In vitro evaluation of cytotoxic and apoptotic activities of ethanolic extract of sweet apricot kernel on PANC-1 pancreatic cancer cells

2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Fatemeh Aamazadeh ◽  
Jaleh Barar ◽  
Yalda Rahbar Saadat ◽  
Alireza Ostadrahimi
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Real Time ◽  
Ethanolic Extract ◽  
B Cell Lymphoma ◽  
Normal Cells ◽  
Content Type ◽  
Apricot Kernel ◽  
Pancreatic Cancer Cells ◽  
Apoptotic Effects

Purpose This study aimed to evaluate the cytotoxic/apoptotic effects of sweet apricot kernel ethanolic extract (SAEE) on human cancerous PANC-1 and 293/KDR normal cells. Design/methodology/approach The extract was prepared by maceration, and its chemical composition was analyzed by gas chromatography-mass spectrometry (GC-MS). The biological effects of SAEE on PANC-1 and 293/KDR cells were investigated using MTT (3–(4, 5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromide) assay, DAPI (4',6-diamidino-2-phenylindole) and AnnexinV/propidium iodide (PI) staining. The expression of pro- and anti-apoptotic genes was evaluated by real-time quantitative polymerase chain reaction (real-time q-PCR) analysis. Findings The SAEE showed the selective growth inhibitory activity against PANC-1 cells with an IC50 (the 50% inhibitory concentration) value of about 1 mg/mL at 72 h. Further investigations by DAPI staining and flow cytometry revealed nucleus fragmentation and elevation of apoptotic cells, respectively. Also, a significant decrease in B-cell lymphoma 2 (Bcl-2)/Bcl-2-associated x protein (Bax) ratio (0.41, p = 0.001) and the up-regulation of caspase-3 expression (1.5 fold, p = 0.002) indicated the induction of apoptosis in PANC-1 cells but not in 293/KDR non-cancerous cells. These results suggest that SAEE could induce apoptosis in cancer cells via a mitochondrial dependent pathway. Furthermore, GC-MS analysis showed that the SAEE is rich in γ-sitosterol and γ-tocopherol. Overall, the findings suggest that because of the selective impacts of SAEE on PANC-1 cells, it can be considered as a supportive care in adjuvant therapy for pancreatic cancer. However, the potent anticancer effects of main components of SAEE and its clinical value as an antitumor drug should be further investigated. Research limitations/implications Considerable limitations of this study were that the related mechanisms of selective impacts of SAEE on cancerous and normal cells and potent cytotoxic/apoptotic effects of γ-sitosterol and γ-tocopherol as major components of SAEE were not investigated. Originality/value Recently, a growing interest has been dedicated to plant-based natural products. Sweet apricot kernel exerts a number of pharmacological activities; however, the anticancer effect, related mechanisms and its active compounds were rarely investigated. In this study, the authors aimed to evaluate the cytotoxic/apoptotic effects of SAEE on human cancerous PANC-1 and 293/KDR normal cells.

scholarly journals Catalase Modulates the Radio-Sensitization of Pancreatic Cancer Cells by Pharmacological Ascorbate

Antioxidants ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 614
Author(s):  
Juan Du ◽  
Rory S. Carroll ◽  
Garett J. Steers ◽  
Brett A. Wagner ◽  
Brianne R. O’Leary ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Standard Of Care ◽  
Related Factor ◽  
Dual Roles ◽  
Normal Cells ◽  
Pancreatic Cancer Cells ◽  
Radiation Induced ◽  
Long Term Survivors

Pancreatic cancer cells (PDACs) are more susceptible to an oxidative insult than normal cells, resulting in greater cytotoxicity upon exposure to agents that increase pro-oxidant levels. Pharmacological ascorbate (P-AscH−), i.e., large amounts given intravenously (IV), generates significant fluxes of hydrogen peroxide (H2O2), resulting in the killing of PDACs but not normal cells. Recent studies have demonstrated that P-AscH− radio-sensitizes PDAC but is a radioprotector to normal cells and tissues. Several mechanisms have been hypothesized to explain the dual roles of P-AscH− in radiation-induced toxicity including the activation of nuclear factor-erythroid 2-related factor 2 (Nrf2), RelB, as well as changes in bioenergetic profiles. We have found that P-AscH− in conjunction with radiation increases Nrf2 in both cancer cells and normal cells. Although P-AscH− with radiation decreases RelB in cancer cells vs. normal cells, the knockout of RelB does not radio-sensitize PDACs. Cellular bioenergetic profiles demonstrate that P-AscH− with radiation increases the ATP demand/production rate (glycolytic and oxidative phosphorylation) in both PDACs and normal cells. Knocking out catalase results in P-AscH− radio-sensitization in PDACs. In a phase I trial where P-AscH− was included as an adjuvant to the standard of care, short-term survivors had higher catalase levels in tumor tissue, compared to long-term survivors. These data suggest that P-AscH− radio-sensitizes PDACs through increased peroxide flux. Catalase levels could be a possible indicator for how tumors will respond to P-AscH−.

