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In the present study, we identified that two representative compounds (7 c and 9 f) of our newly synthesized coumarin-tagged bis-triazoles induced apoptosis in human pancreatic cells (PANC-1) by caspase 3/7mediated pathway. Both 7 c and 9 f (IC 50 =7.15±1.19 and 6.09±0.79 μM, respectively) were found to be ~100 times superior against PANC-1 as compared to the standard drug Gemcitabine (IC 50 =>500 μM), without showing any toxicity to the normal pancreatic epithelial cells (H6C7). Molecular docking studies further endorsed them as potential pancreatic cancer therapeutics due to their strong hydrogen bonding interactions with the epidermal growth factor receptor (EGFR) enzyme, which is overexpressed in cancerous cells including pancreatic cancer. Additionally, these compounds also showed moderate inhibitory activity against a panel of microbial strains. Overall, our findings reveal that the coumarin hybrids 7 c and 9 f are viable chemotypes to be adopted as templates for the development of new anticancer drugs, particularly against pancreatic cancer., (© 2024 The Author(s). ChemMedChem published by Wiley-VCH GmbH.)

Pancreatic cancer remains a formidable challenge in oncology due to its aggressive nature and limited treatment options. In this study, we investigate the potential therapeutic efficacy of elaiophylin, a novel compound, in targeting BxPC-3 and PANC-1 pancreatic cancer cells. We comprehensively explore elaiophylin's impact on apoptosis induction, proliferation inhibition, migration suppression, invasion attenuation, and angiogenesis inhibition, key processes contributing to cancer progression and metastasis. The results demonstrate that elaiophylin exerts potent pro-apoptotic effects, inducing a substantial increase in apoptotic cells. Additionally, elaiophylin significantly inhibits proliferation, migration, and invasion of BxPC-3 and PANC-1 cells. Furthermore, elaiophylin exhibits remarkable anti-angiogenic activity, effectively disrupting tube formation in HUVECs. Moreover, elaiophylin significantly inhibits the Wnt/β-Catenin signaling pathway. Our findings collectively demonstrate the multifaceted potential of elaiophylin as a promising therapeutic agent against pancreatic cancer via inhibition of the Wnt/β-Catenin signaling pathway. By targeting diverse cellular processes crucial for cancer progression, elaiophylin emerges as a prospective candidate for future targeted therapies. Further investigation of the in vivo efficacy of elaiophylin is warranted, potentially paving the way for novel and effective treatment approaches in pancreatic cancer management.

