Anticancer and Antioxidant Properties of Terpinolene in Rat Brain Cells

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Abstract

Terpinolene (TPO) is a natural monoterpene present in essential oils of many aromatic plant species. Although various biological activities of TPO have been demonstrated, its neurotoxicity has never been explored. In this in vitro study we investigated TPO’s antiproliferative and/or cytotoxic properties using the 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) test, genotoxic damage potential using the single-cell gel electrophoresis (SCGE), and oxidative effects through total antioxidant capacity (TAC) and total oxidative stress (TOS) in cultured primary rat neurons and N2a neuroblastoma cells. Dose-dependent effects of TPO (at 10 mg L-1, 25 mg L-1, 50 mg L-1, 100 mg L-1, 200 mg L-1, and 400 mg L-1) were tested in both cell types. Significant (P<0.05) decrease in cell proliferation were observed in cultured primary rat neurons starting with the dose of 100 mg L-1 and in N2a neuroblastoma cells starting with 50 mg L-1. TPO was not genotoxic in either cell type. In addition, TPO treatment at 10 mg L-1, 25 mg L-1, and 50 mg L-1 increased TAC in primary rat neurons, but not in N2a cells. However, at concentrations above 50 mg L-1 it increased TOS in both cell types. Our findings clearly demonstrate that TPO is a potent antiproliferative agent for brain tumour cells and may have potential as an anticancer agent, which needs to be further studied.

Sažetak

PROTUTUMORSKA I ANTIOKSIDATIVNA SVOJSTVA TERPINOLENA U MOŽDANIH STANICA ŠTAKORA

Terpinolen (TPO) prirodni je monoterpen prisutan u esencijalnim uljima mnogih aromatskih biljaka. Premda su otprije poznate razne biološke aktivnosti TPO-a, dosad nije ispitana njegova neurotoksičnost. Svrha je ovog istraživanja in vitro bila utvrditi antiproliferacijska i/ili citotoksična svojstva TPO-a pomoću testa 3-(4,5-dimetiltiazol-2-yl)-2,5 difeniltetrazolijeva bromida (MTT), njegov genotoksični potencijal pomoću komet-testa te oksidativno djelovanje kroz ukupni antioksidativni kapacitet i ukupni oksidativni stres u uzgojenim primarnim neuronima štakora i N2a stanicama neuroblastoma. U objema staničnim linijama ispitani su učinci TPO-a u skladu sa sljedećim dozama: 10 mg L-1, 25 mg L-1, 50 mg L-1, 100 mg L-1, 200 mg L-1 i 400 mg L-1. Značajni (p<0.05) pad stanične proliferacije u primarnim neuronima štakora zamijećen je pri dozama od 100 mg L-1 naviše, a u N2a stanicama neuroblastoma pri dozama od 50 mg L-1 naviše. Niti u jednoj staničnoj liniji TPO se nije pokazao genotoksičnim. Usto se primjenom TPO-a pri dozama od 10 mg L-1, 25 mg L-1 i 50 mg L-1 povećao ukupni antioksidativni kapacitet primarnih štakorskih neurona, ali je takvo djelovanje izostalo u N2a stanica. Međutim, pri koncentracijama višim od 50 mg L-1 TPO je povećao ukupni oksidativni stres u objema staničnim linijama. Naši rezultati nedvojbeno pokazuju da je TPO snažan antiproliferacijski agens u tumorskih stanica mozga, a njegovu potencijalnu ulogu kao protutumorskog lijeka trebalo bi dalje istraživati.

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Archives of Industrial Hygiene and Toxicology

The Journal of Institute for Medical Research and Occupational Health

Journal Information


IMPACT FACTOR 2016: 1.395

CiteScore 2016: 1.25

SCImago Journal Rank (SJR) 2016: 0.404
Source Normalized Impact per Paper (SNIP) 2016: 0.721

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