Chemical Inhibition of RPA by HAMNO Alters Cell Cycle Dynamics by Impeding DNA Replication and G2-to-M Transition but Has Little Effect on the Radiation-Induced DNA Damage Response.

Replication protein A (RPA) is the major single-stranded DNA (ssDNA) binding protein that is essential for DNA replication and processing of DNA double-strand breaks (DSBs) by homology-directed repair pathways. Recently, small molecule inhibitors have been developed targeting the RPA70 subunit and preventing RPA interactions with ssDNA and various DNA repair proteins. The rationale of this development is the potential utility of such compounds as cancer therapeutics, owing to their ability to inhibit DNA replication that sustains tumor growth. Among these compounds, (1Z)-1-[(2-hydroxyanilino) methylidene] naphthalen-2-one (HAMNO) has been more extensively studied and its efficacy against tumor growth was shown to arise from the associated DNA replication stress. Here, we study the effects of HAMNO on cells exposed to ionizing radiation (IR), focusing on the effects on the DNA damage response and the processing of DSBs and explore its potential as a radiosensitizer. We show that HAMNO by itself slows down the progression of cells through the cell cycle by dramatically decreasing DNA synthesis. Notably, HAMNO also attenuates the progression of G2-phase cells into mitosis by a mechanism that remains to be elucidated. Furthermore, HAMNO increases the fraction of chromatin-bound RPA in S-phase but not in G2-phase cells and suppresses DSB repair by homologous recombination. Despite these marked effects on the cell cycle and the DNA damage response, radiosensitization could neither be detected in exponentially growing cultures, nor in cultures enriched in G2-phase cells. Our results complement existing data on RPA inhibitors, specifically HAMNO, and suggest that their antitumor activity by replication stress induction may not extend to radiosensitization. However, it may render cells more vulnerable to other forms of DNA damaging agents through synthetically lethal interactions, which requires further investigation.

Artichoke as a melanoma growth inhibitor.

Melanoma is the most lethal malignancy in skin cancers. About 97,610 new cases of melanoma are projected to occur in the United States (US) in 2023. Artichoke is a very popular plant widely consumed in the US due to its nutrition. In recent years, it has been shown that artichoke shows powerful anti-cancer effects on cancers such as breast cancer, colon cancer, liver cancer, and leukemia. However, there is little known about its effect on melanoma. This study was designed to investigate if artichoke extract (AE) has any direct effect on the growth of melanoma. Clonogenic survival assay, cell proliferation, and caspase-3 activity kits were used to evaluate the effects AE has on cell survival, proliferation, and apoptosis of the widely studied melanoma cell line HTB-72. We further investigated the possible molecular mechanisms using RT-PCR and immunohistochemical staining. The percentage of colonies of HTB-72 melanoma cells decreased significantly after treated with AE. This was paralleled with the decrease in the optic density (OD) value of cancer cells after treatment with AE. This was further supported by the decreased expression of PCNA mRNA after treated with AE. Furthermore, the cellular caspase-3 activity increased after treated with AE. The anti-proliferative effect of AE on melanoma cells correlated with increased p21, p27, and decreased CDK4. The pro-apoptotic effect of AE on melanoma cells correlated with decreased survivin. Artichoke inhibits growth of melanoma by inhibition of proliferation and promotion of apoptosis. Such a study might be helpful to develop a new promising treatment for melanoma.

Olive: A Potential Suppressor for Cervical Cancer by Upregulation of P21.

Background Cervical cancer is the second deadliest for women between the ages of 20 and 39 years. Even with prevention tactics for screening, incident rates and mortality of cervical cancer remain high. Olive has been shown to have many beneficial effects in humans concerning cardiovascular disease and inflammation. Despite these promising benefits, little is known about its effect on cervical cancer. This study examined the effects and mechanism of effects of olive extract (OE) on the HeLa cervical cancer cell line. Methodology We utilized clonogenic survival assay, quick cell proliferation assay, and caspase-3 activity to investigate the effect of OE on the proliferation and apoptosis of the cervical cancer cell line HeLa. To investigate the mechanisms behind these findings, Reverse transcription polymerase chain reaction and immunohistochemistry were performed. Results OE inhibited the growth and proliferation of HeLa cells. In comparison to the control, the percentage of colonies, as well as the optical density of the cervical cancer cells, was found to be decreased. In addition, the relative activity of caspase-3, a marker for apoptosis, was increased after treatment with OE. The anti-proliferative effect of OE on HeLa cells correlated with the increase of an anti-proliferative molecule p21. However, the pro-apoptotic effect of OE was not correlated with the change in major pro-apoptotic or anti-apoptotic molecules examined in this study. Conclusions Our study suggests that OE inhibits the growth of HeLa cervical cancer cells by upregulation of p21. Further investigation of the effects of OE on cervical cancer and other cancers is warranted by these results.

