scholarly journals 9-O-Terpenyl-Substituted Berberrubine Derivatives Suppress Tumor Migration and Increase Anti-Human Non-Small-Cell Lung Cancer Activity

2021 ◽  
Vol 22 (18) ◽  
pp. 9864
Author(s):  
Jia-Ming Chang ◽  
Jin-Yi Wu ◽  
Shu-Hsin Chen ◽  
Wen-Ying Chao ◽  
Hsiang-Hao Chuang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Clinical Intervention ◽  
Antitumor Agent ◽  
Chemotherapeutic Agents ◽  
Small Cell ◽  
Autophagic Flux ◽  
Small Cell Lung

Lung cancer is one of the most common cancers and the leading cause of death in humans worldwide. Non-small-cell lung cancer (NSCLC) accounts for approximately 85% of lung cancer cases and is often diagnosed at a late stage. Among patients with NSCLC, 50% die within 1 year after diagnosis. Even with clinical intervention, the 5-year survival rate is only approximately 20%. Therefore, the development of an advanced therapeutic strategy or novel agent is urgently required for treating NSCLC. Berberine exerts therapeutic activity toward NSCLC; therefore, its activity as an antitumor agent needs to be explored further. In this study, three terpenylated-bromide derivatives of berberrubine were synthesized and their anti-NSCLC activities were evaluated. Each derivative had higher anti-NSCLCs activity than berberrubine and berberine. Among them, 9-O-gernylberberrubine bromide (B4) and 9-O-farnesylberberrubine bromide (B5) showed greater growth inhibition, cell-cycle regulation, in vitro tumorigenesis suppression, and tumor migration reduction. In addition, some degree of apoptosis and autophagic flux blocking was noted in the cells under B4 and B5 treatments. Our study demonstrates that the berberrubine derivatives, B4 and B5, exhibit impressive anti-NSCLC activities and have potential for use as chemotherapeutic agents against NSCLC.

scholarly journals Co-Loaded Curcumin and Methotrexate Nanocapsules Enhance Cytotoxicity against Non-Small-Cell Lung Cancer Cells

Molecules ◽  
2020 ◽  
Vol 25 (8) ◽  
pp. 1913
Author(s):  
Loanda Aparecida Cabral Rudnik ◽  
Paulo Vitor Farago ◽  
Jane Manfron Budel ◽  
Amanda Lyra ◽  
Fernanda Malaquias Barboza ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Drug Release ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Colloidal Suspensions ◽  
Chemotherapeutic Agents ◽  
Small Cell ◽  
Spherical Particles ◽  
Small Cell Lung

Background: As part of the efforts to find natural alternatives for cancer treatment and to overcome the barriers of cellular resistance to chemotherapeutic agents, polymeric nanocapsules containing curcumin and/or methotrexate were prepared by an interfacial deposition of preformed polymer method. Methods: Physicochemical properties, drug release experiments and in vitro cytotoxicity of these nanocapsules were performed against the Calu-3 lung cancer cell line. Results: The colloidal suspensions of nanocapsules showed suitable size (287 to 325 nm), negative charge (−33 to −41 mV) and high encapsulation efficiency (82.4 to 99.4%). Spherical particles at nanoscale dimensions were observed by scanning electron microscopy. X-ray diffraction analysis indicated that nanocapsules exhibited a non-crystalline pattern with a remarkable decrease of crystalline peaks of the raw materials. Fourier-transform infrared spectra demonstrated no chemical bond between the drug(s) and polymers. Drug release experiments evidenced a controlled release pattern with no burst effect for nanocapsules containing curcumin and/or methotrexate. The nanoformulation containing curcumin and methotrexate (NCUR/MTX-2) statistically decreased the cell viability of Calu-3. The fluorescence and morphological analyses presented a predominance of early apoptosis and late apoptosis as the main death mechanisms for Calu-3. Conclusions: Curcumin and methotrexate co-loaded nanocapsules can be further used as a novel therapeutic strategy for treating non-small-cell lung cancer.

scholarly journals Berberine Derivatives Suppress Cellular Proliferation and Tumorigenesis In Vitro in Human Non-Small-Cell Lung Cancer Cells

2020 ◽  
Vol 21 (12) ◽  
pp. 4218
Author(s):  
Jia-Ming Chang ◽  
Kam-Hong Kam ◽  
Wen-Ying Chao ◽  
Pei-Wen Zhao ◽  
Shu-Hsin Chen ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Survival Rate ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Therapeutic Agent ◽  
Small Cell ◽  
Autophagic Flux ◽  
Small Cell Lung ◽  
Berberine Derivatives

