Merli Daniele, Profumo Antonella, Bloise Nora, Risi Giulia, Momentè Stefano, Cucca Lucia, Visai Livia
Department of Chemistry, University of Pavia, Via Taramelli 12, 27100 Pavia, Italy.
Molecular Medicine Department (DMM), Center for Health Technologies (CHT), UdR INSTM, University of Pavia, Viale Taramelli 3/B, 27100 Pavia, Italy.
ACS Omega. 2018 Apr 30;3(4):4631-4640. doi: 10.1021/acsomega.7b02026. Epub 2018 Apr 26.
In this study, we aimed to investigate in vitro whether the synthetized indium maltolate (InMal) and gallium maltolate (GaMal) could exert either a toxic effect toward breast cancer cell line MDA-MB-231 or an agonistic activity with mitoxantrone (MTX) in comparison to fibroblast cell line NIH-3T3. Both GaMal and InMal reduced viability of MDA-MB-231, and at a lesser extent of NIH3-T3, in a dose- and time-dependent mode, the outcome was more effective in comparison to MTX sole exposure. Both GaMal and InMal toxicity was reverted by iron citrate addition on NIH3-T3, not on MDA-MB-231, showing indirectly that gallium and indium's mechanisms of action may include iron targeting. The agonistic activity against MDA-MB-231 survival was shown pretreating with 100 μM InMal for 24 h followed by medium exchange with MTX at 10 ng mL or vice-versa but not with co-incubation of both compounds. In particular, InMal pretreating resulted more protective to MTX subsequent exposure.
在本研究中,我们旨在体外研究合成的苹果酸铟(InMal)和苹果酸镓(GaMal)对乳腺癌细胞系MDA-MB-231是否具有毒性作用,以及与成纤维细胞系NIH-3T3相比,它们与米托蒽醌(MTX)是否具有协同活性。GaMal和InMal均以剂量和时间依赖性方式降低了MDA-MB-231的活力,对NIH3-T3的活力降低程度较小,与单独暴露于MTX相比,结果更有效。在NIH3-T3中添加柠檬酸铁可逆转GaMal和InMal的毒性,但在MDA-MB-231中则不能,这间接表明镓和铟的作用机制可能包括靶向铁。对MDA-MB-231存活的协同活性表现为先用100μM InMal预处理24小时,然后用10 ng/mL的MTX更换培养基,反之亦然,但两种化合物共同孵育则无此效果。特别是,InMal预处理对随后暴露于MTX具有更强的保护作用。