scholarly journals The antitumor effects of mitochondria-targeted 6-(nicotinamide) methyl coumarin

2016 ◽  
Vol 11 (1) ◽  
pp. 542-551
Author(s):  
Huanan Wang ◽  
Ming Yao ◽  
Wenqing Xu
Keyword(s):  
Lung Cancer ◽  
Proliferative Activity ◽  
A549 Cells ◽  
Signaling Cascades ◽  
Antitumor Drugs ◽  
Coumarin Derivatives ◽  
Mitochondrial Depolarization ◽  
Antitumor Effects ◽  
Mitochondria Membrane Potential ◽  
Mitochondrial Signaling

AbstractCancer is the second leading cause of death worldwide. Traditional antitumor drugs exhibit severe cytotoxic and side effects. Lung cancer needs new and more effective treatment approaches. Coumarin derivatives can act on various tumor cells and show anti-proliferative activity through various mechanisms, including mitochondrial signaling cascades that regulate development and apoptosis of cells. Mitochondria-targeted coumarin derivatives have not been reported yet. Taking advantage of the fact that cancer cells frequently have higher mitochondria membrane potential, we synthesized a mitochondria-targeted 6-(nicotinamide) methyl coumarin by coupling 6-methyl coumarin to nicotinamide. Our results demonstrate that 6-(nicotinamide) methyl coumarin preferentially kills A549 cells through inducing A549 cells apoptosis, mediated by increasing ROS level and causing mitochondrial depolarization. Strikingly, the viability of the A31 cells treated with 6-(nicotinamide) methyl coumarin did not decrease, indicating that 6-(nicotinamide) methyl coumarin preferentially accumulates in A549 cells and A549 cells are much more susceptible to 6-(nicotinamide) methyl coumarin treatment compared with A31 cells.

The Superior Antitumor Effect of Self-Assembled Paclitaxel Nanofilaments for Lung Cancer Cells

2018 ◽  
Vol 16 (2) ◽  
pp. 171-178
Author(s):  
Mengyu He ◽  
Jiali Zhu ◽  
Na Yu ◽  
Hui Kong ◽  
Xiaoning Zeng ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Cancer Cells ◽  
Antitumor Effect ◽  
Stress Proteins ◽  
A549 Cells ◽  
Lung Cancer Cells ◽  
Antitumor Effects ◽  
Self Assembled

Objectives: Paclitaxel (Ptx) has been regarded as one of the most effective chemotherapeutic drugs for lung cancers. Increasing studies focused on the nano-delivery system of Ptx due to its poor solubility and hypersensitivity. The aim of the recent study was to investigate the antitumor effects of self-assembled Ptx nano-filaments for lung cancer cells. </P><P> Methods: In the present study, we designed and synthesized novel Ptx-loaded nano-filaments through conjugation of Ptx and succinic acid (SA) (Ptx-SA, P-NFs). Non-small cell lung cancer (NSCLC) A549 and H460 cells were used for detecting the antitumor effects of P-NFs, including cytotoxicity, apoptosis, and migration. Western blotting was performed for analyzing mechanism. Results: P-NFs nano-filaments exerted superior antitumor effects against NSCLC cells compared with free Ptx using cytotoxicity tests. Furthermore, P-NFs nano-filaments were much more effective in inducing NSCLC cells apoptosis and inhibiting A549 cells migration than free Ptx. To elucidate the underlying mechanisms, the expression of apoptotic and endoplasmic reticulum (ER) stress proteins was detected. The results indicated that P-NFs nano-filaments enhanced the expression of bax/bcl-2, protein kinase RNA-like endoplasmic reticulum kinase (PERK), inositol-requiring enzyme 1&#945; (IRE1&#945;), phospho- c-Jun N-terminal kinase (p-JNK), and C/EPB homologous protein (CHOP), which suggested that the strong antitumor effect of P-NFs nano-filaments may be partially attributed to the activation ER stress. The current work demonstrated that P-NFs nano-filaments showed superior cytotoxicity of lung cancer cells, highlighting a novel profile of nano-filaments delivery systems as potential strategies for facilitating the therapeutic efficacy of Ptx in lung cancer treatment.

scholarly journals Enhancement of Anti-Proliferative Activity of the Extracts from Dehulled Adlay by Fermentation with Bacillus subtilis

Foods ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 2959
Author(s):  
Anyan Wen ◽  
Yong Zhu ◽  
Muhammad Mazhar ◽  
Likang Qin ◽  
Haiying Zeng ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Bacillus Subtilis ◽  
Tumor Cells ◽  
Proliferative Activity ◽  
A549 Cells ◽  
K562 Cells ◽  
Human Leukemia ◽  
Bioactive Components ◽  
Butanol Extract ◽  
Ferulic Acids

