Increase in resistance to anticancer drugs involves occludin in spheroid culture model of lung adenocarcinoma A549 cells

Eguchi, Hiroaki; Akizuki, Risa; Maruhashi, Ryohei; Tsukimoto, Mitsutoshi; Furuta, Takumi; Matsunaga, Toshiyuki; Endo, Shunsuke; Ikari, Akira

doi:10.1038/s41598-018-33566-w

Cited by 15 publications

(11 citation statements)

References 35 publications

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“…The in vitro inhibitory effects of the compounds were measured by MTT assay [ 59 , 60 ]. Briefly, cells were plated in 96-well plates at a density of 1 × 10 4 cells/well.…”

Section: Methodsmentioning

confidence: 99%

Synthesis, Biological Activity, and Molecular Modelling Studies of Naphthoquinone Derivatives as Promising Anticancer Candidates Targeting COX-2

et al. 2022

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Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-associated mortalities worldwide. Therefore, it is crucial to develop a novel therapeutic option targeting localized and metastatic NSCLC. In this paper, we describe the synthesis and biological activity characterization of naphthoquinone derivatives bearing selective anticancer activity to NSCLC via a COX-2 mediated pathway. The biological evaluation of compounds 9–16 showed promising structure-dependent anticancer activity on A549 cells in 2D and 3D models. Compounds were able to significantly (p < 0.05) reduce the A549 viability after 24 h of treatment in comparison to treated control. Compounds 9 and 16 bearing phenylamino and 4-hydroxyphenylamino substituents demonstrated the most promising anticancer activity and were able to induce mitochondrial damage and ROS formation. Furthermore, most promising compounds showed significantly lower cytotoxicity to non-cancerous Vero cells. The in silico ADMET properties revealed promising drug-like properties of compounds 9 and 16. Both compounds demonstrated favorable predicted GI absorption values, while only 16 was predicted to be permeable through the blood–brain barrier. Molecular modeling studies identified that compound 16 is able to interact with COX-2 in arachidonic acid site. Further studies are needed to better understand the safety and in vivo efficacy of compounds 9 and 16.

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“…The in vitro inhibitory effects of the compounds were measured by MTT assay [ 59 , 60 ]. Briefly, cells were plated in 96-well plates at a density of 1 × 10 4 cells/well.…”

Section: Methodsmentioning

confidence: 99%

Synthesis, Biological Activity, and Molecular Modelling Studies of Naphthoquinone Derivatives as Promising Anticancer Candidates Targeting COX-2

et al. 2022

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“…Occludin contains a transmembrane domain with four membrane-spanning regions and other protein domains such as a C-terminus coiled-coil domain to interact with other proteins [ 200 , 203 ] . OCLN’s protein expression can influence the development of several cancer types, including ovarian cancer [ 200 ] , lung adenocarcinoma [ 203 , 205 ] , and breast cancer metastasis [ 206 ] . Zhang et al [ 200 ] (2018) reported that OCLN overexpression increased transepithelial resistance, which indicates stronger TJs, while downregulation of OCLN resulted in a decreased cell to cell adhesion phenotype (a common characteristic of tumors).…”

Section: Cancer Drug Resistance Related Genesmentioning

confidence: 99%

“…The overexpression of OCLN induces drug resistance by inhibiting the flux of doxorubicin, thus lowering drug concentration within the cell. OCLN may not be related to cancer drug resistance acquisition directly, but it limits the chemosensitivity of anticancer drugs to lung cancer cells [ 205 ] .…”

Section: Cancer Drug Resistance Related Genesmentioning

confidence: 99%

“…OCLN overexpression on A549 cells decreased doxorubicin permeability due to their effect on signaling pathways, lowering the drug’s accumulation and cytotoxicity, leading to anticancer drug resistance. Interestingly, spheroid cancer cells with an increased OCLN expression developed cisplatin resistance, showing the importance of this gene in MDR [ 205 ] .…”

Section: Cancer Drug Resistance Related Genesmentioning

confidence: 99%

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Key genes and drug delivery systems to improve the efficiency of chemotherapy

