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New derivatives of lupane triterpenoids disturb breast cancer mitochondria and ...

Serafim, Teresa L.; Carvalho, Filipa S.; Bernardo, Telma C.; Pereira, Gonçalo C.; Perkins, Edward; Holy, Jon; Krasutsky, Dmytro A.

Novel cationic dimethylaminopyridine derivatives of pentacyclic triterpenes were previously described to promote mitochondrial depolarization and cell death in breast and melanoma cell lines. The objective of this work was to further investigate in detail the mechanism of mitochondrial perturbations, correlating those effects with breast cancer cell responses to those same agents. Initially, a panel of tumor an...


Mitochondrial apoptosis-inducing factor is involved in doxorubicin-induced toxi...

Moreira, Ana C.; Branco, Ana F.; Sampaio, Susana F.; Cunha-Oliveira, Teresa; Martins, Tatiana R.; Holy, Jon; Oliveira, Paulo J.; Sardão, Vilma A.

The cardiotoxicity induced by the anti-cancer doxorubicin involves increased oxidative stress, disruption of calcium homeostasis and activation of cardiomyocyte death. Nevertheless, antioxidants and caspase inhibitors often show little efficacy in preventing cell death. We hypothesize that a caspase-independent cell death mechanism with the release of the apoptosis-inducing factor from mitochondria is involved ...


Dimethylaminopyridine derivatives of lupane triterpenoids cause mitochondrial d...

Bernardo, Telma C.; Cunha-Oliveira, Teresa; Serafim, Teresa L.; Holy, Jon; Krasutsky, Dmytro; Kolomitsyna, Oksana; Krasutsky, Pavel; Moreno, A. J. M.

Triterpenoids are a large class of naturally occurring compounds, and some potentially interesting as anticancer agents have been found to target mitochondria. The objective of the present work was to investigate the mechanisms of mitochondrial toxicity induced by novel dimethylaminopyridine (DMAP) derivatives of pentacyclic triterpenes, which were previously shown to inhibit the growth of melanoma cells in vit...


Lipophilic Caffeic and Ferulic Acid Derivatives Presenting Cytotoxicity against...

Serafim, Teresa L.; Carvalho, Filipa S.; Marques, Maria P. M.; Calheiros, Rita; Silva, Tiago; Garrido, Jorge; Milhazes, Nuno; Borges, Fernanda

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 wer...


Biologic Activity of a Dinuclear Pd(II)-Spermine Complex Toward Human Breast Ca...

Fiuza, Sónia M.; Holy, Jon; Carvalho, Luís A. E. Batista de; Marques, Maria P. M.

A dinuclear palladium-based complex (Pd(2) -Spm) was synthesized and compared with cisplatin (cDDP) on two different human breast cancer cell lines (MCF-7 and MDA-MB-231) as well as toward an untransformed cell line (BJ fibroblasts). The results obtained show that Pd(2) -Spm is more effective against the estrogen receptors [ER(-)] cell line MDA-MB-231, while cDDP displayed better results for the ER(+) MCF-7 cel...


Lipophilic Caffeic and Ferulic Acid Derivatives Presenting Cytotoxicity against...

Serafim, Teresa L.; Carvalho, Filipa S.; Marques, Maria P. M.; Calheiros, Rita; Silva, Tiago; Garrido, J.M.P.J.; Milhazes, Nuno; Borges, Fernanda

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 wer...


Different concentrations of berberine result in distinct cellular localization ...

Serafim, Teresa; Oliveira, Paulo; Sardão, Vilma; Perkins, Ed; Parke, Donna; Holy, Jon

Abstract Purpose Natural products represent a rich reservoir of potential small molecule inhibitors exhibiting antiproliferative and tumoricidal properties. An example is the isoquinoline alkaloid berberine, which is found in plants such as goldenseal (Hydrastis canadensis). Studies have shown that berberine is able to trigger apoptosis in different malignant cell lines, and can also lead to cell cycle arrest a...


Morphological alterations induced by doxorubicin on H9c2 myoblasts: nuclear, mi...

Sardão, Vilma; Oliveira, Paulo; Holy, Jon; Oliveira, Catarina; Wallace, Kendall

Abstract Doxorubicin (Dox) is a very potent antineoplastic agent used against several types of cancer, despite a cumulative cardiomyopathy that reduces the therapeutic index for treatment. H9c2 myoblast cells have been used as an in vitro model to study biochemical alterations induced by Dox treatment on cardiomyocyte cells. Despite the extensive work already published, few data are available regarding morpholo...


Sanguinarine cytotoxicity on mouse melanoma K1735-M2 cells--Nuclear vs. mitocho...

Serafim, Teresa L.; Matos, Júlio A. C.; Sardão, Vilma A.; Pereira, Gonçalo C.; Branco, Ana F.; Pereira, Sandro L.; Parke, Donna; Perkins, Edward L.

http://www.sciencedirect.com/science/article/B6T4P-4T193YB-5/2/8b89adb1a424a742b294db27ed9982c6


Mitochondrially targeted effects of berberine [Natural Yellow 18, 5,6-dihydro-9...

Pereira, Gonçalo C.; Branco, Ana F.; Matos, Júlio A. C.; Pereira, Sandro L.; Parke, Donna; Perkins, Edward L.; Serafim, Teresa L.; Sardão, Vilma A.

Berberine [Natural Yellow 18, 5,6-dihydro-9,10-dimethoxybenzo(g)-1,3-benzodioxolo(5,6-a)quinolizinium] is an alkaloid present in plant extracts and has a history of use in traditional Chinese and Native American medicine. Because of its ability to arrest the cell cycle and cause apoptosis of several malignant cell lines, it has received attention as a potential anticancer therapeutic agent. Previous studies sug...


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