Dehulled adlay was fermented with Bacillus subtilis BJ3-2, the anti-proliferative activities of the extracts from fermented dehulled adlay were investigated with six types of tumor cells, and then the bioactive components and the anti-proliferative mechanism were primarily explored. Results showed that all the extracts of B. subtilis-fermented dehulled adlay (BDA) and dehulled adlay (DA) had no inhibition effect on human embryonic kidney 239T cells. The anti-proliferative activities of the extracts from BDA against six types of tumor cells were almost always significantly higher than DA. Compared with others, the n-butanol extract of BDA (BDA-Nb) exhibited stronger anti-proliferative activities against human leukemia K562 cells and human non-small cell lung cancer A549 cells. Importantly, the anti-proliferative activity of fermented dehulled adlay against K562 cells was firstly discovered. Meanwhile, BDA-Nb was rich in tetramethylpyrazine, γ-aminobutyric acid, protocatechuic, 2,3,4-trihydroxybenzoic, chlorogenic, p-hydroxybenzoic, caffeic, trans-cinnamic, ferulic acids, and rutin. BDA-Nb induced the proliferative inhibition of K562 and A549 cells due to abnormal cell morphology, the increased cell population in G1 phase and apoptosis rate, the downregulation of Bcl-2, and the upregulation of Bax and caspase-3/8/9. These results indicate that dehulled adlay fermented with B. subtilis could be a potential therapeutic agent for leukemia and lung cancer.

Piperine induces apoptosis of lung cancer A549 cells via p53-dependent mitochondrial signaling pathway

Tumor Biology ◽  
2013 ◽  
Vol 35 (4) ◽  
pp. 3305-3310 ◽  
Author(s):  
Yi Lin ◽  
Jianping Xu ◽  
Hehe Liao ◽  
Lu Li ◽  
Lei Pan
Keyword(s):  
Lung Cancer ◽  
Signaling Pathway ◽  
A549 Cells ◽  
Mitochondrial Signaling

scholarly journals Diallyl Disulfide Attenuates Ionizing Radiation-Induced Migration and Invasion by Suppressing Nrf2 Signaling in Non–small-Cell Lung Cancer

Dose-Response ◽  
2021 ◽  
Vol 19 (3) ◽  
pp. 155932582110331
Author(s):  
Shuai Xu ◽  
Hefa Huang ◽  
Deping Tang ◽  
Mengjie Xing ◽  
Qiuyue Zhao ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Ionizing Radiation ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
A549 Cells ◽  
Small Cell ◽  
Migration And Invasion ◽  
Diallyl Disulfide ◽  
Small Cell Lung ◽  
Antitumor Effects

Non–small-cell lung cancer (NSCLC) is the leading cause of cancer-associated deaths. Radiotherapy remains the primary treatment method for NSCLC. Despite great advances in radiotherapy techniques and modalities, recurrence and resistance still limit therapeutic success, even low-dose ionizing radiation (IR) can induce the migration and invasion. Diallyl disulfide (DADS), a bioactive component extracted from garlic, exhibits a wide spectrum of biological activities including antitumor effects. However, the effect of DADS on IR-induced migration and invasion remains unclear. The present study reported that IR significantly promoted the migration and invasion of A549 cells. Pretreatment with 40 μM DADS enhanced the radiosensitivity of A549 cells and attenuated IR-induced migration and invasion. In addition, 40 μM DADS inhibited migration-related protein matrix metalloproteinase-2 and 9 (MMP-2/9) expression and suppressed IR-aggravated EMT by the upregulation of the epithelial marker, E-cadherin, and downregulation of the mesenchymal marker, N-cadherin, in A549 cells. Furthermore, DADS was found to inhibit the activation of Nrf2 signaling. Based on our previous results that knockdown of Nrf2 by siRNA suppressed IR-induced migration and invasion in A549 cells, we speculated that DADS attenuated IR-induced migration and invasion by suppressing the activation of Nrf2 signaling in A549 cells.

scholarly journals Inhibitory Effect of pH-Responsive Nanogel Encapsulating Ginsenoside CK against Lung Cancer

Polymers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 1784
Author(s):  
Ziyang Xue ◽  
Rongzhan Fu ◽  
Zhiguang Duan ◽  
Lei Chi ◽  
Chenhui Zhu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Water Solubility ◽  
Drug Loading ◽  
Survival Rates ◽  
A549 Cells ◽  
Ph Responsive ◽  
Antitumor Effects ◽  
Hydrophobic Cavity

Ginsenoside CK is one of the intestinal bacterial metabolites of ginsenoside prototype saponins, such as ginsenoside Rb1, Rb2, Rc, and Rd. Poor water solubility and low bioavailability have limited its application. The nanogel carriers could specifically deliver hydrophobic drugs to cancer cells. Therefore, in this study, a nanogel was constructed by the formation of Schiff base bonds between hydrazide-modified carboxymethyl cellulose (CMC-NH2) and aldehyde-modified β-cyclodextrin (β-CD-CHO). A water-in-oil reverse microemulsion method was utilized to encapsulate ginsenoside CK via the hydrophobic cavity of β-CD. β-CD-CHO with a unique hydrophobic cavity carried out efficient encapsulation of CK, and the drug loading and encapsulation efficiency were 16.4% and 70.9%, respectively. The drug release of CK-loaded nanogels (CK-Ngs) in vitro was investigated in different pH environments, and the results showed that the cumulative release rate at pH 5.8 was 85.5% after 140 h. The methylthiazolyldiphenyl-tetrazolium bromide (MTT) toxicity analysis indicated that the survival rates of A549 cells in CK-Ngs at 96 h was 2.98% compared to that of CK (11.34%). In vivo animal experiments exhibited that the inhibitory rates of CK-Ngs against tumor volume was 73.8%, which was higher than that of CK (66.1%). Collectively, the pH-responsive nanogel prepared herein could be considered as a potential nanocarrier for CK to improve its antitumor effects against lung cancer.

