Anticancer activity of some polyamine derivatives on human prostate and breast cancer cell lines

Abstract

The aim of this study was to expand our knowledge about anticancer activity of some polyamine derivatives with quinoline or chromane as terminal moieties. Tested compounds were evaluated in vitro towards metastatic human prostate adenocarcinoma (PC3), human carcinoma (DU145) and mammary gland adenocarcinoma (MCF7) cell lines. Cell viability was estimated on the basis of mitochondrial metabolic activity using water-soluble tetrazolium WST1 to establish effective concentrations of the tested compounds under experimental conditions. Cytotoxic potential of polyamine derivatives was determined by the measurement of lactate dehydrogenase activity released from damaged cells, changes in mitochondrial membrane potential, the cell cycle distribution analysis and apoptosis assay. It was revealed that the tested polyamine derivatives differed markedly in their antiproliferative activity. Bischromane derivative 5a exhibited a rather cytostatic than cytotoxic effect on the tested cells, whereas quinoline derivative 3a caused changes in cell membrane integrity, inhibited cell cycle progression, as well as induced apoptosis of prostate and breast cancer cells which suggest its potential application in cancer therapy.

DNA Interaction Studies of Selected Polyamine Conjugates

“…IC 50 values for the most active derivative 2a were in the range of 16.8 to 26.6 µM depending on cancer cell line. In addition, 2a induced programed cell death in prostate and breast cancer cell lines by an intrinsic pathway, which involved depolarization of mitochondria together with disruption of its membrane [ 31 , 32 , 33 ]. The design of effective anticancer drugs requires not only the biological activity assessment but also an understanding of the mechanisms involved in the process of eliminating cancer cells.…”

“…In addition, 2a induced programed cell death in prostate and breast cancer cell lines by intrinsic pathway, which involved depolarization of mitochondria together with disruption of its membrane [ 31 , 32 , 33 ]. Our studies revealed that anticancer effectiveness of this group of compounds strongly depends on cancer cell line type [ 31 , 32 , 33 ] but these differences may also have their origin in the way the compounds bind to double helix. Therefore, expanding our knowledge about the possible interaction of these compounds with dsDNA or its associated targets such as topoisomerases is of equal importance.…”

“…Based on previous data, it can be postulated that the biological activity of polyamine derivatives with bicyclic chromophores depends on the differences in their spatial structure [ 31 , 32 , 33 ]. Due to the fact that these compounds have been designed as potential intercalators, further studies are focused on the explanation of the influence of both molecule subunits, namely terminal aromatic rings, and the linker on the dsDNA binding properties.…”

Design, Synthesis, and Dual Evaluation of Quinoline and Quinolinium Iodide Salt Derivatives as Potential Anticancer and Antibacterial Agents

“…Quinoline compounds can induce and regulate some transcription factors to mediate apoptosis and metabolism, and inhibit the occurrence of cancer and tumors. In addition, quinoline compounds have been confirmed in related studies, which can be effective in inhibiting the development and progression of cancer and tumors …”

“…In addition, quinoline compounds have been confirmed in related studies, which can be effective in inhibiting the development and progression of cancer and tumors. [17][18][19][20][21] On the other hand, infectious diseases recently have faced major challenges in the world. The number of people with various plagues and deaths has increased considerably.…”