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Published on: March 30, 2019
A transcriptomic computational analysis of mastic oil-treated Lewis lung carcinomas reveals molecular mechanisms
Panagiotis Moulos1, Olga Papadodima, Aristotelis Chatziioannou
1Institute of Biological Research and Biotechnology, National Hellenic Research Foundation, Athens, Greece. pmoulos@eie.gr
Background:
Mastic oil from Pistacia lentiscus variation chia, a blend of bioactive terpenes with recognized medicinal properties, has been recently shown to exert anti-tumor growth activity through inhibition of cancer cell proliferation, survival, angiogenesis and inflammatory response. However, no studies have addressed its mechanisms of action at genome-wide gene expression level.
Methods:
To investigate molecular mechanisms triggered by mastic oil, Lewis Lung Carcinoma cells were treated with mastic oil or DMSO and RNA was collected at five distinct time points (3-48 h). Microarray expression profiling was performed using Illumina mouse-6 v1 beadchips, followed by computational analysis. For a number of selected genes, RT-PCR validation was performed in LLC cells as well as in three human cancer cell lines of different origin (A549, HCT116, K562). PTEN specific inhibition by a bisperovanadium compound was applied to validate its contribution to mastic oil-mediated anti-tumor growth effects.
Results:
In this work we demonstrated that exposure of Lewis lung carcinomas to mastic oil caused a time-dependent alteration in the expression of 925 genes. GO analysis associated expression profiles with several biological processes and functions. Among them, modifications on cell cycle/proliferation, survival and NF-kappaB cascade in conjunction with concomitant regulation of genes encoding for PTEN, E2F7, HMOX1 (up-regulation) and NOD1 (down-regulation) indicated some important mechanistic links underlying the anti-proliferative, pro-apoptotic and anti-inflammatory effects of mastic oil. The expression profiles of Hmox1, Pten and E2f7 genes were similarly altered by mastic oil in the majority of test cancer cell lines. Inhibition of PTEN partially reversed mastic oil effects on tumor cell growth, indicating a multi-target mechanism of action. Finally, k-means clustering, organized the significant gene list in eight clusters demonstrating a similar expression profile. Promoter analysis in a representative cluster revealed shared putative cis-elements suggesting a common regulatory transcription mechanism.
Conclusions:
Present results provide novel evidence on the molecular basis of tumor growth inhibition mediated by mastic oil and set a rational basis for application of genomics and bioinformatic methodologies in the screening of natural compounds with potential cancer chemopreventive activities.
Insights
Mastic oil from Pistacia lentiscus variation chia shows anti-tumor effects by altering gene expression. This study reveals its molecular mechanisms, highlighting PTEN
Area of Science:
- Genomics
- Molecular Biology
- Pharmacology
Background:
- Mastic oil from Pistacia lentiscus variation chia possesses bioactive terpenes with known medicinal properties.
- Previous studies indicated mastic oil's anti-tumor activity, inhibiting cancer cell proliferation, survival, angiogenesis, and inflammation.
- The precise molecular mechanisms at the genome-wide gene expression level remained uninvestigated.
Purpose of the Study:
- To elucidate the molecular mechanisms underlying mastic oil's anti-tumor effects.
- To investigate genome-wide gene expression changes induced by mastic oil treatment.
- To identify key genes and pathways involved in mastic oil's anti-cancer activity.
Main Methods:
- Lewis Lung Carcinoma (LLC) cells were treated with mastic oil or DMSO, with RNA collected at five time points (3-48 h).
- Microarray expression profiling was conducted using Illumina mouse-6 v1 beadchips, followed by computational analysis.
- RT-PCR validated gene expression in LLC and human cancer cell lines (A549, HCT116, K562); PTEN inhibition was used to assess its role.
Main Results:
- Mastic oil exposure altered the expression of 925 genes in a time-dependent manner.
- Gene Ontology (GO) analysis linked expression profiles to cell cycle, proliferation, survival, and NF-kappaB cascade.
- Key regulated genes included PTEN, E2F7, HMOX1 (up-regulated), and NOD1 (down-regulated), indicating anti-proliferative and anti-inflammatory effects.
- PTEN inhibition partially reversed mastic oil's anti-tumor effects, suggesting a multi-target mechanism.
Conclusions:
- This study provides novel insights into the molecular basis of tumor growth inhibition by mastic oil.
- The findings highlight the involvement of PTEN, cell cycle regulators, and inflammatory pathways.
- Genomics and bioinformatics approaches are valuable for screening natural compounds like mastic oil for cancer chemoprevention.
