Azal Jumaa

Antiproliferative Potential of Linagliptin-Rivaroxaban Mixture in Cervical Cancer: Mechanistic Insights into Targeting Mutant MAPK, RAS kinase Signal Protein

Repositioning existing marketed drugs represents a viable strategy for identifying new anticancer agents. This study employed an approach that combined these drugs and examined their molecular mechanisms of action against cancer. This study evaluated the anticancer properties of the linagliptin-rivaroxaban mixture and its molecular anticancer mechanism by screening its ability to target the mutant MAPK-RAS kinase signal proteins. Following 24 and 72 hours of incubation, HeLa and human-derived adipose tissue (NHF) cell lines were utilized to investigate the anticancer and safety properties of a linagliptin-rivaroxaban mixture and cisplatin at concentrations between 0.1 and 1,000 µg/ml. A combination and selectivity index study assessed the potential synergistic effects between mixture ingredients and selective toxicity. Computational molecular docking simulations were employed to investigate the binding affinity of linagliptin and rivaroxaban to various mutant kinase signal proteins within the MAPK-RAS kinase pathway. The study results indicated that the combination of linagliptin and rivaroxaban significantly suppressed the growth of cervical cancer cells compared to the inhibitory effects of cisplatin, linagliptin, and rivaroxaban individually. Furthermore, the mixture cytotoxicity on the NHF cell line was significantly lower than that of cisplatin. The interaction between linagliptin and rivaroxaban exhibited synergistic cytotoxicity, as evidenced by the combination index score. The mixture exhibited selective cytotoxicity against cancer cells, suggesting a favorable toxicity index score. The outcomes of the molecular docking pilot study of diverse mutant MAPK-RAS kinase signal proteins with the mixture's ingredients are indicated. Linagliptin and rivaroxaban's best interactions were with mutant P38 MAPK and RAS kinase signal proteins, with docking scores of -7.9 kcal/mol and -8.7 kcal/mol, respectively. Regarding the study findings and the established pharmacokinetic and safety profiles of mixture drugs. The linagliptin-rivaroxaban mixture offers an attractive and safer alternative for cervical cancer treatment.

Impact of Esomeprazole, Ciprofloxacin and Their Combination on Cervical Cancer Cell Line Proliferation: A Focus on Heat Shock Protein 70 Modulation

This investigation aimed to evaluate the combined efficacy of ciprofloxacin and esomeprazole in inhibiting cervical cancer proliferation and their capacity to target heat shock protein 70 in vitro. The MTT assay was utilized to assess the anticancer properties of the ciprofloxacin-esomeprazole combination on the HeLa cervical cancer cell line. The human fibroblast cell line (HFF) is employed to assess the combination's safety. The assay was performed within 24 and 72 hours of incubation. Ciprofloxacin, esomeprazole, and their combination concentrations ranged from 0.1 to 1000 µg/ml, with the mixture containing 50% of the individual concentration of each medication when assessed individually. The study employed the selective toxicity index to assess the selectivity of the mixture for cancer cells. The combination index was utilized to evaluate the potential synergistic effects of ciprofloxacin and esomeprazole. This study utilizes computational molecular docking simulations to assess the binding affinity of Ciprofloxacin and esomeprazole to heat shock protein 70 (PDB code: 1hjo). The MTT assay and selective toxicity index results indicated that the combination of ciprofloxacin and esomeprazole selectively inhibited the proliferation of cervical cancer cells. The inhibitory effect depended on the concentration of the mixture and the incubation duration, with a diminished impact on the viability of the HFF cell line. The combination index study indicates that the interaction between ciprofloxacin and esomeprazole shows a synergistic effect at each incubation period. The computational molecular docking simulation indicated that ciprofloxacin and esomeprazole target Hsp 70, with docking scores of -7.4 kcal/mol and -7.3 kcal/mol, respectively. Our findings from the MTT assay, selective toxicity index, combination index, and computational docking simulations suggest that the combination of ciprofloxacin and esomeprazole is a promising option for treating cervical cancer, given their set adverse effects and pharmacokinetic profiles.

