Abstract
The development of transition-metal-based antitumor drug candidates increases the metallopharmaceuticals study dramatically. Two trans-thiosemicarbazone-based, Schiff base palladium (Pd) (II) complexes, DMABTSPd (TSPd) and DMABPTSPd (PTSPd), were prepared and characterized as described in our previous study. Here, we investigated whether the two complexes have antitumor effect on human gastric adenocarcinoma cell lines, BGC-823 and SGC-7901, compared with normal human gastric mucosal epithelial cell line, Ges-1. The results show that the Pd complex with the bare amino group (DMABTSPd(TSPd)) can inhibit cell viabilities and induce apoptosis in human gastric carcinoma cells, rather than the Pd complex without the bare amino group (DMABPTSPd (PTSPd)). This occurs via a mitochondrial-related pathway by down-regulating the level of Bcl-2 expression and up-regulating the level of Bid expression. Meanwhile, DMABTSPd (TSPd) suppressed tumor growth via a mitochondrial-related pathway in a nude mouse tumor xenograft model derived from BGC-823 cells. These findings demonstrate that DMABTSPd (TSPd) is worthy of further structural optimization and representing a promising Pd complex for the development of a new antitumor therapeutic agent.
Highlights
The discovery of the antitumor activity of transitionmetal-based drug candidates causes research into metallopharmaceuticals to increase dramatically [1,2,3,4]
The results show that the Pd complex with the bare amino group (DMABTSPd(TSPd)) can inhibit cell viabilities and induce apoptosis in human gastric carcinoma cells, rather than the Pd complex without the bare amino group (DMABPTSPd (PTSPd))
We investigated the antitumor activity and mechanism of two trans-thiosemicarbazone, Schiff base palladium (Pd) complexes DMABTSPd(TSPd), with bare amino group, and DMABPTSPd (PTSPd), without bare amino group (Figure 1A and 1B ) in human gastric adenocarcinoma cell lines, BGC-823 and SGC-7901, in vitro and in vivo, compared to normal human gastric mucosal epithelial cell line, Ges-1.In our target complexes, the thiosemicarbazone-based Schiff base Pd (II) complexes, the ligands are bonded to the Pd (II) center with an N, S-bidentate coordination mode
Summary
The discovery of the antitumor activity of transitionmetal-based drug candidates (such as Pt, Pd, and Mo complexes) causes research into metallopharmaceuticals to increase dramatically [1,2,3,4] These metal complexes have good activity towards one or more tumor cell lines, and some have entered clinical trials. The major problems with transition-metal-based antitumor drugs are their side effects and cell resistance, varying from nephrotoxicity to drug resistance of the tumor cells, along with limited applicability towards certain cancer cell lines [5, 6].
Sign-in/Register to view highlights & summary 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.
