6 research outputs found
An in vitro investigation of l-kynurenine, quinolinic acid, and kynurenic acid on B16 F10 melanoma cell cytotoxicity and morphology
No full textDATA AVAILABILITY STATEMENT : The data that support the findings of this study are available from the corresponding author upon reasonable request.The metastatic behavior of melanoma has accentuated the need for specific therapy
targets. Compounds, namely L‐kynurenine (L‐kyn), quinolinic acid (Quin), and kynurenic
acid (KA) previously displayed antiproliferative and cytotoxic effects in vitro against
cancer cells. Despite the growing interest in these compounds there are limited studies
examining the in vitro effects on melanoma. In B16 F10 melanoma cells, RAW 264.7
macrophage cells, and HaCat keratinocyte cells, postexposure to the compounds, crystal
violet staining was used to determine the half‐maximal inhibitory concentration (IC50),
whereas polarization‐optical transmitted light differential interference contrast and light
microscopy after hematoxylin and eosin (H&E) staining was used to assess morphological
changes. L‐kyn, Quin, and KA‐induced cytotoxicity in all cell lines, with L‐kyn being the
most cytotoxic compound. L‐kyn and KA at IC50‐induced morphological changes in B16
F10, RAW 264.7, and HaCat cell lines, whereas Quin had effects on B16 F10 and RAW
264.7 cells but did not affect HaCat cells. L‐kyn, Quin, and KA each display different
levels of cytotoxicity, which were cell line specific. L‐kyn was shown to be the most
potent compound against all cell lines and may offer future treatment strategies when
combined with other viable treatments against melanoma.The University of Pretoria and the National Research Foundation (NRF).wileyonlinelibrary.com/journal/cbfam2024AnatomyPhysiologySDG-03:Good heatlh and well-bein
L-kynurenine and quinolinic acid inhibited markers of cell survival in B16 F10 melanoma cells in vitro
No full textDATA AVAILABILITY STATEMENT :
The data that support the findings of this study are available from the corresponding author upon reasonable request.Melanoma is an aggressive malignancy and remains a major cause of skin cancer mortality, highlighting the need for new treatment strategies. Recent findings revealed that L-kynurenine and quinolinic acid induce cytotoxicity and morphological changes in B16 F10 melanoma cells in vitro. This paper highlights the effects of L-kynurenine and quinolinic acid at previously determined half-maximal inhibitory concentrations on cell cycle progression, cell death and extracellular signal-regulated protein kinase inhibition. Melanoma, B16 F10 and murine macrophages, RAW 264.7 cells were used in this study, as both cell lines express all the enzymes associated with the kynurenine pathway. Post exposure to the compounds at half-maximal inhibitory concentrations, transmission electron microscopy was used to assess intracellular morphological changes. Flow cytometry was used to analyse cell cycle progression and quantify apoptosis via the dual staining of Annexin V and propidium iodide and cell survival via extracellular signal-regulated protein kinase. L-kynurenine and quinolinic acid at half-maximal inhibitory concentrations induced intracellular morphological changes representative of cell death. Flow cytometry revealed alterations in cell cycle distribution, increased apoptosis and significantly inhibition of cell survival. L-kynurenine and quinolinic acid are exogenous kynurenine compounds which inhibited cell survival through extracellular signal-regulated protein kinase inhibition, induced cell cycle alterations and induced apoptosis in B16 F10 melanoma cells.
