scholarly journals Enhanced antineoplastic/therapeutic efficacy using 5-fluorouracil-loaded calcium phosphate nanoparticles

2018 ◽  
Vol 9 ◽  
pp. 2499-2515 ◽  
Author(s):  
Shanid Mohiyuddin ◽  
Saba Naqvi ◽  
Gopinath Packirisamy
Keyword(s):  
Electron Microscopy ◽  
Calcium Phosphate ◽  
Cancer Cells ◽  
Therapeutic Efficacy ◽  
Therapeutic Potential ◽  
Physicochemical Characterization ◽  
A549 Cells ◽  
Dependent Manner ◽  
Calcium Phosphate Nanoparticles ◽  
Apoptotic Induction

In the past few decades, the successful theranostic application of nanomaterials in drug delivery systems has significantly improved the antineoplastic potency of conventional anticancer therapy. Several mechanistic advantages of nanomaterials, such as enhanced permeability, retention, and low toxicity, as well as surface engineering with targeting moieties, can be used as a tool in enhancing the therapeutic efficacy of current approaches. Inorganic calcium phosphate nanoparticles have the potential to increase the therapeutic potential of antiproliferative drugs due to their excellent loading efficiency, biodegradable nature and controlled-release behaviour. Herein, we report a novel system of 5-fluorouracil (5-FU)-loaded calcium phosphate nanoparticles (CaP@5-FU NPs) synthesized via a reverse micelle method. The formation of monodispersed, spherical, crystalline nanoparticles with an approximate diameter of 160–180 nm was confirmed by different methods. The physicochemical characterization of the synthesized CaP@5-FU NPs was done with transmission electron microscopy (TEM), dynamic light scattering (DLS), field emission scanning electron microscopy (FE-SEM), Fourier-transform infrared spectroscopy (FTIR), and X-ray diffraction (XRD). The antineoplastic potential of the CaP@5-FU NPs against colorectal and lung cancer cells was reported. The CaP@5-FU NPs were found to inhibit half the population (IC50) of lung adenocarcinoma (A549) cells at 32 μg/mL and colorectal (HCT-15) cancer cells at 48.5 μg/mL treatment. The apoptotic induction of CaP@5-FU NPs was confirmed with acridine orange/ethidium bromide (AO/EB) staining and by examining the morphological changes with Hoechst and rhodamine B staining in a time-dependent manner. The apparent membrane bleb formation was observed in FE-SEM micrographs. The up-regulated proapoptotic and down-regulated antiapoptotic gene expressions were further confirmed with semiquantitative reverse transcriptase polymerase chain reaction (PCR). The increased intracellular reactive oxygen species (ROS) were quantified via flow cytometry upon CaP@5-FU NP treatment. Likewise, the cell cycle analysis was performed to confirm the enhanced apoptotic induction. Our study concludes that the calcium phosphate nanocarriers system, i.e. CaP@5-FU NPs, has higher antineoplastic potential as compared to 5-FU alone and can be used as an improved alternative to the antimitotic drug, which causes severe side effects when administrated alone.

Improved Therapeutic Efficacy of Topotecan Against A549 Lung Cancer Cells with Folate-targeted Topotecan Liposomes

2020 ◽  
Vol 21 (11) ◽  
pp. 902-909
Author(s):  
Jingxin Zhang ◽  
Weiyue Shi ◽  
Gangqiang Xue ◽  
Qiang Ma ◽  
Haixin Cui ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Drug Delivery ◽  
Cancer Cells ◽  
Targeted Delivery ◽  
Therapeutic Efficacy ◽  
Drug Delivery Systems ◽  
Lung Tumor ◽  
A549 Cells ◽  
Delivery Systems ◽  
Lung Cancer Cells

Background: Among all cancers, lung cancer has high mortality among patients in most of the countries in the world. Targeted delivery of anticancer drugs can significantly reduce the side effects and dramatically improve the effects of the treatment. Folate, a suitable ligand, can be modified to the surface of tumor-selective drug delivery systems because it can selectively bind to the folate receptor, which is highly expressed on the surface of lung tumor cells. Objective: This study aimed to construct a kind of folate-targeted topotecan liposomes for investigating their efficacy and mechanism of action in the treatment of lung cancer in preclinical models. Methods: We conjugated topotecan liposomes with folate, and the liposomes were characterized by particle size, entrapment efficiency, cytotoxicity to A549 cells and in vitro release profile. Technical evaluations were performed on lung cancer A549 cells and xenografted A549 cancer cells in female nude mice, and the pharmacokinetics of the drug were evaluated in female SD rats. Results: The folate-targeted topotecan liposomes were proven to show effectiveness in targeting lung tumors. The anti-tumor effects of these liposomes were demonstrated by the decreased tumor volume and improved therapeutic efficacy. The folate-targeted topotecan liposomes also lengthened the topotecan blood circulation time. Conclusion: The folate-targeted topotecan liposomes are effective drug delivery systems and can be easily modified with folate, enabling the targeted liposomes to deliver topotecan to lung cancer cells and kill them, which could be used as potential carriers for lung chemotherapy.

