In an effort to study curcumin analogues as an alternative to improve the therapeutic efficacy of curcumin, we screened the cytotoxic potential of four diarylpentanoids using the HeLa and CaSki cervical cancer cell lines. merits further investigation into its chemotherapeutic role for cervical cancer. cervical cancer research, and contain the high risk HPV types 18 and 16 viral genomes respectively. As seven out of ten cases of invasive cervical cancers are due to infection by these high risk subtypes, the use of these cell lines in the study is relevant [2] particularly. Furthermore, as HPV oncogenes play an essential role within the development of cervical tumor, the analysis was extended to add the study from the potential role from the chosen diarylpentanoid in inhibiting the manifestation of E6 and E7 oncogenes in HPV16 and HPV18-contaminated cervical tumor cells. The purpose of this scholarly research was to look for the cytotoxic, anti-proliferative and apoptotic activity of chosen diarylpentanoid treatment on HPV-infected human being cervical tumor cells in addition to to review its results on HPV-associated oncogene manifestation. Preliminary testing of 29 artificial symmetrical diarylpentanoids was utilized to Vezf1 look for the potential cytotoxicity of the compounds on HeLa and CaSki cell growth. The selection process for candidate diarylpentanoids for in-depth studies prioritized compounds that dissolved well in dimethylsulfoxide (DMSO), were not strongly coloured (so as not to confound results from the colorimetric assay) and exhibited dose-dependent growth inhibitory effects compared to its untreated control. Based on these criteria, four compounds, 1,5-bis(4-hydroxy-3-methoxyphenyl)-1,4-pentadiene-3-one (MS13), 1,5-bis(2-hydroxyphenyl)-1,4-pentadiene-3-one (MS17), 1,5-bis(3-fluorophenyl)-1,4-pentadiene-3-one (MS40E) and 2,6-bis(3-fluorobenzylidene)cyclohexanone alpha-Hederin (MS49) were selected for further investigation. These four analogues were previously shown to display significant anti-proliferative activity and apoptotic properties when treated on androgen-independent human prostate cancer cells [41]. Its effects on HPV-infected human cervical cancer cells, however, are currently unknown. 2. Results and Discussion 2.1. Screening and Cytotoxicity of Diarylpentanoids 2.1.1. Diarylpentanoids Induce Cytotoxic Effects on HeLa and CaSki Cell Growth Between treated and non-treated HeLa cells (Physique 1), MS17 showed the most significant inhibition of cell growth with cell viability decreasing to 36% from a dose as low as 3.1 M and gradually decreasing to 14% at 6.3 M and then to less than 10% cell viability from 12.5 to 100 M. MS13 follows closely in cytotoxicity with cell viability decreasing to approximately 12% beginning from 12.5 M and decreasing to below 10% beyond this dose. MS49 and MS40E show significant growth inhibition of approximately 75% beginning at 12.5 and 25 M respectively. MS17 showed more potent effects in CaSki (Physique 2) compared to HeLa cells, with significant reduction in cell viability beginning from 1.6 M (30%) followed by 90% reduction in CaSki cell viability from 3.1 to 100 M. MS13 followed a similar trend by exhibiting a significant decrease in cell growth beginning from 3.1 M (50%); dosing beyond 6.3C100 M displayed around 10% cell growth after treatment. MS40E showed significant growth inhibition from 6.3 M (80%) to100 M (90%) but MS49 only showed a similar effect from 12.5 M (20% cell viability) and 25C100 M (~10% cell viability) onwards. Open in a separate window Physique 1 The inhibitory effects of cell viability by curcumin, MS13, MS17, MS40E and MS49 in HeLa cancer cell line compared to untreated sample (CONT). Results are expressed as means of alpha-Hederin percentage cell viability and comparison between data sets performed using ANOVA. Experiments were performed in triplicates and results compared between three impartial experiments. Asterisks indicate statistically significant (* for 0.05, *** for 0.001, **** for 0.0001) differences between the means of values obtained with treated untreated cells. Error bars depict mean SEM. Open in a separate window Physique 2 The inhibitory effects of cell viability by curcumin, MS13, MS17, MS40E and MS49 in CaSki cancer cell line compared to untreated sample (CONT). Results are alpha-Hederin expressed as means of percentage cell viability and evaluation between data models performed using ANOVA. Tests had been performed in triplicates and outcomes likened between three indie experiments. Asterisks reveal statistically significant (* for 0.05, ** for 0.01, **** for 0.0001) differences between your means of beliefs obtained with treated neglected cells. Error pubs depict mean SEM. Curcumin alternatively only.
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