SIGNIFICANCE STATEMENT : Data obtained in the current study revealed information regarding the in vitro effects of L-kynurenine and quinolinic acid on B16 F10 melanoma cell cycle progression, intracellular morphology, extracellular signal-regulated kinase 1/2 inhibition and cell death. Evaluating the therapeutic effects of kynurenine metabolites against melanoma may potentially result in improved future cancer treatment options to manage the global melanoma burden.National Research Foundation;
Struwig-Germeshuysen Kankernavorsingstrust;
RESCOM;
RDP.https://onlinelibrary.wiley.com/journal/10958355hj2024AnatomyPhysiologySDG-03:Good heatlh and well-bein
An exploratory study on the effect of kynurenine metabolites on sEnd-2 endothelioma cells
No full textDATA AVAILABILITY STATEMENT :
The data that support the findings of this study are available from the corresponding author upon reasonable request.Cancer is the second leading cause of mortality worldwide. The development of anticancer therapy plays a crucial role in mitigating tumour progression and metastasis. Epithelioid hemangioendothelioma is a very rare cancer, however, with a high systemic involvement. Kynurenine metabolites which include l-kynurenine, 3-hydroxykynurenine, 3-hydroxyanthranilic acid and quinolinic acid have been shown to inhibit T-cell proliferation resulting in a decrease in cell growth of natural killer cells and T cells. Furthermore, metabolites such as l-kynurenine have been shown to inhibit proliferation of melanoma cells in vitro. Considering these metabolite properties, the present study aimed to explore the in vitro effects of l-kynurenine, quinolinic acid and kynurenic acid on endothelioma sEnd-2 cells and on endothelial (EA. hy926 cells) (control cell line). The in vitro effect at 24, 48, and 72 h exposure to a range of 1−4 mM of the respective kynurenine metabolites on the two cell lines in terms of cell morphology, cell cycle progression and induction of apoptosis was assessed. The half inhibitory concentration (IC50), as determined using nonlinear regression, for l-kynurenine, quinolinic acid and kynurenic acid was 9.17, 15.56, and 535.40 mM, respectively. Optical transmitted light differential interference contrast and hematoxylin and eosin staining revealed cells blocked in metaphase, formation of apoptotic bodies and compromised cell density in l-kynurenine-treated cells. A statistically significant increase in the number of cells present in the sub-G1 phase was observed in l-kynurenine-treated sample. To our knowledge, this was the first in vitro study conducted to investigate the mechanism of action of kynurenine metabolites on endothelioma sEnd-2 cells. It can be concluded that l-kynurenine exerts an antiproliferative effect on the endothelioma sEnd-2 cell line by decreasing cell growth and proliferation as well as a metaphase block. These hallmarks suggest cell death via apoptosis. Further research will be conducted on l-kynurenine to assess the effect on cell adhesion in vitro and in vivo as cell-cell adhesion has been shown to increase metastasis to distant organs therefore, the inhibition of adhesion may lead to a decrease in metastasis.The National Research Foundation (NRF) and the University Capacity Development Programme (UCDP).https://wileyonlinelibrary.com/journal/cbfhj2024AnatomyPhysiologySDG-03:Good heatlh and well-bein
Multiple antidiabetic effects of three α-glucosidase inhibitory peptides, PFP, YPL and YPG : Dipeptidyl peptidase–IV inhibition, suppression of lipid accumulation in differentiated 3T3-L1 adipocytes and scavenging activity on methylglyoxal
No full textAntidiabetic agents with multiple targets have the greatest pharmaceutical potential. In this study, three α-glucosidase inhibitory peptides, PFP, YPL and YPG, were investigated for additional antidiabetic targets viz.; dipeptidyl peptidase-IV inhibition (DPP-IV), lipid accumulation and the differentiation of 3T3-L1 adipocytes, and scavenging of methylglyoxal (MGO), reactive oxygen species (ROS) and nitric oxide (NO). The peptides were subjected to molecular docking on human DPP-IV where the binding free energies were PFP < YPG < YPL < diprotin A while hydrogen bond interactions were critical in the binding of YPL and YPG. Moreover, YPG demonstrated significantly higher (p < 0.05) in vitro DPP-IV inhibition than PFP and YPL. Kinetic analysis revealed that all three peptides are uncompetitive inhibitors of DPP-IV while YPG had the lowest inhibition binding constant. PFP and YPG prevented lipid accumulation in 3T3-L1 differentiated adipocytes but may be due to cytotoxicity for PFP. The peptides scavenged MGO, ROS and NO but only the ROS and NO scavenging activities of YPG were comparable to glutathione. In conclusion, PFP, YPL and YPG exhibited DPP-IV inhibitory activity, reduced adipocyte differentiation and lipid accumulation as well as scavenged MGO, ROS and NO. However, YPG had the best potential as a possible multifunctional antidiabetic agent.The National Research Foundation of South Africa and the University of Pretoria. The first author also acknowledges the University of Pretoria for the award of a postdoctoral fellowship position in Biochemistry and Ahmadu Bello University, Zaria, Nigeria for the award of a study fellowship.http://www.elsevier.com/locate/ijbiomac2020-02-01hj2018AnatomyBiochemistryGeneticsMicrobiology and Plant Patholog
