Effect of Tocotrienols isomers on the Viability of Oral Cancer Cells (ORL-48): An MTT Assay Study

Authors

  • Rahayu Zulkapli Cardiovascular Advancement and Research Excellence Institute (CARE Institute), Universiti Teknologi MARA, Selangor, Malaysia
  • Khor Goot Heah Oral and Maxillofacial Cancer Research, Universiti Teknologi MARA Sungai Buloh Campus, Jalan Hospital, 47000 Sungai Buloh, Selangor, Malaysia
  • Nur Shahinaz Mahadi Faculty of Dentistry, Universiti Teknologi MARA Sungai Buloh Campus, Jalan Hospital, 47000 Sungai Buloh, Selangor, Malaysia
  • Wan Fatimah Wan Fatul Faculty of Dentistry, Universiti Teknologi MARA Sungai Buloh Campus, Jalan Hospital, 47000 Sungai Buloh, Selangor, Malaysia
  • Atiqa Syazwani Ridzuan Faculty of Dentistry, Universiti Teknologi MARA Sungai Buloh Campus, Jalan Hospital, 47000 Sungai Buloh, Selangor, Malaysia

DOI:

https://doi.org/10.24191/cos.v12i2.8831

Keywords:

tocotrienols, antiproliferative, oral cancer, oral squamous cell carcinoma, cytotoxicity

Abstract

Objectives: This study aimed to conduct an in vitro investigation to evaluate the viability of tocotrienol isomers (α, β, γ, δ) on human oral squamous cell carcinoma (OSCC), specifically targeting the ORL-48 cell line, using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Methods: The MTT assay is a widely used colorimetric assay for measuring the cytotoxic effects of potential medicinal or active compounds. Technical triplicates were employed in this study to ensure the reliability and reproducibility of the results. Results: Among the tocotrienol isomers tested, γ-tocotrienol demonstrated significant viability inhibition, with an IC50 of 5.2 ± 1.4 µg/mL on the ORL-48 cell line. In contrast, the IC50 values for α, β, and δ tocotrienols were not determinable (ND), as their percentage of inhibition was less than 50%, indicating a lack of significant effect at the tested concentrations. Conclusions: These findings suggest that γ-tocotrienol has potential as an antiproliferative agent against oral cancer cells (ORL-48). Its significant activity underscores the need for further functional studies to better understand its mechanisms of action and potential therapeutic roles in future cancer treatment. Future research should focus on elucidating the molecular pathways effects of γ-tocotrienol and exploring its.

References

Abubakar, I. B., Lim, K. H., Kam, T. S., & Loh, H. S. (2017). Enhancement of apoptotic activities on brain cancer cells via the combination of γ-tocotrienol and jerantinine A. Phytomedicine, 30, 74–84.

Aggarwal, V., Kashyap, D., Sak, K., Tuli, H. S., Jain, A., Chaudhary, A., Garg, V. K., Sethi, G., & Yerer, M. B. (2019). Molecular mechanisms of action of tocotrienols in cancer: Recent trends and advancements. International Journal of Molecular Sciences, 20(3), 656. https://doi.org/10.3390/ijms20030656.

American Cancer Society. (2024, April 4). Global cancer statistics, 2024. https://pressroom.cancer.org/Global-Cancer-Statistics-2024.

Burton, G. W., & Traber, M. G. (1990). Vitamin E: Antioxidant activity, biokinetics, and bioavailability. Annual Review of Nutrition, 10, 357–382. 10.1146/annurev.nu. https://doi.org/10.070190.002041.

Chow, M., & Rubin, H. (1998). Selective killing of preneoplastic and neoplastic cells by methotrexate with leucovorin. Proceedings of the National Academy of Sciences, 95(8), 4550–4555. https://doi.org/10.1073/pnas.95.8.4550.

Farouk Musa, A. (2021). Tocotrienol: An underrated isomer of vitamin E in health and diseases. In Biochemistry. IntechOpen.

Ferlay, J., Ervik, M., Lam, F., Colombet, M., Mery, L., Pineros, M., Znaor, A., Soerjomataram, I., & Bray, F. (2021, June 6). Global Cancer Observatory: Cancer tomorrow. International Agency for Research on Cancer. https://gco.iarc.fr/tomorrow.

Husain, K., Centeno, B. A., Coppola, D., Trevino, J., Sebti, S. M., & Malafa, M. P. (2017). δ-Tocotrienol, a natural form of vitamin E, inhibits pancreatic cancer stem-like cells and prevents pancreatic cancer metastasis. Oncotarget, 8(19), 31554–31567. https://doi.org/10.18632/oncotarget.15767.