Say 'No' to Cancer and 'Yes' to Cranberry: The Role of Cranberry Extract in Inhibition of Growth of Lung Adenocarcinoma Cells.

BACKGROUND/AIM: Lung cancer is the leading cause of mortality due to cancer death. Treatment of lung adenocarcinoma (LUAD) is still challenging. Cranberries contain many rich bioactive components that may help fight cancer. The action of cranberry against some cancer types has been reported, however, its role in lung cancer has only been investigated in large-cell lung cancer. In this study, we expanded current research on the role of cranberry in LUAD. MATERIALS AND METHODS: A549 LUAD cancer cells were treated with commercial cranberry extract (CE). Proliferation of A549 cells was measured with a clonogenic survival assay and quick proliferation assay. Caspase-3 activity was used to evaluate apoptosis of A549 cells. Reverse transcriptase-polymerase chain reaction was conducted to investigate the possible molecular mechanisms involved in the action of CE. RESULTS: Treatment of LUAD with CE reduced the percentage of A549 colonies. This was consistent with the decrease in the optic density of cancer cells after treatment with CE. Caspase-3 activity increased after treatment with CE. The anti-proliferative effect of CE on A549 cells correlated with reduced expression of pro-proliferation molecules cyclin E, cyclin-dependent kinase 2 (CDK2) and CDK4. The pro-apoptotic effect of CE on A549 cells correlated with the reduced expression of the anti-apoptotic molecule caspase 8 and FADD-like apoptosis regulator (FLIP). CONCLUSION: CE had an inhibitory effect on the growth of LUAD cells by modulation of both pro-proliferative and anti-apoptotic molecules. Our research hopes to guide future treatment options for LUAD.

The Novel Use of IL-28 as an Effective Radiosensitizer in Pancreatic Cancer.

BACKGROUND/AIM: Pancreatic cancer is the second most common gastrointestinal cancer in the world, yet the five-year survival outcome rate of less than 5% urges for improvement in medical interventions of pancreatic cancer. Currently, high dose radiation therapy (RT) is used as an adjuvant treatment; however, the high level of RT required to treat advanced neoplasms leads to high incidence rates of side effects. In recent years, the utilization of cytokines as radiosensitizing agents has been studied, in order to reduce the amount of radiation required. However, few studies have examined IL-28 regarding its potential as a radiosensitizer. This study is the first to utilize IL-28 as a radiosensitizing agent in pancreatic cancer. MATERIALS AND METHODS: MiaPaCa-2, a widely used pancreatic cancer cell line was used in this study. Clonogenic survival and cell proliferation assays were used to evaluate growth and proliferation of MiaPaCa-2 cells. Caspase-3 activity assay was used to evaluate apoptosis of MiaPaCa-2 cells and RT-PCR was used to study the possible molecular mechanisms. RESULTS: Our results showed that IL-28/RT enhanced RT-induced inhibition of cell proliferation and promoted apoptosis of MiaPaCa-2 cells. Furthermore, compared to RT alone, we found that IL-28/RT up-regulated the mRNA expression of TRAILR1 and P21, while down-regulating mRNA expression of P18 and survivin in MiaPaCa-2 cells. CONCLUSION: IL-28 has the potential to be used as a radiosensitizer for pancreatic cancer and warrants further investigation.

IL-32 and its paradoxical role in neoplasia.

Interleukin-32 (IL-32) is an interleukin cytokine usually linked to inflammation. In recent years, it has been found that IL-32 exhibits both pro- and anti-tumor effects. Although most of those effects from IL-32 appear to favor tumor growth, some isoforms have shown to favor tumor suppression. This suggests that the role of IL-32 in neoplasia is very complex. Thus, the role of IL-32 in these various cancers and protein pathways makes it a very crucial component to consider when looking at potential therapeutic options in tumor treatment. In this review, we will explore what is currently known about IL-32, including its relationship with tumorigenesis and the potential for IL-32 to enhance local and systemic anti-tumor immune responses. Such a study might be helpful to accelerate the development of IL-32-based immunotherapies.