Background/aim: Acetyl-CoA carboxylase (ACC) is a rate-limiting enzyme in fatty acid synthesis. In this study, we investigated the effect of ACC inhibition on survival of pancreatic cancer cells., Material and Methods: AsPC-1, BxPC-3 and PANC-1 were used as human pancreatic cancer cell lines. 5-(etradecyloxy)-2-furoic acid (TOFA) and bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl) ethyl sulfide (BPTES) were used as inhibitors of ACC and glutaminase (GLS) respectively. Apoptotic and live cells were distinguished by annexin-V staining. The activity of caspase-3 was evaluated by measuring the fluorescence intensity of the degradation product of the substrate, N-acetyl-Asp-Glu-Val-Asp-7-amido-4-trifluoromethylcoumarin., Results: TOFA increased the number of annexin V-positive cells and enhanced caspase-3 activity in AsPC-1 and BxPC-3, but not in PANC-1 cells. The number of PANC-1 cells increased after 48 h in Earle's balanced salt solution. Interestingly, proliferation of PANC-1 cells was drastically suppressed by glutamine deprivation, but not by inhibition of glycolysis. BPTES also induced cell death to the same extent as glutamine deprivation. In addition, TOFA induced cell death of PANC-1 cells, both in the presence of BPTES and with glutamine deprivation, suggesting that inhibition of glutaminolysis causes cell death and enhances the effect of TOFA in PANC-1 cells., Conclusion: These findings suggest that glutaminolysis is important for the survival of pancreatic cancer cells showing tolerance to nutrient starvation such as PANC-1 cells, and use of a combination of inhibitors of ACC and GLS may be a new strategy for treatment of pancreatic cancer., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Pancreatic cancer is one of the most aggressive and lethal cancers, with poor prognosis and high resistance to current chemotherapeutic agents. Therefore, new therapeutic strategies and targets are underscored. Propolis has been reported to exhibit a broad spectrum of biological activities including anticancer activity., Objective: This study was carried out to assess the possible efficacy of Algerian propolis on the antitumor effect of doxorubicin on human pancreatic cancer cell line (PANC-1)., Methods: Modifications in cell viability, apoptosis and cell cycle progression, Pgp activity and intracellular accumulation of DOX were monitored to study the synergistic effect of Algerian propolis on the antitumor effects of DOX in PANC-1 cell line., Results: Both propolis and its combination with doxorubicin inhibited cell growth in a dose-dependent manner by inducing cell cycle arrest and apoptosis. In the presence of 100 μg/ml of propolis, the IC50 of DOX against PANC-1 cells decreased by 10.9-fold. Propolis combined with DOX increased after 48h, the number of cells in the G0G1 phase with dramatical increase in sub-G1 phase to reach 47% of total cells, corresponding to an increase of senescence or apoptotic state of the cells. Dead cell assay with annexinV/PI staining demonstrated that propolis and propolis-DOX treatment resulted in a remarkable induction of apoptosis as detected by flow cytometry. It was interesting to note that propolis at its 5IC50 was found as the most potent inducer of apoptosis. Our finding revealed that induced apoptosis in our conditions was caspase-3 and caspase-9 dependent. Flow cytometry showed that propolis increased the accumulation of doxorubicin within PANC-1 cells. Moreover, fluorescent intensity detection revealed that propolis remarkably increased the retention of rhodamine-123, 7- fold compared to 3-fold of verapamil, the most effective P-gp inhibitor., Conclusion: In conclusion, propolis sensitize pancreatic cancer cells to DOX via enhancing the intracellular retention of DOX due to blocking the efflux activity of P-gp pump, inducing cell cycle arrest and increasing apoptosis, finding that improuve the synergism of antitumor effect of Algerian propolis and DOX in pancreatic cancer cell line. Therefore, Algerian propolis may be an effective agent in a combined treatment with doxorubicin for increased therapeutic efficacy against pancreatic cancer., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Human pancreatic tumors are known to be highly resistant to nutrient starvation, and this prolongs their survival in the hypovascular (austere) tumor microenvironment. Agents that retard this tolerance to nutrient starvation represent a novel antiausterity strategy in anticancer drug discovery. (+)-Grandifloracin (GF), isolated from Uvaria dac, has shown preferential toxicity to PANC-1 human pancreatic cancer cells under nutrient starvation, with a PC50 value of 14.5 μM. However, the underlying mechanism is not clear. In this study, GF was found to preferentially induce PANC-1 cell death in a nutrient-deprived medium via hyperactivation of autophagy, as evidenced by a dramatic upregulation of microtubule-associated protein 1 light chain 3. No change was observed in expression of the caspase-3 and Bcl-2 apoptosis marker proteins. GF was also found to strongly inhibit the activation of Akt, a key regulator of cancer cell survival and proliferation. Because pancreatic tumors are highly resistant to current therapies that induce apoptosis, the alternative cell death mechanism exhibited by GF provides a novel therapeutic insight into antiausterity drug candidates.

