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.

Highlights

  • 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

  • Significant (P

  • The addition of TPO at concentrations below 100 mg L-1 for 24 h did not cause any change in cell viability in primary rat neurons

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Summary

Introduction

Terpinolene (TPO, 1-isopropenyl-4-methylcyclohex3-ene) is a monoterpenic constituent of essential oils of plants such as Melaleuca alternifolia, Melaleuca trichostachya, Manilla elemi, Nectranda elaiophora, and Dacrydium colensoi [30,31,32].TPO has a broad spectrum of biological activities such as anticancer [33], antioxidant [34], antifungal [35], and larvacidal [36] These important biological effects have raised interest in research of the antiproliferative effects induced by several monoterpenes such as carvacrol and α-pinene on human ovarian, hepatocellular, and metastatic breast cancer cells [37, 38].

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