The past, present, and future of immunotherapy for bladder tumors.

Bladder cancer is a prominent cancer worldwide with a relatively low survival rate for patients with increased stage and metastasis. Current treatments are based on surgical removal, bacillus Calmette-Guerin (BCG) Immunotherapy, and platinum-based chemotherapy. However, treatment resistance due to genetic instability of bladder tumors, as well as intolerance to treatment adverse effects leads to the necessity to further treatment options. New advancements in immunotherapy are on the rise for treatment of various cancers and specifically has shown promise in the treatment of bladder cancer. This review summarizes these new advancements in treatment options involving cytokines and cytokine blockade. Such a study might be helpful for urologists to manage patients with bladder cancer more effectively.

Environmental, energy, and economic impact assessment of sludge management alternatives based on incineration.

In this study, different management strategies for sewage sludge disposal were evaluated associated with environmental, energy, and economic impact, using life cycle assessment (LCA), cumulative energy demand (CED) and life cycle costing (LCC) approaches. Four scenarios, including mono-incineration, co-incineration in municipal solid wastes (MSW) incineration plant, co-incineration in coal-fired power plant and co-incineration in cement kiln, were assessed. The environmental burdens generated from the sludge incineration contributed primarily to the global warming, followed by eutrophication, marine aquatic ecotoxicity, and human toxicity potential across the four scenarios. Furthermore, mono-incineration scenario appeared to be the most environmentally unfriendly, energy and economy intensive alternative, with the LCA, CED and LCC value of 5.41E-09, 1736 MJ and 1.84 million CNY, respectively. By contrast, co-incineration in cement kiln exhibited the lowest CED (368 MJ), LCC (0.59 million CNY), and environmental burdens (1.02E-09). In addition, the sensitivity analysis indicated that four scenarios were sensitive to the changes in the electricity efficiency and the moisture content contained in sewage sludge, suggesting that it was of great significance to enhance the efficiency of sludge dewatering and thermal drying The findings of this study can provide scientific reference for selecting the optimal strategies for the most environmentally and economically friendly sewage sludge management with optimum energy efficiency.

Immunotherapy for Non-small Cell Lung Cancer: Current Agents and Potential Molecular Targets.

From radiation therapy and surgery to chemotherapy and targeted therapy, the treatment of non-small cell lung cancer (NSCLC) has remarkably evolved over the past few decades. In recent years, immunotherapy has become an increasingly attractive area of interest in the treatment of NSCLC, especially those in advanced stages. Cytokine and immune checkpoint inhibitors are among the most studied immunotherapies for many cancer types. Herein, we provide an overview of current popular cytokine and checkpoint inhibitor treatment regimens available for patients with NSCLC. Ongoing clinic trials and novel molecular targets that are discussed here could lead to promising new treatment options for NSCLC. The evidence summarized in this review might be helpful for clinicians to better manage patients with NSCLC.

Increased Resection at DSBs in G2-Phase Is a Unique Phenotype Associated with DNA-PKcs Defects That Is Not Shared by Other Factors of c-NHEJ.

The load of DNA double-strand breaks (DSBs) induced in the genome of higher eukaryotes by different doses of ionizing radiation (IR) is a key determinant of DSB repair pathway choice, with homologous recombination (HR) and ATR substantially gaining ground at doses below 0.5 Gy. Increased resection and HR engagement with decreasing DSB-load generate a conundrum in a classical non-homologous end-joining (c-NHEJ)-dominated cell and suggest a mechanism adaptively facilitating resection. We report that ablation of DNA-PKcs causes hyper-resection, implicating DNA-PK in the underpinning mechanism. However, hyper-resection in DNA-PKcs-deficient cells can also be an indirect consequence of their c-NHEJ defect. Here, we report that all tested DNA-PKcs mutants show hyper-resection, while mutants with defects in all other factors of c-NHEJ fail to do so. This result rules out the model of c-NHEJ versus HR competition and the passive shift from c-NHEJ to HR as the causes of the increased resection and suggests the integration of DNA-PKcs into resection regulation. We develop a model, compatible with the results of others, which integrates DNA-PKcs into resection regulation and HR for a subset of DSBs. For these DSBs, we propose that the kinase remains at the break site, rather than the commonly assumed autophosphorylation-mediated removal from DNA ends.

