Abstract

Mantle cell lymphoma (MCL) is considered clinically aggressive and an incurable subtype of B-cell non-Hodgkin lymphoma (NHL) with poor prognosis and resistance to conventional therapies. This has prompted increasing interest in novel therapeutic approaches, particularly those derived from natural sources with multi-targeted mechanisms of action and low systemic toxicity. In recent years, plant-derived essential oils and their bioactive compounds have emerged as promising therapeutic agents for MCL due to their bioactive properties and low systemic toxicity. Therefore, the purpose of this study was to investigate the growth inhibitory effect of essential oils from basil, tea tree, turmeric and black pepper against mantle cell lymphoma cell lines (REC1R288, REC1Scrambled) and investigate the potential for induction of apoptosis, aiming to identify the signalling pathways involved in the growth inhibition for the promising chemical constituents D-limonene, linalool, ß-Caryophyllene, α-pinene, and D-3-carene.The selected essential oils were analysed using GC-MS analysis which showed that the main effective components for basil oil were linalool, eugenol and 1,8 cineol. However, α-pinene, ß-Caryophyllene, D-3-carene, and D-limonene were the main effective components for black pepper, turmeric and tea tree oils. Combining a range of cell culture, biochemical and molecular techniques, the work presented describes the inhibitory effect of these essential oils against mantle cell lymphoma cell lines (REC1R288, REC1 Scrambled) using trypan blue, MTT and Alamar blue assay. Alamar blue was found to be more sensitive and convenient for assessing cell viability. REC1R288 cell line was more sensitive to essential oils in comparison to REC1Scrambled which may be due to CCN1 knockdown in the REC1R288 cell line as shown in Alamar blue experiments. Of the essential oils tested, Basil oil showed the maximal growth inhibition with 66-70 % for REC1R288 and 53-59% for REC1Scrambled. Moreover, cell cycle analysis using propidium iodide (PI) demonstrated that Turmeric oil induced G0-G1 arrest for both cell lines while Sub G0-G1 was induced by black pepper, tea tree, and basil oil. Interestingly, black pepper, turmeric, and basil oil significantly induced late apoptosis via Annexin-V+/PI-. Since essential oils are essentially a mixture of numerous chemical components it is important to determine which chemical component(s) has the anticancer effect. D-limonene, linalool, ß-Caryophyllene, α-pinene, and D-3-carene all are showed an inhibitory effect on REC1R288 and REC1Scrambled cells. These bioactive compounds may have cytotoxic effects on MCL cells through diverse molecular pathways, including the induction of mitochondrial-dependent apoptosis, caspase-3 cleavage and PARP cleavage. D-limonene has been shown to induce both apoptotic and paraptotic cell death by triggering endoplasmic reticulum (ER) stress, leading to vacuolization and disruption of intracellular homeostasis. Linalool has induced apoptosis via metabolic pathway while ß-Caryophyllene targeted apoptosis by inhibiting the glycolysis process. D-3-carene inhibited TDP1 expression for both cell lines. Importantly, these phytochemicals have shown synergistic effects when combined with standard chemotherapeutic agents, enhancing drug sensitivity and overcoming resistance in MCL cells. Their ability to target multiple hallmarks of cancer, including proliferation, evasion of apoptosis, and metabolic dysregulation, makes them attractive candidates for integrative cancer therapy.In conclusion, the plant-derived bioactive compounds tested exhibited considerable promise as adjunctive or standalone agents in the pharmacological management of mantle cell lymphoma. Continued research into their molecular mechanisms, optimal formulations, and combinatory effects with existing therapies are required and preclinical and clinical studies are necessary to translate these findings into viable treatment options for MCL patients.

Awarding Institution(s)

University of Plymouth

Supervisor

Lynn McCallum, Mick Fuller

Document Type

Thesis

Publication Date

2026

Embargo Period

2026-09-11

Deposit Date

September 2026

Creative Commons License

Creative Commons Attribution-NonCommercial 4.0 International License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License

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