scholarly journals Staurosporine Induces the Generation of Polyploid Giant Cancer Cells in Non-Small-Cell Lung Carcinoma A549 Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Alexander Glassmann ◽  
Carmen Carrillo Garcia ◽  
Viktor Janzen ◽  
Dominik Kraus ◽  
Nadine Veit ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Lung Carcinoma ◽  
Small Cell Lung Carcinoma ◽  
A549 Cells ◽  
Small Cell ◽  
Dependent Manner ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma ◽  
Inhibition Of Proliferation ◽  
Polyploid Giant Cancer Cells

Cultivation of A549 non-small-cell lung carcinoma (NSCLC) cells in the presence of staurosporine (SSP) leads to a reduction or a lack of proliferation in a concentration-dependent manner. This inhibition of proliferation is accompanied by the generation of polyploid giant cancer cells (PGCCs) that are characterized by cell flattening, increased cell size, polyploidy, and polynucleation as determined by crystal violet staining, BrdU and DiI labelling, and flow cytometry as well as video time-lapse analysis. Continuous SSP treatment of A549 cells can preserve PGCCs for at least two months in a resting state. Upon removal of SSP, A549 PGCCs restart to divide and exhibit a proliferation pattern and cellular morphology indistinguishable from cells where PGCCs originally derived from. Thus, SSP-treated A549 cells represent a simple and reliable experimental model for the reversible generation of PGCCs and their subsequent experimental analysis.

scholarly journals Targeting Autophagy by MPT0L145, a Highly Potent PIK3C3 Inhibitor, Provides Synergistic Interaction to Targeted or Chemotherapeutic Agents in Cancer Cells

Cancers ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1345 ◽  
Author(s):  
Chun-Han Chen ◽  
Tsung-Han Hsieh ◽  
Yu-Chen Lin ◽  
Yun-Ru Liu ◽  
Jing-Ping Liou ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Drug Combination ◽  
Therapeutic Potential ◽  
Synthetic Lethality ◽  
Apoptotic Cell ◽  
A549 Cells ◽  
Growth Factor Receptor ◽  
Chemotherapeutic Agents ◽  
Autophagic Flux ◽  
Combination Strategies

Anticancer therapies reportedly promote pro-survival autophagy in cancer cells that confers drug resistance, rationalizing the concept to combine autophagy inhibitors to increase their therapeutic potential. We previously identified that MPT0L145 is a PIK3C3/FGFR inhibitor that not only increases autophagosome formation due to fibroblast growth factor receptor (FGFR) inhibition but also perturbs autophagic flux via PIK3C3 inhibition in bladder cancer cells harboring FGFR activation. In this study, we hypothesized that combined-use of MPT0L145 with agents that induce pro-survival autophagy may provide synthetic lethality in cancer cells without FGFR activation. The results showed that MPT0L145 synergistically sensitizes anticancer effects of gefitinib and gemcitabine in non-small cell lung cancer A549 cells and pancreatic cancer PANC-1 cells, respectively. Mechanistically, drug combination increased incomplete autophagy due to impaired PIK3C3 function by MPT0L145 as evidenced by p62 accumulation and no additional apoptotic cell death was observed. Meanwhile, drug combination perturbed survival pathways and increased vacuolization and ROS production in cancer cells. In conclusion, the data suggest that halting pro-survival autophagy by targeting PIK3C3 with MPT0L145 significantly sensitizes cancer cells to targeted or chemotherapeutic agents, fostering rational combination strategies for cancer therapy in the future.

scholarly journals Piperlongumine Induces Apoptosis and Synergizes with Cisplatin or Paclitaxel in Human Ovarian Cancer Cells

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Li-Hua Gong ◽  
Xiu-Xiu Chen ◽  
Huan Wang ◽  
Qi-Wei Jiang ◽  
Shi-Shi Pan ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Cell Apoptosis ◽  
Therapeutic Potential ◽  
Ovarian Cancer Cells ◽  
Human Ovarian Cancer ◽  
Dependent Manner ◽  
Ros Accumulation ◽  
M Phase ◽  
Natural Alkaloid