Mangosteen Inhibits Growth and Survival of Cervical Cancer Cells.

BACKGROUND: Cervical cancer is the most common cancer of the female reproductive system. Late-stage cervical cancer treatment has been largely unsuccessful, and urgent anti-cancer therapy is needed. Mangosteen, a tropical fruit, has been studied and found to be rich in xanthones, known anti-cancer compounds. This study was designed to investigate the effect of mangosteen extract (ME) on SiHa cervical cancer cells and to explore the underlying molecular mechanisms. MATERIALS AND METHODS: Clonogenic survival assay, Quick Cell Proliferation Assay, terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) staining, and caspase-3 activity kits were used to investigate the in vitro role of ME treatment in SiHa cervical cancer cell growth. We further investigated the possible molecular mechanisms using RT-PCR. Statistical analysis was done with unpaired two-tailed Student's t-test and significance at p-value <0.05; each experiment was repeated three times. RESULTS: Our study found that the growth and proliferation of SiHa cervical cancer cells was inhibited by ME. ME also induced apoptosis in SiHa cervical cancer cells. The anti-proliferative effect of ME on cervical cancer cells was associated with statistically significant (p<0.05) down-regulation of the pro-proliferative molecules cyclin B, cyclin D and cyclin E. The pro-apoptotic effect of ME was associated with statistically significant (p<0.05) down-regulation of the anti-apoptotic molecules flice-like inhibitory protein (FLIP) and survivin. CONCLUSION: ME impedes the growth and survival of SiHa cervical cancer cells by down-regulating cyclin B, cyclin D, cyclin E as well as FLIP and survivin. ME may be a promising strategy for targeted cancer immunotherapy development.

The Effect of Asparagus Extract on Pancreatic Cancer: An Intriguing Surprise.

BACKGROUND: Pancreatic cancer is the most lethal digestive cancer and the fourth overall cause of cancer death in the US. Asparagus, a widely consumed savory vegetable, is a rich source of antioxidants, saponins, vitamins, and minerals. In recent years, it has been shown that components of asparagus have anticancer effects on endometrial adenocarcinoma, and in prostate, breast, and colon cancer. In pancreatic cancer, it has been shown to have an anticancer effect on the KLM1-R cell line. This study was designed to investigate if asparagus extract (AE) had any effect on the growth of a widely used pancreatic cancer cell line MDAPanc-28 and to elucidate possible molecular mechanisms behind it. MATERIALS AND METHODS: Clonogenic survival assay, proliferation, and caspase-3 activity kits were used to evaluate the effects of AE on cell survival, proliferation, and apoptosis pathway of MDAPanc-28 cells. We further investigated the possible molecular mechanisms by using reverse transcription-polymerase chain reaction. RESULTS: The colony numbers and proliferation of MDAPanc-28 cells were surprisingly increased when treated with AE. The relative caspase-3 activity in cancer cells decreased when they were treated with AE. The pro-proliferative effect of AE on MDAPanc-28 cells correlated with down-regulation of anti-proliferative molecules P21 and P53. The potential anti-apoptotic effect of AE correlated with down-regulation of the pro-apoptotic molecule Fas cell surface death receptor (FAS) and down-regulation of caspase-3 activity. CONCLUSION: AE exhibits a pro-tumor effect on MDAPanc-28 pancreatic cancer cells by down-regulation of P21, P53, and FAS.

Slater-Koster parametrization for the phonons of monolayer MoX2(X = S, Se or Te).

With the help of the Slater-Koster parametrization, we construct simplified force constant (FC) models to describe the phonons of several two-dimensional (2D) transition metal dichalcogenides (TMDs) (MoX2, X = S, Se or Te) by only considering the FCs to fourth-nearest-neighbor interactions. By fitting the phonon dispersions derived from first-principles calculations, we find these models can well describe the symmetry characters and semimetal states of MoX2's phonons. Combining the basis of the FC model and the theory of tensor representation, we derive the origin of the irreducible representations at the high symmetry points Γ,KandM. Moreover, by using the compatibility relation between high symmetry points and high symmetry lines, we find the semimetal states of MoX2are protected by vertical and horizontal mirrors. Our work provides an effective tool to further study the phonons of 2D TMDs.