Bioactive peptides from African yam (AVIAIMF and GPADPF) and taro (NGDF and NGNW) reveal multifunctional antidiabetic effects using biochemical and cellular models
No full textDATA AVAILABILITY : The data that support the findings of this study are available from the corresponding author upon reasonable request.The multifactorial nature of type 2 diabetes mellitus (T2DM) has driven a need to discover multifunctional antidiabetic peptides preferably from functional food sources for possible application as antidiabetic supplements. Herein, the antidiabetic effects of bioactive peptides previously identified in yam (AVIAIMF & GPADPF) and taro (NGDF & NGNW) were investigated. The peptides showed significantly (p < 0.05) higher dipeptidyl peptidase IV inhibitory activities than vildagliptin with NGDF having the best activity. AVIAIMF, GPADPF, and NGNW significantly inhibited the formation of methylglyoxal-induced advanced glycosylated end products (AGEs) while AVIAIMF and NGNW showed oxygen radical scavenging (ORAC) activities. The peptides also showed significant (p < 0.05) nitric oxide (NO) scavenging activities in murine macrophage (RAW 264.7) cells and were not cytotoxic to the RAW 264.7 cells in the presence and absence of lipopolysaccharide. The peptides did not show a biologically significant inhibition of lipid formation in 3T3-LI adipocytes and were not cytotoxic to human colon adenocarcinoma (Caco-2) cells, suggesting safety. The ORAC negatively correlated (− 0.40) with % AGEs formed and positively correlated (0.53 and 0.41) with the viability of LPS + and LPS- RAW 264.7 cells respectively. AVIAIMF, GPADPF and NGNW have shown promising multifunctional anti-T2DM activities that could be considered as potential antidiabetic peptides for application in functional antidiabetic foods.Institutional Based Grant by the Tertiary Education Fund.https://link.springer.com/journal/109892024-04-29AnatomyBiochemistryGeneticsMicrobiology and Plant PathologySDG-03:Good heatlh and well-bein
The implementation of tuberculosis preventive therapy in HIV care clinics in Africa, Asia and Latin America: a multiregional site survey
No full textIntroduction Towards the ‘End TB Strategy’ targets, the WHO recommends the provision of tuberculosis (TB) preventive therapy (TPT) for high-risk groups including people living with HIV (PLWH). 3 years after the release of the updated 2020 WHO guidelines, we investigated the implementation of TPT services at HIV clinics in low-income and middle-income countries (LMICs), focusing on TB screening, populations eligible for TPT and available TPT regimens.Methods In 2023, we surveyed HIV care clinics in the International Epidemiology Databases to Evaluate AIDS consortium in Africa, the Asia-Pacific and Latin America and the Caribbean. We used descriptive statistics to summarise TPT implementation according to WHO guidelines and multivariable logistic regression models to estimate associations with clinic characteristics.Results Of 172 HIV clinics included, 142 (83%) were in Africa, 22 (13%) in the Asia-Pacific and 8 (5%) in Latin America; 108 (63%) were located in urban areas. After ruling out active TB, TPT was reportedly offered to PLWH (122 clinics, 71%), household contacts of individuals with active TB (120 clinics, 70%) and other high-risk populations. TPT for PLWH was more frequently available in clinics in lower-income and low-middle-income countries, in high TB burden countries, and in district hospitals compared with other facility types. Clinics reported use of isoniazid-based (160 clinics, 93%) and shorter rifamycin-based (129 clinics, 75%) TPT regimens. Reported barriers to TPT initiation included patient refusal at 71 (41%) and drug shortages at 67 (39%) clinics.Conclusions TPT was available at most HIV care clinics in LMICs but further efforts are needed to reinforce WHO recommendations and ensure that TPT is consistently accessible to people at higher risk of developing active TB, especially PLWH
