Browsing by Author "Marques, Maria P. M."
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- Lipophilic Caffeic and Ferulic Acid Derivatives Presenting Cytotoxicity against Human Breast Cancer CellsPublication . Serafim, Teresa L.; Carvalho, Filipa S.; Marques, Maria P. M.; Calheiros, Rita; Silva, Tiago; Garrido, J.M.P.J.; Milhazes, Nuno; Borges, Fernanda; Roleira, Fernanda; Silva, Elisário T.; Holy, Jon; Oliveira, Paulo J.In the present work, lipophilic caffeic and ferulic acid derivatives were synthesized, and their cytotoxicity on cultured breast cancer cells was compared. A total of six compounds were initially evaluated: caffeic acid (CA), hexyl caffeate (HC), caffeoylhexylamide (HCA), ferulic acid (FA), hexyl ferulate (HF), and feruloylhexylamide (HFA). Cell proliferation, cell cycle progression, and apoptotic signaling were investigated in three human breast cancer cell lines, including estrogen-sensitive (MCF-7) and insensitive (MDA-MB-231 and HS578T). Furthermore, direct mitochondrial effects of parent and modified compounds were investigated by using isolated liver mitochondria. The results indicated that although the parent compounds presented no cytotoxicity, the new compounds inhibited cell proliferation and induced cell cycle alterations and cell death, with a predominant effect on MCF-7 cells. Interestingly, cell cyle data indicates that effects on nontumor BJ fibroblasts were predominantly cytostatic and not cytotoxic. The parent compounds and derivatives also promoted direct alterations on hepatic mitochondrial bioenergetics, although the most unexpected and never before reported one was that FA induces the mitochondrial permeability transition. The results show that the new caffeic and ferulic acid lipophilic derivatives show increased cytotoxicity toward human breast cancer cell lines, although the magnitude and type of effects appear to be dependent on the cell type. Mitochondrial data had no direct correspondence with effects on intact cells suggesting that this organelle may not be a critical component of the cellular effects observed. The data provide a rational approach to the design of effective cytotoxic lipophilic hydroxycinnamic derivatives that in the future could be profitably applied for chemopreventive and/or chemotherapeutic purposes.
- Preclinical pharmacokinetics and biodistribution of Anticancer Dinuclear Palladium(II)-Spermine Complex (Pd2Spm) in micePublication . Vojtek, Martin; Gonçalves-Monteiro, Salomé; Pinto, Edgar; Kalivodová, Sára; Almeida, Agostinho; Marques, Maria P. M.; Carvalho, Ana L. M. Batista de; Martins, Clara B.; Mota-Filipe, Hélder; Ferreira, Isabel M. P. L. V. O.; Diniz, CarmenPalladium-based compounds are regarded as potential analogs to platinum anticancer drugs with improved properties. The present study assessed the pharmacokinetics and biodistri bution of a dinuclear palladium(II)-spermine chelate (Pd2Spm), which has previously been shown to possess promising in vitro activity against several therapy-resistant cancers. Using inductively coupled plasma-mass spectrometry, the kinetic profiles of palladium/platinum in serum, serum ultrafiltrate and tissues (kidney, liver, brain, heart, lungs, ovaries, adipose tissue and mammary glands) were studied in healthy female Balb/c mice after a single intraperitoneal bolus injection of Pd2Spm (3 mg/kg bw) or cisplatin (3.5 mg/kg bw) between 0.5 and 48 h post-injection. Palladium in serum exhibited biphasic kinetics with a terminal half-life of 20.7 h, while the free palladium in serum ultrafiltrate showed a higher terminal half-life than platinum (35.5 versus 31.5 h). Palladium was distributed throughout most of the tissues except for the brain, with the highest values in the kidney, followed by the liver, lungs, ovaries, adipose tissue and mammary glands. The in vitro cellular accu mulation was also evaluated in breast cancer cells, evidencing a passive diffusion as a mechanism of Pd2Spm’s cellular entry. This study reports, for the first time, the favorable pharmacokinetics and biodistribution of Pd2Spm, which may become a promising pharmacological agent for cancer treatment.
- Preclinical pharmacokinetics and biodistribution of anticancer dinuclear Palladium(II)-Spermine Complex (Pd2Spm) in micePublication . Vojtek, Martin; Gonçalves-Monteiro, Salomé; Pinto, Edgar; Kalivodová, Sára; Almeida, Agostinho; Marques, Maria P. M.; Batista de Carvalho, Ana L. M.; Martins, Clara B.; Mota-Filipe, Helder; Ferreira, Isabel M. P. L. V. O.; Diniz, CarmenPalladium-based compounds are regarded as potential analogs to platinum anticancer drugs with improved properties. The present study assessed the pharmacokinetics and biodistribution of a dinuclear palladium(II)-spermine chelate (Pd2Spm), which has previously been shown to possess promising in vitro activity against several therapy-resistant cancers. Using inductively coupled plasma-mass spectrometry, the kinetic profiles of palladium/platinum in serum, serum ultrafiltrate and tissues (kidney, liver, brain, heart, lungs, ovaries, adipose tissue and mammary glands) were studied in healthy female Balb/c mice after a single intraperitoneal bolus injection of Pd2Spm (3 mg/kg bw) or cisplatin (3.5 mg/kg bw) between 0.5 and 48 h post-injection. Palladium in serum exhibited biphasic kinetics with a terminal half-life of 20.7 h, while the free palladium in serum ultrafiltrate showed a higher terminal half-life than platinum (35.5 versus 31.5 h). Palladium was distributed throughout most of the tissues except for the brain, with the highest values in the kidney, followed by the liver, lungs, ovaries, adipose tissue and mammary glands. The in vitro cellular accumulation was also evaluated in breast cancer cells, evidencing a passive diffusion as a mechanism of Pd2Spm’s cellular entry. This study reports, for the first time, the favorable pharmacokinetics and biodistribution of Pd2Spm, which may become a promising pharmacological agent for cancer treatment