International Agency for Research on Cancer. (2024, April 4). New report on global cancer burden in 2022 by world region and human development level. https://www.iarc.who.int/news-events/new-report-on-global-cancer-burden-in-2022-by-world-region-and-human-development-level/.

Kani, K., Momota, Y., Harada, M., Yamamura, Y., Aota, K., Yamanoi, T., Takano, H., Motegi, K., & Azuma, M. (2013). γ-Tocotrienol enhances the chemosensitivity of human oral cancer cells to docetaxel through the downregulation of the expression of NF-κB-regulated anti-apoptotic gene products. International Journal of Oncology, 42(1), 75–82. https://doi.org/10.3892/ijo.2012.1692.

Narimah, A. H. H., Ghapor, M. T. A., Khalid, B. A. K., & Wan Ngah, W. Z. (2009). Anti-proliferation effect of palm oil γ-tocotrienol and α-tocopherol on cervical carcinoma and hepatoma cell apoptosis. Biomedical Research, 20(3), 180.

Rajasinghe, L. D., Pindiprolu, R. H., & Gupta, S. V. (2018). Delta-tocotrienol inhibits non-small-cell lung cancer cell invasion via the inhibition of NF-κB, uPA activator, and MMP-9. OncoTargets and Therapy, 11, 4301–4314. https://doi.org/10.2147/OTT.S160163l.

Ridzuan, A. S., Amin, I. M., Heah, K. G., & Zulkapli, R. (2020). Vitamin E isomers and cancer research: A review. Asia-Pacific Journal of Molecular Biology and Biotechnology, 30(3), 1–10. https://doi.org/10.35118/apjmbb.2022.030.3.01.

Sailo, B. L., Banik, K., Padmavathi, G., Javadi, M., Bordoloi, D., & Kunnumakkara, A. B. (2018). Tocotrienols: The promising analogues of vitamin E for cancer therapeutics. Pharmacological Research, 129, 259-272. https://doi.org/10.1016/j.phrs.2018.02.017.

Sen, C. K., Khanna, S., Rink, C., & Roy, S. (2007). Tocotrienols: The emerging face of natural vitamin E. Vitamins and Hormones, 76, 203–261. https://doi.org/10.1016/S0083-6729(07)76008-9.

Syairah, N. S., Rawaidah, N. M. S., Froemming, G. R. A., Amin, I. M., Yusof, M. Y. P. M., & Khor, G. H. (2017). IC50 of Ganoderma lucidum extract on oral cancer cells, ORL-48T. Journal of Fundamental and Applied Sciences, 9(6S), 237–245. https://doi.org/10.4314/jfas.v9i6s.19.

Tan, B. (2017). Vitamin E: A closer look at tocotrienols. Nutritional Outlook, 20(8), 1–4.

Wu, S. J., & Ng, L. T. (2010). Tocotrienols inhibited growth and induced apoptosis in human HeLa cells through the cell cycle signaling pathway. Integrative Cancer Therapies, 9(1), 66–72. https://doi.org/10.1177/1534735409357757.

Zulkapli, R., Abdul Razak, F., & Zain, R. B. (2017). Vitamin E (α-tocopherol) exhibits antitumour activity on oral squamous carcinoma cells ORL-48. Integrative Cancer Therapies, 16(3), 414–425. https://doi.org/10.1177/1534735416675950.

Downloads

Published

2025-09-01

How to Cite

Zulkapli, R., Heah, K. G., Mahadi, N. S., Wan Fatul, W. F., & Ridzuan, A. S. (2025). Effect of Tocotrienols isomers on the Viability of Oral Cancer Cells (ORL-48): An MTT Assay Study. Compendium of Oral Science, 12(2), 80–88. https://doi.org/10.24191/cos.v12i2.8831

Issue

Vol. 12 No. 2 (2025): Compendium of Oral Science

Section

Original Article

License

Copyright (c) 2025 Compendium of Oral Science

Creative Commons License

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

Materials contained in the journal may be reproduced for educational purposes provided that both the author(s) and the journal are appropriately recognised; otherwise duplication is not permitted. No articles, reports, or portions there of may be translated into other languages, published in books, journals, magazines, or any other print form without written permission from the authors and from the journal.

Disclaimer: The statements, opinions and data expressed in the articles and reports herein are those of the author(s) and not of the publisher and the editor(s). The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any schemes, methods, instructions or ideas referred to in the content.