Background: Gemcitabine is first-line therapy for advanced pancreatic ductal adenocarcinoma (PDAC) with a poor survival and response rate. Hyperbaric oxygenation (HBO) enhances delivery of oxygen to hypoxic tumor cells and increases their susceptibility to cytotoxic effects of chemotherapy. We hypothesized that the anticancer activity of gemcitabine (GEM) may be enhanced if tumor cells are placed in an oxygen-rich environment. The present study evaluated the effects of gemcitabine, HBO and their combination on apoptosis of tumor cells., Materials and Methods: PANC-1 and AsPc-1 PDAC tumor cell lines were used. Cultured tumor cells were treated with GEM at its growth-inhibitory concentration (IC50) and HBO at 2.5 ATA for 90 min or a combination of both (HBO then GEM and GEM then HBO). Twenty-four hours later, apoptotic cells in each group were analyzed and the apoptotic index (AI) was calculated., Results: PANC-1 cell line: HBO alone had no effect on AI: 6.5 ± 0.1 vs. 5.9 ± 0.1. HBO before and after gemcitabine did not further increase AI: 8.2 ± 0.1 (HBO-GEM), 8.5 ± 0.1 (GEM-HBO) vs. 8.1 ± 0.1 (GEM). The combination of HBO and gemcitabine significantly increased AI: 10.7 ± 0.02 (p<0.001 vs. all groups). AsPc-1 cell line: HBO-alone had no effect on AI: 5.9 ± 0.1 vs. 5.9 ± 0.1. HBO before and after gemcitabine did not further increase AI: 8.2 ± 0.1 (HBO-GEM), 8.4 ± 0.1 (GEM-HBO) vs. 8.0 ± 0.1 (GEM). The combination of HBO and gemcitabine significantly increased AI: 9.7 ± 0.1 (p<0.001 vs. all groups)., Conclusion: HBO-alone, whether administered before and after gemcitabine has no effect on apoptosis of PDAC cells in vitro. HBO significantly enhanced gemcitabine-induced apoptosis when administered during gemcitabine. Our findings suggest that the time window would be critical for using HBO as adjuvant to chemotherapy.

Isoalantolactone, a sesquiterpene lactone compound possesses antifungal, antibacteria, antihelminthic and antiproliferative activities. In the present study, we found that isoalantolactone inhibits growth and induces apoptosis in pancreatic cancer cells. Further mechanistic studies revealed that induction of apoptosis is associated with increased generation of reactive oxygen species, cardiolipin oxidation, reduced mitochondrial membrane potential, release of cytochrome c and cell cycle arrest at S phase. N-Acetyl Cysteine (NAC), a specific ROS inhibitor restored cell viability and completely blocked isoalantolactone-mediated apoptosis in PANC-1 cells indicating that ROS are involved in isoalantolactone-mediated apoptosis. Western blot study showed that isoalantolactone increased the expression of phosphorylated p38 MAPK, Bax, and cleaved caspase-3 and decreased the expression of Bcl-2 in a dose-dependent manner. No change in expression of phosphorylated p38 MAPK and Bax was found when cells were treated with isoalantolactone in the presence of NAC, indicating that activation of these proteins is directly dependent on ROS generation. The present study provides evidence for the first time that isoalantolactone induces ROS-dependent apoptosis through intrinsic pathway. Furthermore, our in vivo toxicity study demonstrated that isoalantolactone did not induce any acute or chronic toxicity in liver and kidneys of CD1 mice at dose of 100 mg/kg body weight. Therefore, isoalantolactone may be a safe chemotherapeutic candidate for the treatment of human pancreatic carcinoma.

Background: The ability to evade apoptosis is one of the key properties of cancer. The apoptogenic effect of nickel nanowires (Ni NWs) on cancer cell lines has never been adequately addressed. Due to the unique physicochemical characteristics of Ni NWs, we envision the development of a novel anticancer therapeutics specifically for pancreatic cancer. Thus, we investigated whether Ni NWs induce ROS-mediated apoptosis in human pancreatic adenocarcinoma (Panc-1) cells., Methods: In this study Ni NWs were fabricated using the electrodeposition method. Synthesized Ni NWs were physically characterized by energy dispersive X-ray analysis, UV-Vis spectroscopy of NanoDrop 2000 (UV-Vis), magnetization study, scanning electron microscopy, and transmission electron microscopy. Assessment of morphological apoptotic characteristics by phase contrast microscopy (PCM), Ni-NWs-induced apoptosis staining with ethidium bromide (EB) and acridine orange (AO) followed by fluorescence microscopy (FM) was performed. For molecular biological and biochemical characterization, Panc-1 cell culture and cytotoxic effect of Ni NWs were determined by using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay. Quantitative apoptosis was analyzed by flow cytometry staining with propidium iodide through cell cycle arrest and generation of ROS using 2', 7'-dichlorofluorescein diacetate fluorescence intensity. In all experiments, Panc-1 cancer cells without any treatment were used as the negative controls., Results: The intracellular uptake of Ni NWs through endocytosis by Panc-1 cells was observed by PCM. EB and AO staining of FM and MTT assay qualitatively and quantitatively confirmed the extent of apoptosis. Flow cytometric cell cycle arrest and ROS generation indicated Ni NWs as inducers of apoptotic cell death., Conclusion: We investigated the role of Ni NWs as inducers of ROS-mediated apoptosis in Panc-1 cells. These results suggested that Ni NWs could be an effective apoptotic agent for Panc-1 cells and have good potential for further research into a clinical treatment selective for pancreatic cancer.

