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COMBINATIONS OF ISOTHIOCYANATES WITH DRUGS – A CHANCE OR THREAT TO CHEMOPREVENTION AND CANCER TREATMENT?

100%

Mielczarek L., Chilmonczyk Z., Suchocki P., Wroczyński P., Wiktorska K.

Acta Poloniae Pharmaceutica - Drug Research

2018

vol. 75

issue 4

829-841

Isothiocyanates (ITCs) are a group of compounds of natural origin which exhibit anticancer properties. In addition to the cytotoxic impact on cancer cells, confirmed in the multiple cell lines and the in vivo models, ITCs exhibit the cytoprotective effect in normal cells by regulating the activity of enzymes involved in xenobiotic metabolism. These properties of ITCs have led to a continuing increase in the number of studies which have shown that ITCs can sensitize cancer cells to cytostatic drugs used as standard in cancer therapies. On the other hand these compounds may decrease the effectiveness of drugs by deregulating the metabolising system of the cell. This paper discusses the results of preclinical study on ITCs applications in combination therapy as well as their role in drug metabolism.

Cytotoxicity of PP(Arg)2- and Hp(Arg)2-mediated photodynamic therapy and early stage of apoptosis induction in prostate carcinoma in vitro

100%

Nowak-Stępniowska A., Wiktorska K., Małecki M., Romiszewska A., Padzik-Graczyk A.

Porphyrin photosensitizers tend to localize in mitochondria. The depolarization of mitochondrial membrane is one of the early stages of apoptosis and Laser Scanning Fluorescence Microscopy allows to determine changes in transmembrane mitochondrial potential under influence of PDT depending on the kind of photosensitizer (PP(Arg)2, Hp(Arg)2), the energy dose (5, 10, 30 and 50 J/cm2) and time periods (24 and 48 hours after irradiation) in the LNCaP (lymphonodal metastasis of prostate carcinoma, the androgen dependent cell line). Cyototoxicity induced by PP(Arg)2- and Hp(Arg)2-based PDT depending on energy dose and time after irradiation in prostate carcinoma is determined with MTT. Generally, it was shown that lower energy doses induce greater changes in transmembrane mitochondrial potential. Hp(Arg)2-based PDT was more effective causing greater mitochondrial membrane depolarization and cell viability decrease in comparison to PP(Arg)2-mediated PDT (in the case of maximal nontoxic photosensitizer doses used).

Cytotoxicity of PP(Arg)2- and PP(Ala)2(Arg)2-based photodynamic therapy and early stage of apoptosis induction in human breast cancers in vitro

86%

Nowak-Stępniowska A., Wiktorska K., Małecki M., Milczarek M., Lubelska K., Padzik-Graczyk A.

2012

vol. 59

issue 4

603-611

Mitochondria are cell energetic centers where ATP is produced. They also play a very important role in the PDT as intracellular sites of photosensitizer localization. Photosensitizers gathering in mitochondria (like porphyrin derivatives used in this work) are more effective in tumor cell destruction. Moreover, it was assumed that di-amino acid substituents attached to porphyrin ring will strengthen the effectivity of interaction with membrane receptors of examined cells. MTT assay was performed to investigate the influence of PP(Arg)2 and PP(Ala)2(Arg)2-based PDT on breast cancer cell viability for 24 h, 48 h and 120 h after cell irradiation. Then the influence of PP(Ala)2(Arg)2- and PP(Arg)2-mediated PDT on early mitochondrial apoptosis induction via measurements of the transmembrane mitochondrial potential changes was examined. Results showed that lower energy doses and maximal nontoxic photosensitizer doses of PP(Ala)2(Arg)2 and PP(Arg)2 applied in PDT can imply apoptotic cell death. It was confirmed that modification of the protoporphyrin IX by attaching two alanine substituents raised the efficiency of photodynamic therapy.

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2 Acta Biochimica Polonica

1 Acta Poloniae Pharmaceutica - Drug Research

1 2018

1 2012

1 2011

3 Wiktorska K.

2 Małecki M.

2 Nowak-Stępniowska A.

2 Padzik-Graczyk A.

1 Chilmonczyk Z.

1 Lubelska K.

1 Mielczarek L.

1 Milczarek M.

1 Romiszewska A.

1 Suchocki P.

1 Wroczyński P.

Search results

COMBINATIONS OF ISOTHIOCYANATES WITH DRUGS – A CHANCE OR THREAT TO CHEMOPREVENTION AND CANCER TREATMENT?

Cytotoxicity of PP(Arg)2- and Hp(Arg)2-mediated photodynamic therapy and early stage of apoptosis induction in prostate carcinoma in vitro

Cytotoxicity of PP(Arg)2- and PP(Ala)2(Arg)2-based photodynamic therapy and early stage of apoptosis induction in human breast cancers in vitro