Guaiazulene: biochemical activity and cytotoxic and genotoxic effects on rat neuron and N2a neuroblastom cells

Abstract

Aim:Neuroblastoma (NB)cells are often used in cancer researches such as glioblastoma cells since they have the potential of high mitotic activity, nuclear pleomorphism, and tumor necrosis. Guaiazulene (GYZ 1,4-dimethyl-7-isopropylazulene)is present in several essential oils of medicinal and aromatic plants. Many studies have reported the cytotoxic effect of GYZ; however, there are no studies that compare such effects between cancer cell lines and normal human cells after treatment with GYZ.Materials and Methods:In this study, we aimed to describe in vitro antiproliferative and/or cytotoxic properties (by 3-[4,5 dimetylthiazol -2-yl]-2,5 diphenlytetrazolium bromide [MTT] test), oxidative effects (by total antioxidant capacity [TAC] and total oxidative stress [TOS] analysis)and genotoxic damage potentials (by single cell gel electrophoresis)of GYZ.Result:The results indicated that GYZ have anti-proliferative activity suppressing the proliferation of neuron and N2a-NB cells at high doses. In addition, GYZ treatments at higher doses led to decreases of TAC levels and increases of TOS levels in neuron and N2a-NB cells. On the other hand, the mean values of the total scores of cells showing DNA damage were not found different from the control values.Conclusion:From this study, it is observed that GYZ has in vitro cytotoxic activity against neuron and N2a-NB cells.

Quantitative Structure–Cytotoxicity Relationship of Azulene Amide Derivatives

“…These data suggest that the antitumor-potential of guaiazulenes can be estimated by their molecular shape and hydrophobicity. By closer inspection, [9] (100~400 μM) and [17] (13~100 μM) were found to stimulate the growth of normal oral cells. The biological significance of this hormetic growth stimulation (28) remains to be investigated.…”

“…showed higher TS and PSE values, than [1][2][3][4][5][6][7] and [15][16][17][18][19][20][21]. The most active compound [8][9][10][11][12][13][14] induced apoptosis in C9-22 OSCC cells at 4-times higher CC 50 . Quantitative structure-activity relationship analysis of [1][2][3][4][5][6][7][8][9][10][11][12][13][14] demonstrated that their tumorspecificity was correlated with chemical descriptors that explain the molecular shape and hydrophobicity.…”

“…The most active compound [8][9][10][11][12][13][14] induced apoptosis in C9-22 OSCC cells at 4-times higher CC 50 . Quantitative structure-activity relationship analysis of [1][2][3][4][5][6][7][8][9][10][11][12][13][14] demonstrated that their tumorspecificity was correlated with chemical descriptors that explain the molecular shape and hydrophobicity. Conclusion: 7-Isopropyl-3-methyl-N-propylazulene-1-carboxamide [8] can be a potential candidate of lead compound for manufacturing new anticancer drug.…”

“…Guaiazulene also inhibited CYP1A2 that participates in the formation of toxic metabolite N-acetyl-pbenzoquinone imine (NAPQI) and the metabolic activation of several toxic and carcinogenic compounds (6). On the other hand, there is a limited number of studies that have investigated the cytotoxicity of guaiazulene against human malignant (7)(8)(9) and non-malignant cells (9,10).…”

“…Computational analysis. Since 3-methyl-N-alkylazulene-1carboxamides [1-7] (Group A), 7-Isopropyl-3-methyl-Nalkylazulene-1-carboxamides[8][9][10][11][12][13][14] (Group B) showed a higher tumor-specificity than 2-methoxy-N-alkylazulene-1carboxamides[15-21] (Group C), QSAR analysis was Imanari et al: QSAR of Azulene Amide Derivatives 3513 Determination of coefficient between chemical descriptors and cytotoxicity of 14 Group A and B compounds against tumor cells (defined as T). The mean (pCC 50 i.e., the −log CC 50 ) values for tumor cell lines were defined as T.performed with Group A and B compounds [1-14].…”