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Pancreatic cancer is one of the most aggressive forms of cancer and is the seventh leading cause of cancer deaths worldwide. Pancreatic ductal adenocarcinoma (PDAC) accounts for over 90% of pancreatic cancers. Most pancreatic cancers are recalcitrant to radiation, chemotherapy, and immunotherapy, highlighting the urgent need for novel treatment options for this deadly disease. To this end, we screened a library of kinase inhibitors in the PDAC cell lines PANC-1 and BxPC-3 and identified two highly potent molecules: Aurora kinase inhibitor AT 9283 (AT) and EGFR kinase inhibitor WZ 3146 (WZ). Both AT and WZ exhibited a dose-dependent inhibition of viability in both cell lines. Thus, we conducted an in-depth multilevel (cellular, molecular, and proteomic) analysis with AT and WZ in PANC-1 cells, which harbor KRAS mutation and exhibit quasimesenchymal properties representing pancreatic cancer cells as having intrinsic chemoresistance and the potential for differential response to therapy. Elucidation of the molecular mechanism of action of AT and WZ revealed an impact on the programmed cell death pathway with an increase in apoptotic, multicaspase, and caspase 3/7 positive cells. Additionally, the key survival molecule Bcl-2 was impacted. Moreover, cell cycle arrest was observed with both kinase inhibitors. Additionally, an increase in superoxide radicals was observed in the AT-treated group. Importantly, proteomic profiling revealed differentially regulated key entities with multifaceted effects, which could have a deleterious impact on PDAC. These findings suggest potential targets for efficacious treatment, including a possible increase in the efficacy of immunotherapy using PD-L1 antibody due to the upregulation of lactoferrin and radixin. Furthermore, combination therapy outcomes with gemcitabine/platinum drugs may also be more effective due to an increase in the NADH dehydrogenase complex. Notably, protein–protein interaction analysis (STRING) revealed possible enrichment of reactome pathway entities. Additionally, novel therapy options, such as vimentin-antibody--drug conjugates, could be explored. Therefore, future studies with the two kinases as monotherapy/combination therapy are warranted. [ABSTRACT FROM AUTHOR]

Summary: This study aimed to evaluate the possible anticancer effects of two different pillar[5]arene derivatives (5Q-[P5] and 10Q-P[5]) on two different pancreatic cancer cell lines in vitro. For this purpose, changes in the expression of major genes that play a role in apoptosis and caspase pathways were investigated. Panc-1 and BxPC-3 cell lines were used in the study and the cytotoxic dose of pillar[5]arenes was determined by the MTT method. Changes in gene expression after pillar[5]arenes treatment were evaluated by real-time polymerase chain reaction (qPCR). Apoptosis was studied by flow cytometry. As a result of analysis, it was determined that proapoptotic genes and genes involved in major caspase activation were upregulated and antiapoptotic genes were down-regulated in Panc-1 cell line treated with pillar[5]arenes. Flow cytometric apoptosis analysis also showed an increased apoptosis rate in this cell line. On the contrary, although MTT analysis showed cytotoxic effect in BxPC-3 cell line treated with two pillar[5]arene derivatives, the apoptosis pathway was not active. This suggested that it may activate different death pathways for BxPC-3 cell line. Thus, it was first determined that the pillar[5]arene derivatives reduced cancer cell proliferation on pancreatic cancer cells. [ABSTRACT FROM AUTHOR]

