4.7 Article

Geraniol exerts its antiproliferative action by modulating molecular targets in lung and skin carcinoma cells

Journal

PHYTOTHERAPY RESEARCH
Volume 35, Issue 7, Pages 3861-3874

Publisher

WILEY
DOI: 10.1002/ptr.7094

Keywords

cancer; Ehrlich Ascites Carcinoma; geraniol; hyaluronidase; molecular targets; monoterpenes

Funding

  1. Council of Scientific and Industrial Research-Aroma Mission Project [HCP 007]

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Geraniol, a acyclic monoterpene found in plant essential oils, has shown potent antiproliferative and antitumor effects through its antiinflammatory and antioxidant properties. Molecular and cell-based assays revealed its ability to inhibit cancer cell proliferation, affect gene expression, and interact with molecular targets. In animal models, geraniol demonstrated tumor growth inhibition and displayed safety at certain concentrations, suggesting its potential as a novel anticancer agent.
Geraniol, an acyclic monoterpene present in several plant species' essential oils, is utilized as a food additive. It possesses potent antiproliferative and antitumor effects ascribed to its antiinflammatory, and antioxidant properties. The study aimed to understand geraniol's mechanism in human lung and skin cancer cells by employing molecular and cell target-based assays. SRB, NRU, MTT assays, qRT-PCR, molecular docking, and EAC model were used. Geraniol inhibits the proliferation of PC-3, A431, and A549 cells (similar to 50%) and suppresses the activity of ornithine decarboxylase (15.42 +/- 0.61 mu M) and hyaluronidase (57.61 +/- 8.53 04) in A549 cells; LOX-5 (25.44 +/- 3.50 04) and hyaluronidase (90.71 +/- 2.38 mu M) in A431 cells. The qRT-expression analysis of the targeted gene depicts non-significant change at the transcriptional level of LOX-5 in A431 cells. A robust binding interaction of geraniol with molecular targets was observed in the molecular docking studies. In Ehrlich Ascites Carcinoma model, geraniol inhibit tumor growth by 50.08% at 75 mg/kg bw and was found to be safe up to 1,000 mg/kg bw in a toxicity study. Geraniol has two prenyl units allied head-to-tail and functionalized with one hydroxyl group at its tail end could be responsible for the antiproliferative activity. These observations provide evidence for geraniol to be used as a new prototype to develop a novel anticancer agent.

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