scholarly journals Terpinen-4-ol Induces Apoptosis in Human Nonsmall Cell Lung Cancer In Vitro and In Vivo

2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Chieh-Shan Wu ◽  
Yun-Ju Chen ◽  
Jeremy J. W. Chen ◽  
Jeng-Jer Shieh ◽  
Chia-Hsin Huang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Lung Cancer ◽  
Molecular Mechanisms ◽  
A549 Cells ◽  
Annexin V ◽  
Nonsmall Cell Lung Cancer ◽  
Antitumor Effects ◽  
Apoptotic Pathway

Terpinen-4-ol, a monoterpene component of the essential oils of several aromatic plants, exhibits antitumor effects. In this study, the antitumor effects of terpinen-4-ol and the cellular and molecular mechanisms responsible for it were evaluated and studied, respectively on human nonsmall cell lung cancer (NSCLC) cells. Our results indicated that terpinen-4-ol elicited a dose-dependent cytotoxic effect, as determined by MTT assay. Increased sub-G1 population and annexin-V binding, activation of caspases 9 and 3, cleavage of poly(ADPribose) polymerase (PARP), and a decrease of mitochondrial membrane potential (MMP) indicated involvement of the mitochondrial apoptotic pathway in terpinen-4-ol-treated A549 and CL1-0 cells. Elevation of the Bax/Bcl-2 ratio and a decrease in IAP family proteins XIAP and survivin were also observed following terpinen-4-ol treatment. Notably, terpinen-4-ol was able to increase p53 levels in A549 and CL1-0 cells. Diminution of p53 by RNA interference induced necrosis instead of apoptosis in A549 cells following terpinen-4-ol treatment, indicating that terpinen-4-ol-elicited apoptosis is p53-dependent. Moreover, intratumoral administration of terpinen-4-ol significantly suppressed the growth of s.c. A549 xenografts by inducing apoptosis, as confirmed by TUNEL assay. Collectively, these data provide insight into the molecular mechanisms underlying terpinen-4-ol-induced apoptosis in NSCLC cells, rendering this compound a potential anticancer drug for NSCLC.

scholarly journals Oridonin Improves the Therapeutic Effect of Lentinan on Lung Cancer

2021 ◽  
Author(s):  
Yun Gui ◽  
Jing Cheng ◽  
Zhiguo Chen
Keyword(s):  
Lung Cancer ◽  
Protein Expression ◽  
Cell Viability ◽  
Cell Line ◽  
A549 Cell ◽  
A549 Cells ◽  
Cancer Drug ◽  
Mice Model ◽  
Antitumor Effects ◽  
Mrna And Protein Expression

Abstract Oridonin, a compound from Rabdosia rubescens, has been shown to have a potency for the improvement of the antitumor effect of lentinan (LNT). In this study, we tested the effect of oridonin, LNT, and the combination of them on a normal human fetal lung fibroblast cell line MRC-5 and non-small cell lung cancer cell line A549. Then we tested their effects on metastasis and survival with a lung cancer mice model. The effects of them on the mRNA and protein expression of several regulatory factors in A549 and lung tissue were determined by QPCR and western blotting. Results showed that the viability of MRC-5 and A549 were not affected by 0-20 µg/ml oridonin. 0-300 µg/ml LNT did not affect the viability of MRC-5, but 50-400 µg/ml LNT inhibited the viability of A549. 20 µg/ml oridonin and 100 or 300 µg/ml LNT were used in the subsequent study. The oridonin, LNT, or the combination of both had no effect on MRC-5 cell viability. The oridonin had no effect on A549 cell viability but LNT suppressed A549 cell viability, and oridonin promoted the suppression of LNT on A549 cells. In vivo study showed that oridonin alone had no effect on metastasis and survival but LNT decreased metastasis and survival in mice. Oridonin improved the suppression of LNT against metastasis and further improved the survival rate. In both A549 and lung tissues, LNT increased the mRNA and protein expression of caspase-3, caspase-8, caspase-9, Bax, p53, p21, and IκB-α, reduced mRNA and protein expressions of Bcl-2 and NF-κB. Oridonin enhanced all the effects of LNT on cells. Our study demonstrated that oridonin enhanced the antitumor effects of LNT and is conducive to the development of oridonin and LNT as a novel cancer drug regimen.

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