Pancreatic cancer is one of the most aggressive forms of cancer and is the seventh leading cause of cancer deaths worldwide. Pancreatic ductal adenocarcinoma (PDAC) accounts for over 90% of pancreatic cancers. Most pancreatic cancers are recalcitrant to radiation, chemotherapy, and immunotherapy, highlighting the urgent need for novel treatment options for this deadly disease. To this end, we screened a library of kinase inhibitors in the PDAC cell lines PANC-1 and BxPC-3 and identified two highly potent molecules: Aurora kinase inhibitor AT 9283 (AT) and EGFR kinase inhibitor WZ 3146 (WZ). Both AT and WZ exhibited a dose-dependent inhibition of viability in both cell lines. Thus, we conducted an in-depth multilevel (cellular, molecular, and proteomic) analysis with AT and WZ in PANC-1 cells, which harbor KRAS mutation and exhibit quasimesenchymal properties representing pancreatic cancer cells as having intrinsic chemoresistance and the potential for differential response to therapy. Elucidation of the molecular mechanism of action of AT and WZ revealed an impact on the programmed cell death pathway with an increase in apoptotic, multicaspase, and caspase 3/7 positive cells. Additionally, the key survival molecule Bcl-2 was impacted. Moreover, cell cycle arrest was observed with both kinase inhibitors. Additionally, an increase in superoxide radicals was observed in the AT-treated group. Importantly, proteomic profiling revealed differentially regulated key entities with multifaceted effects, which could have a deleterious impact on PDAC. These findings suggest potential targets for efficacious treatment, including a possible increase in the efficacy of immunotherapy using PD-L1 antibody due to the upregulation of lactoferrin and radixin. Furthermore, combination therapy outcomes with gemcitabine/platinum drugs may also be more effective due to an increase in the NADH dehydrogenase complex. Notably, protein–protein interaction analysis (STRING) revealed possible enrichment of reactome pathway entities. Additionally, novel therapy options, such as vimentin-antibody--drug conjugates, could be explored. Therefore, future studies with the two kinases as monotherapy/combination therapy are warranted.

Objective: Delonix regia (L.) (Caesalpiniaceae) is one of the plants that have been used for centuries to prevent cancer. D. regia has been described as a strong anti-inflammatory, antibacterial, and analgesic. Also, the cytotoxicity of this plant has been proved due to its flavonoid compounds. Besides, silver (Ag) nanoparticles have been proved to be promising in cancer treatment. Methods: The synergistic effect of medicinal plant extracts with silver antibacterial nanoparticles on cancer cell inhibition was investigated. Cytotoxic effect of D. regia extract with silver NPs on MCF-7 and Panc-1 cancer cells was investigated by cell viability analysis, morphological changes, apoptosis induction, and TUNEL assay. Results: Results showed the cells treated with D. regia extract containing AgNPs exhibited a considerable reduction in viability percent in comparison with control cells. Analysis of MTT demonstrated that the IC50 value of D. regia extract and AgNPs on both cell lines observed in 0.5 mg/mL for 24 h. The results demonstrated that the maximum inhibition of both cell lines growth was observed in 1.5 mg/L and 0.2 mg/L in the presence with D. regia and AgNPs, respectively. Also, morphological characteristics of cells indicated that D. regia extract and silver NPs induce cell death by apoptosis and it is confirmed by TUNEL assay. Conclusion: Interestingly, D. regia extract and Ag NPs had no significant cytotoxicity against normal cells. It can be concluded that Delonix regia plant and silver nanoparticles have an inhibitory potential on two cancer cell lines, but in the use of synergism of D. regia extract and AgNPs, the induction of apoptosis in MCF-7 and Panc-1 was increased. Interestingly, in normal cells, no significant negative effect was observed as control. [ABSTRACT FROM AUTHOR]