Piperlongumine (PL), a natural alkaloid fromPiper longum L., possesses the highly selective and effective anticancer property. However, the effect of PL on ovarian cancer cells is still unknown. In this study, we firstly demonstrate that PL selectively inhibited cell growth of human ovarian cancer cells. Furthermore, PL notably induced cell apoptosis, G2/M phase arrest, and accumulation of the intracellular reactive oxidative species (ROS) in a dose- and time-dependent manner. Pretreatment with antioxidant N-acety-L-cysteine could totally reverse the PL-induced ROS accumulation and cell apoptosis. In addition, low dose of PL/cisplatin or paclitaxel combination therapies had a synergistic antigrowth effect on human ovarian cancer cells. Collectively, our study provides new therapeutic potential of PL on human ovarian cancer.

scholarly journals Preparation of optimized lipid-coated calcium phosphate nanoparticles for enhanced in vitro gene delivery to breast cancer cells

2015 ◽  
Vol 3 (33) ◽  
pp. 6805-6812 ◽  
Author(s):  
Jie Tang ◽  
Li Li ◽  
Christopher B. Howard ◽  
Stephen M. Mahler ◽  
Leaf Huang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Calcium Phosphate ◽  
Cell Growth ◽  
Gene Delivery ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Cancer Cell Growth ◽  
Calcium Phosphate Nanoparticles ◽  
Transfection Agent

The optimized lipid coated calcium phosphate nanoparticles more efficiently deliver functional siRNA and inhibit the cancer cell growth, in comparison with the commercial transfection agent OligofactamineTM.

scholarly journals Phenethyl Isothiocyanate Induces Apoptosis Through ROS Generation and Caspase-3 Activation in Cervical Cancer Cells

2021 ◽  
Vol 12 ◽  
Author(s):  
Shoaib Shoaib ◽  
Saba Tufail ◽  
Mohammad Asif Sherwani ◽  
Nabiha Yusuf ◽  
Najmul Islam
Keyword(s):  
Cervical Cancer ◽  
Cancer Cells ◽  
Caspase 3 ◽  
Therapeutic Potential ◽  
Ros Generation ◽  
Main Concern ◽  
Therapeutic Effects ◽  
Dependent Manner ◽  
Phenethyl Isothiocyanate ◽  
Cervical Cancer Cells

The latest research shows that current chemotherapeutics are ineffective because of the development of resistance in cervical cancer cells, and hence, their scope of use is limited. The main concern of researchers at the moment is the discovery of safe and effective antiproliferative plant chemicals that can aid in the battle against cervical cancer. Previous studies have shown the possible anticancer potential of phenethyl isothiocyanate obtained from cruciferous plants for many cancers, which targets various signaling pathways to exercise chemopreventive and therapeutic effects. This provides the basis for studying phenethyl isothiocyanate's therapeutic potential against cervical cancer. In the present study, cervical cancer cells were treated with various doses of phenethyl isothiocyanate, alone and in combination with cisplatin. Phenethyl isothiocyanate alone was sufficient to cause nucleus condensation and fragmentation and induce apoptosis in cervical cancer cells, but evident synergistic effects were observed in combination with cisplatin. In addition, phenethyl isothiocyanate treatment increased the production of intracellular ROS in a dose-dependent manner in cervical cancer cells. Furthermore, investigation of phenethyl isothiocyanate induced mitochondrial reactive oxygen species production, and activation of caspases showed that phenethyl isothiocyanate significantly activated caspase-3.

scholarly journals Psiadin and plectranthone selectively inhibit colorectal carcinoma cells proliferation via modulating cyclins signaling and apoptotic pathways

PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0252820
Author(s):  
Khaled Y. Orabi ◽  
Mohamed S. Abaza ◽  
Yunus A. Luqmani ◽  
Rajaa Al-Attiyah
Keyword(s):  
Colorectal Carcinoma ◽  
Cancer Cells ◽  
Cell Lines ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Normal Breast ◽  
Dependent Manner ◽  
Isolation And Purification ◽  
Apoptotic Pathways ◽  
Dose Dependent

Three scarce terpenes, psiadin, plectranthone and saudinolide, were obtained after chromatographic isolation and purification from the aerial parts of the respective plants. Their identities were established based on their spectral data. Their anticancer effects against two human colorectal carcinoma cell lines, CCL233 and CCL235, along with the potential molecular mechanisms of action, were explored. Psiadin and plectranthone exhibited marked growth inhibition on both cell lines in a time- and dose-dependent manner with minimal cytotoxicity against normal breast cells (HB2). The terpenes even showed superior activities to the tested standards. Flow cytometry showed apoptosis induction and alteration in the cell cycle in colorectal cancer cells treated with both compounds. Nevertheless, it was also found that both compounds inhibited NF-κB transcriptional activity, induced mitochondrial membrane potential depolarization and increased the percentage of reactive oxygen species in the treated cancer cells in a dose-dependent manner as well. Since the anticancer effect of psiadin on cancer cells was higher than that produced by plectranthone, only psiadin was tested to determine its possible targets. The results suggested a high degree of specificity of action affecting particular cellular processes in both cancer cells. In conclusion, both terpenes, in particular psiadin, showed significant discriminative therapeutic potential between cancer and normal cells, a value that is missing in current chemotherapies.