SARS-CoV-2 spike protein inhibits growth of prostate cancer: a potential role of the COVID-19 vaccine killing two birds with one stone.

To investigate the effects of isolated SARS-CoV-2 spike protein on prostate cancer cell survival. The effects of SARS-CoV-2 spike protein on LNCaP prostate cancer cell survival were assessed using clonogenic cell survival assay, quick cell proliferation assay, and caspase-3 activity kits. RT-PCR and immunohistochemistry were performed to investigate underlying molecular mechanisms. SARS-CoV-2 spike protein was found to inhibit prostate cancer cell proliferation as well as promote apoptosis. Further investigation revealed that anti-proliferative effects were associated with downregulation of the pro-proliferative molecule cyclin-dependent kinase 4 (CDK4). The increased rate of apoptosis was associated with the upregulation of pro-apoptotic molecule Fas ligand (FasL). SARS-CoV-2 spike protein inhibits the growth of LNCaP prostate cancer cells in vitro by a two-pronged approach of downregulating the expression of CDK4 and upregulating FasL. The introduction of SARS-CoV-2 spike protein into the body via COVID-19 vaccination may have the potential to inhibit prostate cancer in patients. This potential beneficial association between COVID-19 vaccines and prostate cancer inhibition will require more extensive studies before any conclusions can be drawn about any in vivo effects in a human model.

Multijointed Pneumatic Soft Hand with Flexible Thenar.

Soft robotic hands provide better safety and adaptability than rigid robotic hands. Furthermore, a multijointed structure that imitates the movement of a human hand represents significant progress in realizing its anthropomorphism. In this study, we present a multijointed pneumatic soft anthropomorphic hand that is capable of expressing letters through sign language and grasping different objects using three grasping modes, namely thumb grasping, precision grasping, and power grasping. This novel soft hand is composed of multijointed soft fingers, a thumb, thenar, and 3D-printed palm. Tests were performed to characterize the displacement track and force performance of the fingers, thumb, and thenar, which was made by mold casting silicone rubber. In addition, a dedicated pneumatic control system was designed and built to enable the soft hand to automatically perform the tasks set by specific programs. This new multijointed hand with a flexible thenar represents significant progress in the development of anthropomorphic bionic hands, offering the benefits of fast response, low cost, as well as ease of fabrication, assembly, and replacement.

Harnessing the Power of Kiwifruit for Radiosensitization of Melanoma.

BACKGROUND: Melanoma is the deadliest variant of skin cancer and its incidence continues to increase. There are limited treatment options for advanced and metastatic cases of melanoma, despite advances in immunotherapy and chemotherapy. Melanoma is notorious as a radioresistant tumor. Previous studies found that phytochemicals, such as resveratrol and those found in green tea and blueberry, can sensitize various cancer cells, including melanoma, to radiotherapy. Our previous study also revealed that kiwifruit extract (KE) has antitumor activity to melanoma cells. This study was designed to expand upon our previous investigation and determine KE's potential as a radiosensitizer on CRL-11147 melanoma cancer cells and elucidate the possible mechanisms behind its potential. MATERIALS AND METHODS: Proliferation and apoptosis of CRL-11147 melanoma cells under radiation therapy (RT) plus KE versus RT alone were investigated using Proliferative cell nuclear antigen (PCNA) staining, quick cell proliferation assay, clonogenic assay, and caspase-3 activity assay. Reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC) were then used to investigate the mechanisms behind the observed results. RESULTS: The percentage of CRL-11147 colonies, PCNA staining intensity, and the optic density value of CRL-11147 cells decreased with RT/KE vs. RT alone. Relative caspase-3 activity was increased with RT/KE vs. RT alone. Increased expression of the anti-proliferative molecule p27 and pro-apoptotic molecule TRAILR1 correlated with the anti-tumor effect seen in the RT/KE group versus the RT alone group. CONCLUSION: KE augments radiosensitivity of CRL-11147 by up-regulating both p27 and TRAILR1 to inhibit proliferation and increase apoptosis, respectively.

AFP peptide (AFPep) as a potential growth factor for prostate cancer.