Objective(s): Pyocyanin, a blue-green pigment produced by Pseudomonas aeruginosa, interferes with host redox cycles, which can lead to generation of reactive oxygen species and progressive cellular oxidative damage. The aim of this study was to assess the influence of pyocyanin on human pancreatic cancer cell line.Materials and Methods: Polymerase Chain Reaction (PCR) was applied to confirm the existence of a specific pyocyanin producing gene (phzM). The pigment was then characterized by UV-visible, FT-IR, and HPLC analysis. Panc-1 cells were treated by different concentrations of pyocyanin and their cytotoxic effect as well as the induction of apoptosis/necrosis were evaluated by XTT assay and flow cytometry.Results: An overnight pyocyanin treatment resulted in significant cell reduction in a concentration-dependent manner. Inhibition rate of 6 mg.ml-1 pyocyanin (the highest concentration) extracted from clinical and soil isolates of P. aeruginosa were 98.69±0.23 and 89.88±1.86%, respectively, which decreased as the pyocyanin concentration lessened. Pyocyanin could also induce dose-dependent apoptosis/necrosis in Panc-1 cells after 24 hr.Conclusion: We reported, for the first time, cytotoxic effects of pyocyanin against human pancreatic cancer cell line. Considering this effect of the pigment, study on pyocyanin as a potential anti-tumor biodrug requires further studies.

Cephalosporium curvulum lectin (CSL), a lectin from pathogenic fungus has exquisite specificity towards α1–6 linkage of core fucosylated glycans, expressed in hepatocellular and pancreatic cancer. Interaction and effect of CSL and other fucose specific lectins LCA and AOL on HepG2 and PANC-1 cells was investigated. CSL, LCA and AOL exhibited strong binding to PANC-1 cells which could be effectively blocked by competing glycoprotein mucin. Effect of CSL, LCA and AOL on PANC-1 and HepG2 cells was determined by MTT assay and all the three lectins inhibited the cell growth which could be blocked by mucin, cell cycle analysis revealed that CSL increased hypodiploid HepG2 cell population indicating cellular apoptosis. CSL induced apoptosis in HepG2 cells was confirmed by Annexin V/PI assay. CSL induced increase in early apoptotic HepG2 cell population, a time dependent increase in the expression of caspases-3, 9 and cytochrome-c was observed by western blotting suggesting the possible involvement of intrinsic caspase dependent apoptosis. Increase in ROS and decrease in MMP demonstrated involvement of intrinsic caspase dependent apoptosis. Quantification of AFP in HCC patients using CSL lectin-antibody sandwich ELISA, supports diagnostic potential of CSL. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To s tudy t he influences of metformin on the proliferation and apoptosis of pancreatic cancer cells and its dose-effect relationship and crucial molecular mechanism. MATERIALS AND METHODS: With human pancreatic cancer cell line PANC-1 as the study object, different concentrations of metformin were added for intervention. Then, the proliferation of PANC-1 cells was detected via methyl thiazolyl tetrazolium (MTT) assay to determine the dose-effect relationship of metformin in PANC-1 cell proliferation. PANC-1 cells were treated with metformin at three appropriate concentrations as Metformin treatment groups, and an equal amount of dimethyl sulfoxide (DMSO) was added in Control group. Flow cytometry was performed to detect PANC-1 cell cycle and apoptosis, and the apoptosis of PANC-1 cells was also evaluated via terminal deoxynucleotidyl transferase- mediated dUTP nick end labeling (TUNEL) assay. Caspase-3 protein localization and expression in PANC-1 cells were detected using immunofluorescence assay. Besides, the expressions of the apoptosis-associated proteins Caspase-3, B-cell lymphoma 2 (Bcl-2), and Bcl-2 associated X protein (Bax) and phosphatidylinositol 3-hydroxy kinase (PI3K), phosphorylated protein kinase B (p-Akt), and p-mammalian target of rapamycin (mTOR) proteins related to the mTOR pathway were detected using Western blotting. RESULTS: Metformin repressed the proliferation of human pancreatic cancer PANC-1 cells in a concentration-dependent and time-dependent manner. Compared with Control group, Metformin treatment groups (0, 20 and 40 mM) exhibited a higher proportion of PANC-1 cells in G0/G1 phases, and a lower proportion of PANC-1 cells in S phase (p<0.05), and the change in the proportion of cells in G2/M phase was not statistically significant (p>0.05). Moreover, Metformin treatment groups (0, 20, and 40 mM) had more apoptotic PANC-1 cells, higher expression levels of pro-apoptosis proteins Caspase-3 and Bax and lower expression levels of anti-apoptosis protein Bcl-2 and the mTOR pathway-related proteins PI3K, p-Akt, and p-mTOR in cells than Control group (p<0.05). CONCLUSIONS: Metformin modulates the mTOR signaling pathway to reduce the proliferation of pancreatic cancer cell, but increase their apoptosis. [ABSTRACT FROM AUTHOR]