Torres‐Martínez¹,

Delgado²,

Ferrer-Acosta³

et al. 2020

CDR

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Cancer cells can develop resistance to anticancer drugs, thereby becoming tolerant to treatment through different mechanisms. The biological mechanisms leading to the generation of anticancer treatment resistance include alterations in transmembrane proteins, DNA damage and repair mechanisms, alterations in target molecules, and genetic responses, among others. The most common anti-cancer drugs reported to develop resistance to cancer cells include cisplatin, doxorubicin, paclitaxel, and fluorouracil. These anticancer drugs have different mechanisms of action, and specific cancer types can be affected by different genes. The development of drug resistance is a cellular response which uses differential gene expression, to enable adaptation and survival of the cell to diverse threatening environmental agents. In this review, we briefly look at the key regulatory genes, their expression, as well as the responses and regulation of cancer cells when exposed to anticancer drugs, along with the incorporation of alternative nanocarriers as treatments to overcome anticancer drug resistance.

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“…Although these cell culture models help answer some of the key questions, they may accompany multifactorial complexities. For example, the nonuniformity in the spheroid size contributes to the poor reproducibility of the cell response to cytotoxic drugs [9,10]. Also, large spheroids are devoid of any vasculature in the middle and hence the potential failure of drug delivery to the entire multicellular spheroid could be an important factor in reduced chemosensitivity rather than cellular resistance [11].…”

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confidence: 99%

Bioimprinting: Bringing Together 2D and 3D in Dissecting Cancer Biology

Sarwar

Evans

2021

BioTechniques

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2D plus experiments • cancer research • cell culture model • physiological cues • signal transduction Basic cell biology researchIn recent years, the role of the extracellular matrix (ECM) in cellular functions and tissue homeostasis has been well acknowledged [1]. ECM represents a major constituent of tissue architecture, arranged into a 3D network secreted by various stromal cells, composed of a diverse range of fibrous and nonfibrous, and structural and nonstructural proteins, accompanied by polysaccharides. Several in vitro cell culture models that can mimic the ECM features have been introduced to investigate tumor biology, such as different 3D cell culture models. Distinct versions of 3D culture models using hydrogels [2], collagen, Matrigel [3], nonadherent surfaces [4,5] and engineered scaffolds [6][7][8] have emerged. Current in vitro cell culture modelsGenerally, 3D culture models are considered to have a better resemblance to the in vivo physiological extracellular environment than traditional 2D cell culture models. Although these cell culture models help answer some of the key questions, they may accompany multifactorial complexities. For example, the nonuniformity in the spheroid size contributes to the poor reproducibility of the cell response to cytotoxic drugs [9,10]. Also, large spheroids are devoid of any vasculature in the middle and hence the potential failure of drug delivery to the entire multicellular spheroid could be an important factor in reduced chemosensitivity rather than cellular resistance [11]. The cell culture conditions may induce certain genes to modify their expression levels and hence lead to modified cellular activities [12,13]. Therefore, in vitro cell responses, to some extent, do not truly reflect the in situ tumor cell conduct, but exhibit cell behavior associated with the given experimental conditions [14][15][16][17]. Thus, it is vital to carefully design the chosen cell culture system to investigate the given hypotheses. According to the principle of Occam's razor, attributed to William of Ockham in the early 14th century, the simplest answer is often the best answer.

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Increase in resistance to anticancer drugs involves occludin in spheroid culture model of lung adenocarcinoma A549 cells

Cited by 15 publications

References 35 publications

Synthesis, Biological Activity, and Molecular Modelling Studies of Naphthoquinone Derivatives as Promising Anticancer Candidates Targeting COX-2

Synthesis, Biological Activity, and Molecular Modelling Studies of Naphthoquinone Derivatives as Promising Anticancer Candidates Targeting COX-2

Key genes and drug delivery systems to improve the efficiency of chemotherapy

Bioimprinting: Bringing Together 2D and 3D in Dissecting Cancer Biology

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