Prostate cancer is the most common cancer among men in the USA. A peptide derived from the active site of alpha-fetoprotein (AFP), known as AFPep, has been shown to be efficacious in inhibiting breast cancer growth. The role of this derived peptide AFPep in the development of prostate cancer has yet to be studied. To investigate the role of AFPep on prostate cancer, we used the PC-3 and DU-145 cell lines. We found that through key anti-apoptosis and pro-proliferation molecules, AFPep enhances the proliferation of DU-145 prostate cancer cells. The anti-proliferative molecules p18, p21, and p27, along with the pro-apoptotic molecules Fas and Bax, were all down-regulated in DU-145 cell lines treated with AFPep. Conversely, AFPep was not found to have a proliferative effect on the PC-3 prostate cancer cell line. This finding suggests the effects of AFPep to be cell line-specific in prostate cancer. Further investigation into the effects of AFPep could lead to new areas of treating prostate cancer.

Cranberry Extract Is a Potent Radiosensitizer for Glioblastoma.

BACKGROUND/AIM: Glioblastoma, also known as glioblastoma multiforme (GBM), is the most aggressive type of primary brain tumor and a cornerstone in its treatment is radiotherapy (RT). However, RT for GBM is largely ineffective at clinically safe doses, thus, the study of radiosensitizers is of great significance. MATERIALS AND METHODS: With accumulating evidence for the anticancer effect of compounds from cranberry, this study was designed to investigate if cranberry extract (CE) sensitizes GBM to RT in the widely used human glioblastoma cell line U87. We utilized clonogenic survival assays, cell proliferation assays, and caspase-3 activity kits. Potential proliferative and apoptotic molecular mechanisms were evaluated by reverse transcription-polymerase chain reaction. RESULTS: We found that CE alone had little effect on the survival of U87 cells. However, RT supplemented by CE significantly inhibited proliferation and promoted apoptosis of U87 cells when compared with RT alone. The proliferation-inhibitory effect of RT/CE might be attributable to the up-regulation of p21, along with the down-regulation of cyclin B and cyclin-dependent kinase 4. This pro-apoptotic effect might additionally be attributable to the down-regulation of survivin. CONCLUSION: These results warrant further study of the potential radiosensitizing capacity of CE in glioblastoma and other cancer types.

Raspberry Extract With Potential Antitumor Activity Against Cervical Cancer.

BACKGROUND: Cervical cancer (CC) is one of the leading causes of mortality worldwide. Previously, we reported that blueberry extract constrains the growth of CC. Raspberry is a widely consumed fruit that exhibits antitumor properties against several cancer types but little is known about its direct effect on CC. This study was designed to investigate the potential antitumor effect of raspberry extract (RE) on CC cells and to elucidate the possible mechanisms behind it. MATERIALS AND METHODS: Clonogenic survival assay and caspase-3 activity kits were used to evaluate the effects of RE on cell survival, proliferation, and apoptosis of a widely used CC cell line, HeLa. Possible molecular mechanisms were investigated using reverse transcription-polymerase chain reaction. RESULTS: The percentage of colonies and optic density value of HeLa cells decreased in the presence of RE in comparison to controls. Relative caspase-3 activity in cancer cells increased in the presence of RE in comparison to controls. The antitumor effect displayed on HeLa cells by RE was associated with the increased expression of antiproliferative molecule P53 and the increased expression of pro-apoptotic molecule tumor necrosis factor receptor superfamily member 6 (FAS). CONCLUSION: RE displays anticancer activity against CC HeLa cells. The mechanism behind this is by up-regulation of anti-proliferative molecule P53 and pro-apoptotic molecule FAS.

IL-39 Reduces Proliferation and Promotes Apoptosis of Bladder Cancer by Altering the Activity of Cyclin E and Fas.

BACKGROUND/AIM: This study was designed to investigate the effect of IL-39 on T24 bladder cancer (BC) cell line survival and growth. MATERIALS AND METHODS: In order to assess the direct effect of IL-39 on survival, proliferation, and apoptosis of T24 BC cells, we utilized a clonogenic survival assay, a cell proliferation assay, and caspase-3 activity kits. Potential proliferative and apoptotic molecular mechanisms were evaluated by RT-PCR. RESULTS: Treatment of T24 BC cells with IL-39 resulted in a significant reduction in the percentage of colonies. The anti-tumor effect of IL-39 on T24 bladder cancer cells correlated strongly with a decrease in cyclin E, in combination with an increase in the mRNA levels of Fas. CONCLUSION: IL-39 impedes the growth and survival of T24 BC cells by inhibiting growth and promoting apoptosis. This ability to modulate gene transcription in neoplastic cells shows promise and warrants further research in immunotherapy.