Objective: The effect of Polygonum cuspidatum extract on Pancreatic cancer cell line Panc-1 was investigated by extracting Polygonum cuspidatum extracts into human pancreatic cancer cell proliferation and apoptosis phenotype. Methods: Different concentrations(0, 10, 50, 100, 150, 200 μg/m L) of Polygonum cuspidatum extract were prepared, and each concentration of Polygonum cuspidatum extract was added to the human pancreatic cancer Panc-1 cell line to be treated for 24 h. The proliferation activity of the cell line Panc-1 was detected by CCK-8(cell counting kit-8) method; the human pancreatic cancer cell line Panc-1 was treated with 100 μg/m L Polygonum cuspidatum extract for 24 h, and then flow cytometry was used( FCM) was used to detect the cell cycle and apoptosis distribution; 100 μg/m L Polygonum cuspidatum extract was used to treat human pancreatic cancer cell line Panc-1 for 24 h, and the total RNA and total protein were extracted. Subsequent real-time PCR and Western blot were used to detect human pancreatic cancer.Transcription and translation levels of the cell line Panc-1 proliferation marker genes PCNA, CDK2 and apoptosis marker genes BAD,BAX. Results: The results of CCK-8 showed that the inhibition rate of Polygonum cuspidatum extract on the proliferation of human pancreatic cancer cell line Panc-1 increased with concentration. The results of flow cytometry showed that Polygonum cuspidatum extract inhibited the proliferation of human pancreatic cancer cells and promoted its apoptosis. The results of real-time PCR and Western blot showed The extract of Polygonum cuspidatum can decrease the expression of PCNA and CDK2 in human pancreatic cancer cell proliferation, and the expression of apoptosis marker gene BAD and BAX increased. Conclusion: Polygonum cuspidatum extract can inhibit the proliferation and promote apoptosis of human pancreatic cancer cell line Panc-1 [ABSTRACT FROM AUTHOR]

Objective(s): Pyocyanin, a blue-green pigment produced by Pseudomonas aeruginosa, interferes with host redox cycles, which can lead to generation of reactive oxygen species and progressive cellular oxidative damage. The aim of this study was to assess the influence of pyocyanin on human pancreatic cancer cell line. Materials and Methods: Polymerase Chain Reaction (PCR) was applied to confirm the existence of a specific pyocyanin producing gene (phzM). The pigment was then characterized by UV-visible, FTIR, and HPLC analysis. Panc-1 cells were treated by different concentrations of pyocyanin and their cytotoxic effect as well as the induction of apoptosis/necrosis were evaluated by XTT assay and flow cytometry. Results: An overnight pyocyanin treatment resulted in significant cell reduction in a concentrationdependent manner. Inhibition rate of 6 mg.ml-1 pyocyanin (the highest concentration) extracted from clinical and soil isolates of P. aeruginosa were 98.69±0.23 and 89.88±1.86%, respectively, which decreased as the pyocyanin concentration lessened. Pyocyanin could also induce dose-dependent apoptosis/necrosis in Panc-1 cells after 24 hr. Conclusion: We reported, for the first time, cytotoxic effects of pyocyanin against human pancreatic cancer cell line. Considering this effect of the pigment, study on pyocyanin as a potential anti-tumor biodrug requires further studies. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinomas are an extremely aggressive and devastating type of cancer with high mortality. Given the dense stroma and poor vascularization, accessibility to nutrients is limited in the tumor microenvironment. Here, we aimed to elucidate the role of autophagy in promoting the survival of human pancreatic cancer PANC-1 cells exposed to nutrient-deprived media (NDM) lacking glucose, amino acids, and serum. NDM inhibited Akt activity and phosphorylation of p70 S6K, and induced AMPK activation and mitochondrial depolarization. NDM also time-dependently increased LC3-II accumulation, number of GFP-LC3 puncta, and colocalization between GFP-LC3 and lysosomes. These results suggested that autophagy was progressively activated through Akt- and AMPK-mTOR pathway in nutrient-deficient PANC-1 cells. Autophagy inhibitors (chloroquine and wortmannin) or silencing of Atg5 augmented PANC-1 cell death in NDM. In cells exposed to NDM, chloroquine and wortmannin induced apoptosis and Z-VAD-fmk inhibited cytotoxicity of these inhibitors. These data demonstrate that autophagy is anti-apoptotic and sustains the survival of PANC-1 cells following extreme nutrient deprivation. Autophagy modulation may be a viable therapeutic option for cancer cells located in the core of solid tumors with a nutrient-deficient microenvironment. [ABSTRACT FROM AUTHOR]