scholarly journals Investigation of Dextran-Coated Superparamagnetic Nanoparticles for Targeted Vinblastine Controlled Release, Delivery, Apoptosis Induction, and Gene Expression in Pancreatic Cancer Cells

Molecules ◽  
2020 ◽  
Vol 25 (20) ◽  
pp. 4721 ◽  
Author(s):  
Salim Albukhaty ◽  
Sharafaldin Al-Musawi ◽  
Salih Abdul Mahdi ◽  
Ghassan M. Sulaiman ◽  
Mona S. Alwahibi ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Pancreatic Cancer ◽  
Transmission Electron Microscopy ◽  
Cancer Cells ◽  
Real Time ◽  
Superparamagnetic Nanoparticles ◽  
Apoptosis Induction ◽  
Pancreatic Cancer Cells ◽  
Transmission Electron ◽  
Biological Studies

In the current study, the surface of superparamagnetic iron oxide (SPION) was coated with dextran (DEX), and conjugated with folic acid (FA), to enhance the targeted delivery and uptake of vinblastine (VBL) in PANC-1 pancreatic cancer cells. Numerous analyses were performed to validate the prepared FA-DEX-VBL-SPION, such as field emission scanning transmission electron microscopy, high-resolution transmission electron microscopy, dynamic light scattering (DLS), Zeta Potential, Fourier transform infrared spectroscopy, and vibrating sample magnetometry (VSM). The delivery system capacity was evaluated by loading and release experiments. Moreover, in vitro biological studies, including a cytotoxicity study, cellular uptake assessment, apoptosis analysis, and real-time PCR, were carried out. The results revealed that the obtained nanocarrier was spherical with a suitable dispersion and without visible aggregation. Its average size, polydispersity, and zeta were 74 ± 13 nm, 0.080, and −45 mV, respectively. This dual functional nanocarrier also exhibited low cytotoxicity and a high apoptosis induction potential for successful VBL co-delivery. Real-time quantitative PCR analysis demonstrated the activation of caspase-3, NF-1, PDL-1, and H-ras inhibition, in PANC-1 cells treated with the FA-VBL-DEX-SPION nanostructure. Close inspection of the obtained data proved that the FA-VBL-DEX-SPION nanostructure possesses a noteworthy chemo-preventive effect on pancreatic cancer cells through the inhibition of cell proliferation and induction of apoptosis.

Photothermal detection of nicotine-induced apoptotic effects in pancreatic cancer cells

Life Sciences ◽  
2004 ◽  
Vol 75 (22) ◽  
pp. 2677-2687 ◽  
Author(s):  
Valentin Galitovsky ◽  
Parimal Chowdhury ◽  
Vladimir P. Zharov
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Pancreatic Cancer Cells ◽  
Apoptotic Effects

scholarly journals Zoledronic acid induces antiproliferative and apoptotic effects in human pancreatic cancer cells in vitro

2003 ◽  
Vol 88 (12) ◽  
pp. 1971-1978 ◽  
Author(s):  
P Tassone ◽  
P Tagliaferri ◽  
C Viscomi ◽  
C Palmieri ◽  
M Caraglia ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Zoledronic Acid ◽  
Cancer Cells ◽  
Human Pancreatic Cancer ◽  
Pancreatic Cancer Cells ◽  
Apoptotic Effects

scholarly journals TEOA Promotes Autophagic Cell Death via ROS-Mediated Inhibition of mTOR/p70S6k Signaling Pathway in Pancreatic Cancer Cells

2021 ◽  
Vol 9 ◽  
Author(s):  
Chen Yang ◽  
Yanchun Li ◽  
Wanye Hu ◽  
Xu Wang ◽  
Jiayu Hu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Death ◽  
Mitochondrial Dysfunction ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
B Cell Lymphoma ◽  
Autophagic Cell Death ◽  
Autophagic Flux ◽  
Dependent Manner ◽  
Pancreatic Cancer Cells

