was only cytostatic to the MCF-7/wt cells
Summary
The eventual cause of death is not from the original, chemotherapeutically responsive, tumor cells but from the surviving tumor cells that develop resistance to both the original antineoplastic agent and to new, mechanistically and structurally unrelated compounds [1,2]. This phenomena has been accurately coined multidrug resistance (MDR) and is often characterized by the increased expression of a 170 kDa phospholipid glycoprotein (P-gp). Bullatacin was found to be cytotoxic to the MDR MCF-7/Adr cells, but it was only cytostatic to the MCF-7/wt cells
Sign-in/Register to view highlights & summary 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.