A series of isoprenylated coumarins has been designed, synthesized, and evaluated against human pancreatic adenocarcinoma cell line PANC-1 under nutrient-rich and nutrient-deprived conditions. The compounds described investigate the effect of isoprenyl chain length and positioning on cell growth inhibition. The majority of these compounds displayed cytotoxicity against PANC-1 cells selectively in the absence of essential amino acids, glucose, and serum, and showed no cytotoxicity under nutrient-rich conditions. In this study, compound 6 exhibited the highest cytotoxic activity with an LC 50 value of 4 μM and induced apoptosis-like morphological changes in PANC-1 cells after a 24-h incubation. The evaluated structure–activity relationships show that substitution at the 6-position and the presence of a farnesyl isoprenyl tail are important structural features for enhanced preferential cytotoxicity. These findings provide important information to designing other structural analogues for potential application as novel pancreatic antitumor agents. [ABSTRACT FROM AUTHOR]

Pancreatic cancer is a devastating disease characterized by low sensitivity to conventional chemotherapeutic treatment that has a poor prognosis. Therefore, novel effective chemotherapeutic regimens need to be developed. In this study, we analyzed the combined cytotoxic effect of triptolide and hydroxycamptothecin (HCPT) on pancreatic cancer cell line PANC-1 by using 3-(4.5-dimethylthiazol-2-yl)-5-(3-carboxy-methoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) and fluorescence- activated cell sorting (FACS) assays. Our results showed that the sensitivity of a combined therapy using triptolide and HCPT was higher than that of triptolide or HCPT alone and that activation of caspase-9/caspase-3 and inhibition of nuclear factor-kappaB (NF-κB) signaling pathway may contribute to the synergistic cytotoxic effect of this combination therapy. Therefore, our observations provided evidence supporting the clinical applications of the combination chemotherapy using triptolide and HCPT for treating pancreatic cancer. [ABSTRACT FROM AUTHOR]

Pancreatic cancer has been a serious disease worldwide for its high mortality. Cucurbitacin E is a member of triterpenoid family isolated from plants showing antiproliferative activity on various cancer cells. In this study, we have explored whether cucurbitacin E also has an anti-tumor effect on pancreatic cancer cells. Human pancreatic cancer cells PANC-1 were used to explore the effect and possible mechanisms of cucurbitacin E on cell cycle progression, apoptosis and proliferation. Cucurbitacin E has inhibited the growth of PANC-1 cells in a dose- and time-dependent manner, and has caused accumulation of cells at the G2/M phase as well as apoptosis. Western blotting also showed that cucurbitacin E treatment can inhibit STAT3 phosphorylation while upregulate p53 expression. Our results suggested that cucurbitacin E may be an effective regimen for the chemotherapy of pancreatic cancer. [ABSTRACT FROM AUTHOR]