Pancreatic cancer is a common malignant tumor with high mortality, and novel therapeutic options have focused on ameliorating its poor prognosis. TEOA, a traditional Chinese herbal medicine, exhibits anti-inflammatory and anti-cancer activities. Our recent study has shown that TEOA inhibits proliferation and induces DNA damage in diffuse large B-cell lymphoma cells by activating the ROS-mediated p38 MAPK pathway. However, its effects on pancreatic cancer cells remain unknown. In the present study, we evaluated the effects of TEOA on the proliferation, migration of pancreatic cancer cells and explored the possible underlying mechanism of action. We found that TEOA significantly inhibited the proliferation and migration of pancreatic cancer cells in a time- and dose-dependent manner. Mechanistically, TEOA significantly induced mitochondrial dysfunction in PANC1 and SW1990 cells, as evidenced by the collapse of the mitochondrial membrane potential, exhausted ATP level, and excessive accumulation of intracellular ROS. Notably, our further experiments showed that TEOA induced autophagic cell death in pancreatic ductal adenocarcinoma cells by inactivating the ROS-dependent mTOR/p70S6k signaling pathway. More importantly, both pharmacological or genetic blocking of the autophagic flux signal could partly restore the cytotoxicity of TEOA, whereas activation of autophagy by rapamycin or EBSS induced starvation facilitated the cytotoxicity of TEOA. Concomitantly, N-acetylcysteine, a ROS scavenger, abolished the inhibition of the mTOR signaling pathway, thus preventing autophagy and restoring cell viability. Taken together, our results reveal that TEOA can lead to ROS-dependent autophagic cell death of pancreatic cancer cells by inducing mitochondrial dysfunction, which might be a promising therapeutic agent for pancreatic cancer.

scholarly journals Designing Protease Sensors for Real-Time Imaging of Trypsin Activation in Pancreatic Cancer Cells†

Biochemistry ◽  
2009 ◽  
Vol 48 (15) ◽  
pp. 3519-3526 ◽  
Author(s):  
Ning Chen ◽  
Jin Zou ◽  
Siming Wang ◽  
Yiming Ye ◽  
Yun Huang ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Real Time ◽  
Real Time Imaging ◽  
Pancreatic Cancer Cells

scholarly journals Role of Peroxisome Proliferator-Activated Receptorβ/δand B-Cell Lymphoma-6 in Regulation of Genes Involved in Metastasis and Migration in Pancreatic Cancer Cells

PPAR Research ◽  
2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Jeffrey D. Coleman ◽  
Jerry T. Thompson ◽  
Russell W. Smith ◽  
Bogdan Prokopczyk ◽  
John P. Vanden Heuvel
Keyword(s):  
Pancreatic Cancer ◽  
Basement Membrane ◽  
Cancer Cells ◽  
Target Genes ◽  
B Cell Lymphoma ◽  
Human Pancreatic Cancer ◽  
Cancer Tissue ◽  
Peroxisome Proliferator ◽  
Matrix Remodeling ◽  
Pancreatic Cancer Cells

PPARβ/δis a ligand-activated transcription factor that regulates various cellular functions via induction of target genes directly or in concert with its associated transcriptional repressor,BCL-6. Matrix remodeling proteinases are frequently over-expressed in pancreatic cancer and are involved with metastasis. The present study tested the hypothesis thatPPARβ/δis expressed in human pancreatic cancer cells and that its activation could regulateMMP-9, decreasing cancer cells ability to transverse the basement membrane. In human pancreatic cancer tissue there was significantly higher expression ofMMP-9andPPARβ/δ, and lower levels ofBCL-6mRNA.PPARβ/δactivation reduced the TNFα-induced expression of various genes implicated in metastasis and reduced the invasion through a basement membrane in cell culture models. Through the use of short hairpin RNA inhibitors ofPPARβ/δ,BCL-6, andMMP-9, it was evident thatPPARβ/δwas responsible for the ligand-dependent effects whereasBCL-6dissociation upon GW501516 treatment was ultimately responsible for decreasingMMP-9expression and hence invasion activity. These results suggest thatPPARβ/δplays a role in regulating pancreatic cancer cell invasion through regulation of genes via ligand-dependent release ofBCL-6and that activation of the receptor may provide an alternative therapeutic method for controlling migration and metastasis.

Sign in / Sign up

Export Citation Format

Share Document