Search

Objective: Lung cancer (LC) has the highest mortality rate globally. Most chemotherapeutic medicines now in use are cytotoxic, prompting the search for novel compounds with anticancer properties and improved safety profiles for normal cells. Dipeptidyl peptidase-4 inhibitors have demonstrated anticancer effects and apoptotic properties by specifically inhibiting dipeptidyl peptidase-4, a glycoprotein found in various organs that support the spread of cancer and tumor formation. Based on that, this study aimed to evaluate the cytotoxicity and apoptotic activity of sitagliptin (SITA) and linagliptin (LINA) against the lung cancer cell line (A549) alone and in combination with cisplatin (CP). Methods: A549 cells were categorized into six groups: control (untreated cells), CP-treated cells, SITA-treated cells, LINA-treated cells, CP plus SITA treated cells (1:1 ratio), and CP plus LINA treated cells (1:1 ratio). After 72 hours of incubation, cell viability (or cytotoxicity) and concentration required to inhibit 50% of cell viability (IC50) for each group were determined using an MTT assay. This method is safe and easy to use, has more reproducibility, and is commonly used for cell viability and cytotoxicity tests. Later, A549 cells were cultured in six flasks and exposed to the IC50 for 36 hours. Afterward, the cells were harvested and centrifuged, and the supernatant was removed. The remaining cell pellets were collected and lysed using a lysis buffer to measure B-cell lymphoma type 2 (BCL-2) levels with ELISA test kits. The data was collected and subjected to statistical analysis techniques. Results: MTT assay results determined that SITA and LINA significantly increased A549 cell cytotoxicity compared to the control group (P<0.0001). Moreover, combining SITA or LINA with CP showed markedly increased antitumor efficacy and more significant cytotoxicity directed toward A549 cells. Additionally, these combinations highly reduced IC50 in comparison to monotherapy. Considerably, both drugs showed remarkable apoptotic activity on A549 cells when used alone or combined with CP by decreasing BCL2 levels. Consequently, it potentiates apoptotic effects and cytotoxicity of CP against cancer cells. Interestingly, Lina was more potent than Sita regarding cytotoxicity and apoptotic activity on A549 cells. Conclusion: SITA and Lina exhibited significant cytotoxic and apoptotic effects against A549 cells through the induction of apoptosis. Notably, the results suggest a potential synergistic anticancer impact on CP. [ABSTRACT FROM AUTHOR]

Lung cancer has the highest global fatality rate of all cancers, and most existing therapies have a wide range of toxic effects. This necessitates searching for new medications with potential anticancer properties and a better safety profile against normal cells. Dipeptidyl peptidase-4 (DPP4) inhibitors have recently shown anticancer efficacy in various malignancies such as colorectal, prostate, and renal cancer. Therefore, this study investigated the anticancer activity of sitagliptin (SITA) and linagliptin (LINA) against the lung cancer cell line A549 alone and in combination with cisplatin (CP). A549 cells were divided into six groups: control (untreated cells), CP-treated cells, SITA-treated cells, LINA-treated cells, CP plus SITA-treated cells (ratio 1:1), and CP plus LINA-treated cells (ratio 1:1). After 72 hours of incubation, a 3-(4,5-dimethylthiazol2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) test was used to determine cell viability and the concentration of 50% inhibition for cell viability (IC50) for each group. A549 cells were later seeded in six flasks and treated with the resulting IC50; cell pellets were collected and lysed to determine the malondialdehyde (MDA) level using ELISA kits. SITA and LINA therapy dramatically reduced A549 cell viability compared to the control (P < 0.0001), with results comparable to CP. When SITA and LINA were combined with CP, they demonstrated significantly higher anticancer efficacy than when used alone. Notably, both medicines lowered MDA levels when taken alone or in combination with CP. SITA and LINA showed promising anticancer and antioxidant activity against A549 cells. This may indicate a potential synergistic anticancer effect with CP. [ABSTRACT FROM AUTHOR]