Lung cancer is the leading cause of death in the world, and the most common type of lung cancer is non-small-cell lung cancer (NSCLC), accounting for 85% of lung cancer. Patients with NSCLC, when detected, are mostly in a metastatic stage, and over half of patients diagnosed with NSCLC die within one year after diagnosis; the 5-year survival rate is 24%. However, in patients with metastatic NSCLC, the 5-year survival rate is 6%. Therefore, development of a new therapeutic agent or strategy is urgent for NSCLCs. Berberine has been illustrated to be a therapeutic agent of NSCLC. In the present study, we synthesized six derivatives of berberine, and the anti-NSCLC activity of these agents was examined. Some of them exert increasing proliferation inhibition comparing with berberine. Further studies demonstrated that two of the most effective agents, 9-O-decylberberrubine bromide (B6) and 9-O-dodecylberberrubine bromide (B7), performed cell cycle regulation, in-vitro tumorigenesis inhibition and autophagic flux blocking, but not induction of cellular apoptosis in NSCLC cells. Moreover, B6 and B7 were determined to be green fluorescent and could be penetrated and localized in cellular mitochondria. Herein, B6 and B7, the berberine derivatives we synthesized, revealed better anti-NSCLC activity with berberine and may be used as therapeutic candidates for the treatment of NSCLCs.

scholarly journals Guaiazulene Triggers ROS-Induced Apoptosis and Protective Autophagy in Non-small Cell Lung Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Qin Ye ◽  
Li Zhou ◽  
Ping Jin ◽  
Lei Li ◽  
Shuwen Zheng ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Molecular Mechanisms ◽  
Small Cell ◽  
Autophagic Flux ◽  
Small Cell Lung ◽  
Induced Apoptosis

Non-small cell lung cancer (NSCLC) is one of the most frequent cancers worldwide, yet effective treatment remains a clinical challenge. Guaiazulene (GYZ), a cosmetic color additive, has previously been characterized as a potential antitumor agent due to observed anticancer effects. However, the efficacy of GYZ in the treatment of NSCLC and the involved molecular mechanisms remain largely unknown. Here, we indicated a role for GYZ in the suppression of NSCLC both in vitro and in vivo via triggering reactive oxygen species (ROS)-induced apoptosis. Concomitantly, GYZ induced complete autophagic flux in NSCLC cells via inhibiting the Akt/mTOR signaling pathway, which displayed cytoprotective effect against GYZ-induced growth suppression. Accompanied with autophagy inhibition obviously enhanced the effects of GYZ. Notably, GYZ acts synergistically with paclitaxel in the suppression of NSCLC in vitro. Together, our results for the first time reported that GYZ suppressed the proliferation of NSCLC and suggested a potential strategy for inhibiting NSCLC growth by combinational use of GYZ and autophagy inhibitors.

Phanginin R Induces Cytoprotective Autophagy via JNK/c-Jun Signaling Pathway in Non-Small Cell Lung Cancer A549 Cells

2020 ◽  
Vol 20 (8) ◽  
pp. 982-988 ◽  
Author(s):  
Le-Le Zhang ◽  
Han Bao ◽  
Yu-Lian Xu ◽  
Xiao-Ming Jiang ◽  
Wei Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Signaling Pathway ◽  
Cell Lung Cancer ◽  
Biological Activities ◽  
A549 Cells ◽  
Immunofluorescence Assay ◽  
Small Cell ◽  
Autophagic Flux ◽  
Small Cell Lung

Background: Cassane-type diterpenoids are widely distributed in the medical plants of genus Caesalpinia. To date, plenty of cassane diterpenoids have been isolated from the genus Caesalpinia, and some of them were documented to exhibit multiple biological activities. However, the effects of these compounds on autophagy have never been reported. Objective: To investigate the effects and mechanisms of the cassane diterpenoids including Phanginin R (PR) on autophagy in Non-Small Cell Lung Cancer (NSCLC) A549 cells. Methods: Western blot analysis and immunofluorescence assay were performed to investigate the effects of the compounds on autophagic flux in A549 cells. The pathway inhibitor and siRNA interference were used to investigate the mechanism of PR. MTT assay was performed to detect cell viability. Results: PR treatment upregulated the expression of phosphatidylethanolamine-modified microtubule-associated protein Light-Chain 3 (LC3-II) in A549 cells. Immunofluorescence assay showed that PR treatment increased the production of red-fluorescent puncta in mRFP-GFP-LC3 plasmid-transfected cells, indicating PR promoted autophagic flux in A549 cells. PR treatment activated the c-Jun N-terminal Kinase (JNK) signaling pathway while it did not affect the classical Akt/mammalian Target of Rapamycin (mTOR) pathway. Pretreatment with the JNK inhibitor SP600125 or siRNA targeting JNK or c-Jun suppressed PR-induced autophagy. In addition, cotreatment with the autophagy inhibitor Chloroquine (CQ) or inhibition of the JNK/c-Jun signaling pathway increased PR-induced cytotoxicity. Conclusion: PR induced cytoprotective autophagy in NSCLC A549 cells via the JNK/c-Jun signaling pathway, and autophagy inhibition could further improve the anti-cancer potential of PR.

