Liposome mediated-CYP1A1 gene silencing nanomedicine prepared using lipid film-coated proliposomes as a potential treatment strategy of lung cancer

[Display omitted] The occurrence of lung cancer is linked with tobacco smoking, mainly through the generation of polycyclic aromatic hydrocarbons (PAHs). Elevated activity of cytochrome P4501A1 (CYP1A1) plays an important role in the metabolic processing of PAHs and its carcinogenicity. The present...

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Published inInternational journal of pharmaceutics Vol. 566; pp. 185 - 193
Main Authors Zhang, Mengtian, Wang, Qin, Wan, Ka-Wai, Ahmed, Waqar, Phoenix, David A., Zhang, Zhirong, Elrayess, Mohamed A., Elhissi, Abdelbary, Sun, Xun
Format Journal Article
LanguageEnglish
Published Netherlands Elsevier B.V 20.07.2019
Subjects
A549 Cells
Animals
Apoptosis
Cancer
CYP1A1
Cytochrome P-450 CYP1A1 - genetics
Gene Silencing
Humans
Lipids
Liposomes
Lung
Lung Neoplasms - genetics
Lung Neoplasms - pathology
Lung Neoplasms - therapy
Male
Methylcholanthrene - toxicity
Mice, Inbred BALB C
Mice, Nude
Nanomedicine
RNA, Messenger
RNA, Small Interfering - administration & dosage
siRNA
Smoking
Tobacco
Tobacco
Lung
CYP1A1
siRNA
Apoptosis
Cancer
Smoking
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Abstract [Display omitted] The occurrence of lung cancer is linked with tobacco smoking, mainly through the generation of polycyclic aromatic hydrocarbons (PAHs). Elevated activity of cytochrome P4501A1 (CYP1A1) plays an important role in the metabolic processing of PAHs and its carcinogenicity. The present work aimed to investigate the role of CYP1A1 gene in PAH-mediated growth and tumor development in vitro and using an in vivo animal model. RNAi strategy was utilized to inhibit the overexpression of CYP1A1 gene using cationic liposomes generated using a lipid film-coated proliposome microparticles. Treatment of PAH-induced human alveolar adenocarcinoma cell line with cationic liposomes carrying CYP1A1 siRNA resulted in down regulation of CYP1A1 mRNA, protein as well as its enzymatic activity, triggering apoptosis and inhibiting multicellular tumor spheroids formation in vitro. Furthermore, silencing of CYP1A1 gene in BALB/c nude xenografts inhibited tumor growth via down regulation of CYP1A1 expression. Altogether, our findings showed that liposome-based gene delivery technology is a viable and stable approach for targeting cancer causing genes such as CY1PA1. This technology facilitated by the use of sugar particles coated with lipid films has demonstrated ability to generate anticancer effects that might be used in the future for therapeutic intervention and treatment of lung cancer.
AbstractList The occurrence of lung cancer is linked with tobacco smoking, mainly through the generation of polycyclic aromatic hydrocarbons (PAHs). Elevated activity of cytochrome P4501A1 (CYP1A1) plays an important role in the metabolic processing of PAHs and its carcinogenicity. The present work aimed to investigate the role of CYP1A1 gene in PAH-mediated growth and tumor development in vitro and using an in vivo animal model. RNAi strategy was utilized to inhibit the overexpression of CYP1A1 gene using cationic liposomes generated using a lipid film-coated proliposome microparticles. Treatment of PAH-induced human alveolar adenocarcinoma cell line with cationic liposomes carrying CYP1A1 siRNA resulted in down regulation of CYP1A1 mRNA, protein as well as its enzymatic activity, triggering apoptosis and inhibiting multicellular tumor spheroids formation in vitro. Furthermore, silencing of CYP1A1 gene in BALB/c nude xenografts inhibited tumor growth via down regulation of CYP1A1 expression. Altogether, our findings showed that liposome-based gene delivery technology is a viable and stable approach for targeting cancer causing genes such as CY1PA1. This technology facilitated by the use of sugar particles coated with lipid films has demonstrated ability to generate anticancer effects that might be used in the future for therapeutic intervention and treatment of lung cancer.
[Display omitted] The occurrence of lung cancer is linked with tobacco smoking, mainly through the generation of polycyclic aromatic hydrocarbons (PAHs). Elevated activity of cytochrome P4501A1 (CYP1A1) plays an important role in the metabolic processing of PAHs and its carcinogenicity. The present work aimed to investigate the role of CYP1A1 gene in PAH-mediated growth and tumor development in vitro and using an in vivo animal model. RNAi strategy was utilized to inhibit the overexpression of CYP1A1 gene using cationic liposomes generated using a lipid film-coated proliposome microparticles. Treatment of PAH-induced human alveolar adenocarcinoma cell line with cationic liposomes carrying CYP1A1 siRNA resulted in down regulation of CYP1A1 mRNA, protein as well as its enzymatic activity, triggering apoptosis and inhibiting multicellular tumor spheroids formation in vitro. Furthermore, silencing of CYP1A1 gene in BALB/c nude xenografts inhibited tumor growth via down regulation of CYP1A1 expression. Altogether, our findings showed that liposome-based gene delivery technology is a viable and stable approach for targeting cancer causing genes such as CY1PA1. This technology facilitated by the use of sugar particles coated with lipid films has demonstrated ability to generate anticancer effects that might be used in the future for therapeutic intervention and treatment of lung cancer.
Author Zhang, Zhirong
Elhissi, Abdelbary
Wan, Ka-Wai
Elrayess, Mohamed A.
Sun, Xun
Zhang, Mengtian
Ahmed, Waqar
Wang, Qin
Phoenix, David A.
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Keywords Tobacco
Lung
CYP1A1
siRNA
Apoptosis
Cancer
Smoking
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Snippet [Display omitted] The occurrence of lung cancer is linked with tobacco smoking, mainly through the generation of polycyclic aromatic hydrocarbons (PAHs)....
The occurrence of lung cancer is linked with tobacco smoking, mainly through the generation of polycyclic aromatic hydrocarbons (PAHs). Elevated activity of...
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SubjectTerms A549 Cells
Animals
Apoptosis
Cancer
CYP1A1
Cytochrome P-450 CYP1A1 - genetics
Gene Silencing
Humans
Lipids
Liposomes
Lung
Lung Neoplasms - genetics
Lung Neoplasms - pathology
Lung Neoplasms - therapy
Male
Methylcholanthrene - toxicity
Mice, Inbred BALB C
Mice, Nude
Nanomedicine
RNA, Messenger
RNA, Small Interfering - administration & dosage
siRNA
Smoking
Tobacco
Title Liposome mediated-CYP1A1 gene silencing nanomedicine prepared using lipid film-coated proliposomes as a potential treatment strategy of lung cancer
URI https://dx.doi.org/10.1016/j.ijpharm.2019.04.078
https://www.ncbi.nlm.nih.gov/pubmed/31051230
Volume 566
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