Synergistic Cytotoxic Impact of Linagliptin - Ciprofloxacin Combination on Cervical Cancer Cell Line: Insights into Targeting Heat Shock Protein 60

This study aimed to assess the combined impact of linagliptin and ciprofloxacin on inhibiting cervical cancer cell line proliferation and their ability to target heat shock protein 60. The anticancer properties of the linagliptin-ciprofloxacin combination were assessed employing the HeLa cervical cancer cell line, with incubation periods of 24 and 72 hours. The human fibroblast cell line (HFF) was utilized to evaluate the mixture's safety. The concentrations of linagliptin, ciprofloxacin, and their combination varied between 0.1 and 1000 µg/ml. combination index value was estimated to assess the potential synergistic impact of linagliptin and ciprofloxacin. The study also employs computational molecular docking simulations to evaluate the affinity of linagliptin and ciprofloxacin for binding to heat shock protein 60. The study's findings demonstrated that the combination of linagliptin and ciprofloxacin markedly inhibited the proliferation of cervical cancer cells. The inhibitory effect depended on the concentration of the mixture and the incubation duration. It concurrently exhibits a diminished impact on the viability of the HFF cell line. The combination index study indicates that the interaction between linagliptin and ciprofloxacin shows a synergistic effect across all concentrations, particularly after 24 hours of incubation. The computational molecular docking simulation demonstrated that linagliptin and ciprofloxacin can bind with Hsp 60. The docking scores for linagliptin and ciprofloxacin were recorded at -7.6 kcal/mol and -8.1 kcal/mol, respectively. Our study findings from the MTT assay, combination index, and computational docking simulations indicate that the combination of linagliptin and ciprofloxacin presents a promising option for treating cervical cancer, considering their defined adverse effects and pharmacokinetic profiles.

Scrutiny of the Co-Cytotoxic Impact of Metformin-Omeprazole on the Cervical Cancer Cell Line and Their Aptitude to Target Heat Shock 60

This study aimed to assess the simultaneous effect of the metformin-omeprazole combination on inhibiting cervical cancer proliferation. Their ability to target heat shock protein 60. The anticancer properties of the metformin-omeprazole combination in cancer treatment were evaluated by employing a cervical cancer cell line (HeLa cell line). The assessment included two incubation periods: one of 24 hours and another of 72 hours. The concentrations of metformin, omeprazole, and their combination varied from 0.1 to 1000 µg/ml. The study encompassed an estimated combination index value to assess the potential synergistic effect of metronidazole and linagliptin. The study employs computational molecular docking simulation to determine the affinity of metformin and omeprazole for binding with heat shock protein 60. The study concluded that the metformin-omeprazole combination significantly reduced the proliferation of cervical cancer cells. The inhibitory effect was demonstrated to depend on the mixture's concentration and the treatment duration. The combination index indicates that metformin and omeprazole synergistically interacted. furthermore, the computational molecular docking simulation indicated that metformin and omeprazole exhibited a propensity to associate with Hsp 60. The docking scores for metformin and omeprazole were measured at -7.3 kcal/mol and -6.2 kcal/mol, respectively. Study indicates that the simultaneous use of metformin and omeprazole synergistically suppresses the growth of cervical cancer cells via both cell cycle-specific and cell cycle-nonspecific pathways. The findings, corroborated by molecular docking studies, demonstrated that metformin and omeprazole can bind to Heat Shock Protein 60. Furthermore, the molecular docking data elucidate the synergistic interactions among the combination components since every drug occupies a distinct binding site on Hsp 60, indicating a complementary binding mode with Hsp 60. Regarding the expected adverse impact and the known pharmacokinetic profile of the mixture's components, the mixture offered an attractive alternative treatment for cervical cancer.

Effect of Laetrile Vinblastine Combination on the Proliferation of the Hela Cancer Cell Line

This study aimed to evaluate the inhibitory effect of laetrile, vinblastine, and their mixture on cervical cancer cells and probe potential synergistic consequences. The study scrutinized the inhibitory impact of laetrile vinblastine and their mixture on the growth of human cervical cancer cells (Hela cancer cell line). The cells were incubated for 24, 48, and 72 hours with concentrations varying from 1 microgram to 10,000 micrograms of each substance. study results showed, the combination of vinblastine and laetrile effectively reduced the viability of human cervical cancer cells. This effect was stronger than the individual cytotoxic effects of each compound. The results suggest that the cytotoxicity of the vinblastine and laetrile combination increases with higher concentrations of the compounds. Additionally, the study revealed a synergistic effect between the mixture ingredients, particularly at the lowest and highest concentrations during the 24 and 72-hour incubation periods. The antiproliferative effect of (the combination of laetrile and vinblastine) was greater than the antiproliferative effect of either compound used alone, suggesting a synergistic relationship between the two.