Investigation of in vitro Activities of Cu2ZnSnS4 Nanoparticles in Human Non-Small Cell Lung Cancer

2021 ◽  
pp. 102304
Author(s):  
Suleyman Gokhan Colak ◽  
Canan Vejselova Sezer ◽  
Ruken Esra Demirdogen ◽  
Mine Ince ◽  
Fatih Mehmet Emen ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung

scholarly journals Elevating CDCA3 levels in non-small cell lung cancer enhances sensitivity to platinum-based chemotherapy

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Katrina Kildey ◽  
Neha S. Gandhi ◽  
Katherine B. Sahin ◽  
Esha T. Shah ◽  
Eric Boittier ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Genome Instability ◽  
Small Cell ◽  
Small Cell Lung ◽  
Protein Levels ◽  
Platinum Based Chemotherapy ◽  
Platinum Agents

AbstractPlatinum-based chemotherapy remains the cornerstone of treatment for most non-small cell lung cancer (NSCLC) cases either as maintenance therapy or in combination with immunotherapy. However, resistance remains a primary issue. Our findings point to the possibility of exploiting levels of cell division cycle associated protein-3 (CDCA3) to improve response of NSCLC tumours to therapy. We demonstrate that in patients and in vitro analyses, CDCA3 levels correlate with measures of genome instability and platinum sensitivity, whereby CDCA3high tumours are sensitive to cisplatin and carboplatin. In NSCLC, CDCA3 protein levels are regulated by the ubiquitin ligase APC/C and cofactor Cdh1. Here, we identified that the degradation of CDCA3 is modulated by activity of casein kinase 2 (CK2) which promotes an interaction between CDCA3 and Cdh1. Supporting this, pharmacological inhibition of CK2 with CX-4945 disrupts CDCA3 degradation, elevating CDCA3 levels and increasing sensitivity to platinum agents. We propose that combining CK2 inhibitors with platinum-based chemotherapy could enhance platinum efficacy in CDCA3low NSCLC tumours and benefit patients.

scholarly journals Mimicking Tumor Hypoxia in Non-Small Cell Lung Cancer Employing Three-Dimensional In Vitro Models

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 141
Author(s):  
Iwona Ziółkowska-Suchanek
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Tumor Hypoxia ◽  
Three Dimensional ◽  
In Vitro Models ◽  
Small Cell ◽  
Small Cell Lung ◽  
Multicellular Tumor Spheroid

Hypoxia is the most common microenvironment feature of lung cancer tumors, which affects cancer progression, metastasis and metabolism. Oxygen induces both proteomic and genomic changes within tumor cells, which cause many alternations in the tumor microenvironment (TME). This review defines current knowledge in the field of tumor hypoxia in non-small cell lung cancer (NSCLC), including biology, biomarkers, in vitro and in vivo studies and also hypoxia imaging and detection. While classic two-dimensional (2D) in vitro research models reveal some hypoxia dependent manifestations, three-dimensional (3D) cell culture models more accurately replicate the hypoxic TME. In this study, a systematic review of the current NSCLC 3D models that have been able to mimic the hypoxic TME is presented. The multicellular tumor spheroid, organoids, scaffolds, microfluidic devices and 3D bioprinting currently being utilized in NSCLC hypoxia studies are reviewed. Additionally, the utilization of 3D in vitro models for exploring biological and therapeutic parameters in the future is described.

scholarly journals Tumour-derived exosomal lncRNA-SOX2OT promotes bone metastasis of non-small cell lung cancer by targeting the miRNA-194-5p/RAC1 signalling axis in osteoclasts

2021 ◽  
Vol 12 (7) ◽  
Author(s):  
Jianjiao Ni ◽  
Xiaofei Zhang ◽  
Juan Li ◽  
Zhiqin Zheng ◽  
Junhua Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Bone Metastasis ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Osteoclast Differentiation ◽  
Small Cell ◽  
Signalling Pathway ◽  
Small Cell Lung

AbstractBone is a frequent metastatic site of non-small cell lung cancer (NSCLC), and bone metastasis (BoM) presents significant challenges for patient survival and quality of life. Osteolytic BoM is characterised by aberrant differentiation and malfunction of osteoclasts through modulation of the TGF-β/pTHrP/RANKL signalling pathway, but its upstream regulatory mechanism is unclear. In this study, we found that lncRNA-SOX2OT was highly accumulated in exosomes derived from the peripheral blood of NSCLC patients with BoM and that patients with higher expression of exosomal lncRNA-SOX2OT had significantly shorter overall survival. Additionally, exosomal lncRNA-SOX2OT derived from NSCLC cells promoted cell invasion and migration in vitro, as well as BoM in vivo. Mechanistically, we discovered that NSCLC cell-derived exosomal lncRNA-SOX2OT modulated osteoclast differentiation and stimulated BoM by targeting the miRNA-194-5p/RAC1 signalling axis and TGF-β/pTHrP/RANKL signalling pathway in osteoclasts. In conclusion, exosomal lncRNA-SOX2OT plays a crucial role in promoting BoM and may serve as a promising prognostic biomarker and treatment target in metastatic NSCLC.

scholarly journals Docetaxel-loaded exosomes for targeting non-small cell lung cancer: preparation and evaluation in vitro and in vivo

Drug Delivery ◽  
2021 ◽  
Vol 28 (1) ◽  
pp. 1510-1523
Author(s):  
Ying Wang ◽  
Mimi Guo ◽  
Dingmei Lin ◽  
Dajun Liang ◽  
Ling Zhao ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Preparation And Evaluation
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