A Redox-Inactive Derivative of Tocotrienol Suppresses Tumor Growth of Mesothelioma Cells in a Xenograft Model

Our plain-English summary of A Redox-Inactive Derivative of Tocotrienol Suppresses Tumor Growth of Mesothelioma Cells in a Xenograft Model, by A. Sato, T. Arai, M. Fusegi, et al (Biological & Pharmaceutical Bulletin, 2019).

The study

• Authors: A. Sato, T. Arai, M. Fusegi, A. Ando, T. Yano
• Journal: Biological & Pharmaceutical Bulletin
• Published: 2019;42(6):1034-1037
• Cited by: 5 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant mesothelioma (MM) is an aggressive cancer with poor prognosis. We focused on the anticancer activity of tocotrienol (T3) and have reported that a new redox-inactive T3 derivative (6-O-carboxypropyl-α-tocotrienol; T3E) exerts stronger inhibitory effects on MM cell growth than that of T3 in vitro. Furthermore, we have revealed some mechanisms of T3E that are involved in anti-MM effects. However, the effect of T3E in vivo remains unclear. In this study, we compared the plasma concentrations of T3E to that of T3 using mice to clarify differences in pharmacokinetics. Blood was sequentially collected after oral administration of T3 or T3E, and plasma concentrations were analyzed by HPLC. The area under the plasma T3 and T3E concentration-time curve from 0 to 24 h (AUC0-24 h) of T3E was two times higher than that of T3. In addition, we evaluated the effect of T3E oral administration on tumor growth using a xenograft model of mice that were transplanted with human MM cells (H2052 cell line). Tumor volume was significantly reduced without body weight loss in mice orally administered 150 mg/kg T3E once per 2 d for 10 d, which suggests that T3E has potential anti-MM effects.

In plain English

This laboratory study in mice tested T3E (6-O-carboxypropyl-α-tocotrienol), a lab-made derivative of tocotrienol, a member of the vitamin E family, as a possible mesothelioma drug. It involved no people and did not study asbestos exposure. First, groups of four male mice received one oral dose of 100 mg/kg of tocotrienol or T3E, and blood levels were measured over 24 hours. Peak blood levels were similar (mean 22.2 µmol/L for tocotrienol, 19.5 µmol/L for T3E). T3E peaked later (6 hours versus 3 hours). Its plasma exposure over 24 hours, measured as the area under the concentration–time curve, was about two times higher. Second, nude mice were injected under the skin with a human pleural mesothelioma cell line (H2052). They then received by mouth, every 2 days for 10 days, either 150 mg/kg T3E in vitamin E-stripped corn oil or that oil alone. In the T3E group, tumor volume was significantly reduced and tumor weight decreased, while body weight was not affected. The authors concluded that T3E is a new agent to treat mesothelioma. They noted that long-term toxicity testing is needed before clinical use.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Animal experiment: a pharmacokinetic comparison in mice plus a xenograft tumor-growth study in nude mice (published as a short Note)
• Who was studied: Male ICR mice (n = 4) were used for the blood-level study. Male BALB/c-nu nude mice (n = 8 per the figure legend) were injected under the skin of the back with the human malignant pleural mesothelioma cell line H2052. Experiments were approved by Chiba University, Japan. Dates are not given.
• Exposure: Blood-level study: a single oral dose of 100 mg/kg tocotrienol (T3) or T3E in tocopherol-stripped corn oil. Tumor study: oral T3E 150 mg/kg, or tocopherol-stripped corn oil alone as the control, given once every 2 days for 10 days. No asbestos exposure was studied.
• Main results:
  • After a single 100 mg/kg oral dose, peak plasma concentrations were 22.2 ± 5.3 µmol/L for T3 and 19.5 ± 3.5 µmol/L for T3E (mean ± standard error, n = 4).
  • Time to peak plasma concentration was 3 h for T3 and 6 h for T3E.
  • The area under the plasma concentration–time curve from 0 to 24 h was about two times higher for T3E than for T3 (p less than 0.01 vs. T3, per the figure legend).
  • T3 was not detected in plasma after T3E was given.
  • In nude mice carrying H2052 tumors, tumor volume was significantly reduced and tumor weight was decreased in the T3E group compared with controls (n = 8). Numerical tumor values are shown only in figures.
  • Body weight was not affected in the T3E-treated mice.
• The authors' conclusion: The authors concluded that the results suggest T3E has an anti-tumor effect with less toxicity in mice. They described T3E as a new agent to treat malignant mesothelioma, based on the non-antioxidant functions of tocotrienol.
• Limitations the authors state:
  • The authors state that further studies, including toxicity testing with long-term T3E administration, are needed before clinical use.
  • The authors state that further investigation of T3E's tissue distribution and metabolism is needed.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Mesothelioma, Malignant Mesothelioma, Prognosis.

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