Lung cancer possesses the most significant worldwide mortality rate among all types of tumors, and the majority of current treatments exhibit a broad spectrum of adverse reactions. This requires investigating novel drugs that can inhibit the growth of cancer cells while minimizing harm to normal cells. Recent studies have demonstrated that Dipeptidyl peptidase-4 (DPP4) inhibitors can effectively suppress the growth of cancer cells in several types of malignancies, including colorectal, prostate, and kidney cancers. Hence, this study evaluated the effectiveness of sitagliptin in suppressing the proliferation of lung carcinoma cells (A549) alone as well as in conjunction with cisplatin. A549 cells were divided into four groups: control (untreated cells), cells treated with cisplatin, cells treated with sitagliptin, and cells treated with cisplatin plus sitagliptin combination (ratio 1:1). After incubation for 72 hours, a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl2H-tetrazolium bromide (MTT) test was utilized to evaluate cell viability percent and concentration of 50% inhibition for cell viability (IC50) for each group. Then, A549 cells were cultured into four flasks and exposed to the IC50 concentration. The resulting cell pellets were gathered and subjected to lysis to assess the malondialdehyde (MDA) level using ELISA kits. The vitality of A549 cells was significantly reduced by Sitagliptin therapy compared to the control (P < 0.0001). When the combination of sitagliptin and cisplatin was administered, it exhibited markedly superior anticancer effectiveness compared to their usage alone. Significantly, sitagliptin reduced MDA levels, whether used individually or in combination with cisplatin. As a result, sitagliptin exhibited significant anticancer and antioxidant properties against A549 cells. This suggests a possible synergistic anticancer effect with cisplatin. [ABSTRACT FROM AUTHOR]

Introduction In the human body, the adrenal cortex constitutes a major site for the biosynthesis and secretionofa varietyof steroid hormones including pregnenolone, dehydroepiandrosterone (DHEA), and androstenedione (Turcu et al. 2014). [...], The cytosolic sulfotransferase (SULT) SULT2A1 is known to mediate the sulfation of DHEA as well as some other hydroxysteroids such aspregnenolone. The present study was designedtoinvestigate how genetic polymorphismsof the human SULT2A1 gene may affect the sulfation of DHEA and pregnenolone. Online databases were systematically searched to identify human SULT2A1 single nucleotide polymorphisms (SNPs). Of the 98 SULT2A1 non-synonymous coding SNPs identified, seven were selected for further investigation. Site-directed mutagenesis was used to generate cDNAs encoding these seven SULT2A1 allozymes, which were expressed in BL21 Escherichia coli cells and purified by glutathione-Sepharose affinity chromatography. Enzymatic assays revealed that purified SULT2A1 allozymes displayed differential sulfating activity toward both DHEA and pregnenolone. Kinetic analyses showed further differential catalytic efficiency and substrate affinity of the SULT2A1 allozymes, in comparison with wild-type SULT2A1. These findings provided useful information concerning the effects of genetic polymorphisms on the sulfating activity of SULT2A1 allozymes. Key words: single nucleotide polymorphisms, cytosolic sulfotransferase, SULT, SULT2A1, sulfation, dehydroepiandrosterone, DHEA, pregnenolone. La sulfotransferase (SULT) cytosolique SULT2A1 est connue pour catalyser la sulfatation de la dehydroepiandrosterone (DHEA) de meme que d&apos;autres hydroxysteroides comme la pregnenolone. La presente etude a ete concue pour examiner comment les polymorphismes genetiques du gene SULT2A1 humain peuvent affecter la sulfatation de la DHEA et de la pregnenolone. Des bases de donnees en ligne ont ete systematiquement fouillees afin d&apos;identifier des polymorphismes mononucleotidiques (SNP) deSULT2A1 humain. Des 98 SNP codants non-synonymes de SULT2A1 identifies, sept ont ete choisis pour des etudes plus approfondies.La mutagenese dirigee aete utilisee pour generer des ADNc codant ces sept allozymes de SULT2A1, qui ont ete exprimees chez Escherichia coli BL21 et purifiees par chromatographie d&apos;affinite sur glutathion-Sepharose. Les dosages enzymatiques ont revele que les allozymes de SULT2A1 purifiees presentaient des activites de sulfatation differentielles envers la DHEA et la pregnenolone. Les analyses cinetiques ont en outre montre la differenciation de l&apos;efficacite catalytique et de l&apos;affinite pour les substrats des allozymes de SULT2A1, comparativement a SULT2A1 sauvage. Ces resultats ont fourni une information utile en ce qui concerne les effets des polymorphismes genetiques sur l&apos;activite de sulfatation des allozymes de SULT2A1. [Traduit par la Redaction] Mots-cles : polymorphismes mononucleotidiques, sulfotransferase cytosolique, SULT, SULT2A1, sulfatation, dehydroepiandrosterone, DHEA, pregnenolone.