scholarly journals MCP mediated active targeting calcium phosphate hybrid nanoparticles for the treatment of orthotopic drug-resistant colon cancer

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Shaobo Bai ◽  
Yang Sun ◽  
Ying Cheng ◽  
Weiliang Ye ◽  
Chenchao Jiang ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Calcium Phosphate ◽  
Protein Expression ◽  
Cancer Cells ◽  
Active Targeting ◽  
Cancer Targeting ◽  
Drug Resistant ◽  
Colon Cancer Cells ◽  
Apoptosis Pathway ◽  
Calcium Phosphate Nanoparticles

Abstract Background Colon cancer is a most common malignant cancer in digestive system, and it is prone to develop resistance to the commonly used chemotherapy drugs, leading to local recurrence and metastasis. Paris saponin VII (PSVII) could not only inhibit the proliferation of colon cancer cells but also effectively induce apoptosis of drug-resistant colon cancer cells and reduce the metastasis of drug-resistant colon cancer cells as well. However, PSVII was insoluble in water and fat. It displayed no selective distribution in body and could cause severe hemolysis. Herein, colon cancer targeting calcium phosphate nanoparticles were developed to carry PSVII to treat drug-resistant colon cancer. Results PSVII carboxymethyl-β-cyclodextrin inclusion compound was successfully encapsulated in colon cancer targeting calcium phosphate nanoparticles (PSVII@MCP-CaP) by using modified citrus pectin as stabilizer agent and colon cancer cell targeting moiety. PSVII@MCP-CaP significantly reduced the hemolysis of PSVII. Moreover, by specific accumulating in orthotopic drug-resistant colon cancer tissue, PSVII@MCP-CaP markedly inhibited the growth of orthotopic drug-resistant colon cancer in nude mice. PSVII@MCP-CaP promoted the apoptosis of drug-resistant colon cancer cells through mitochondria-mediated apoptosis pathway. Moreover, PSVII@MCP-CaP significantly inhibited the invasion and migration of drug-resistant colon cancer cells by increasing E-cadherin protein expression and reducing N-cadherin and MMP-9 protein expression. Conclusion PSVII@MCP-CaP has great potential in the treatment of drug-resistant colon cancer. This study also explores a new method to prepare active targeting calcium phosphate nanoparticles loaded with a fat and water insoluble compound in water. Graphical Abstract

Melatonin Enhances Anti-tumoral Effects of Menadione on Colon Cancer Cells

2021 ◽  
Vol 21 ◽  
Author(s):  
Alejandro Collin ◽  
Romina Kohan ◽  
Nori Tolosa de Talamoni ◽  
Gabriela Picotto
Keyword(s):  
Colon Cancer ◽  
Cell Migration ◽  
Cancer Cells ◽  
Nitrosative Stress ◽  
Therapeutic Potential ◽  
Cellular Growth ◽  
Dependent Manner ◽  
Colon Cancer Cells ◽  
Cancer Cell Growth ◽  
Oxidative And Nitrosative Stress

Background: Colon cancer is one of the most important causes of death in the entire world. New pharmacological strategies are always needed, especially in resistant variants of this pathology. We have previously reported that drugs such as menadione (MEN), D, L-buthionine-S,R-sulfoximine or calcitriol, used in combination, enhanced cell sensibility of breast and colon tumour models, due to their ability to modify the oxidative status of the cells. Melatonin (MEL), a hormone regulating circadian rhythms, has anti-oxidant and anti-apoptotic properties at low concentrations, while at high doses, it has been shown to inhibit cancer cell growth. Objective: The objective of this study is to determine the antitumoral action of the combination MEN and MEL on colon cancer cells. Methods: Caco-2 cells were employed to evaluate the effects of both compounds, used alone or combined, on cellular growth/morphology, oxidative and nitrosative stress, and cell migration. Results: MEN plus MEL dramatically reduced cell proliferation in a time and dose-dependent manner. The antiproliferative effects began at 48 h. At the same time, the combination modified the content of superoxide anion, induced the formation of reactive nitrogen species and enhanced catalase activity. Cell migration process was delayed. Also, changes in nuclear morphology consistent with cell death were observed. Conclusion: The enhanced effect of simultaneous use of MEN and MEL on Caco-2 cells suggests that this combined action may have therapeutic potential as an adjuvant on intestinal cancer acting in different oncogenic pathways.

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