The tocotrienol-rich fraction from rice bran enhances cisplatin-induced cytotoxicity in human mesothelioma H28 cells

Our plain-English summary of The tocotrienol-rich fraction from rice bran enhances cisplatin-induced cytotoxicity in human mesothelioma H28 cells, by K. Nakashima, N. Virgona, M. Miyazawa, et al (Phytotherapy Research, 2010).

The study

• Authors: K. Nakashima, N. Virgona, M. Miyazawa, T. Watanabe, T. Yano
• Journal: Phytotherapy Research
• Published: 2010;24(9):1317-21
• Cited by: 20 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Resistance to chemotherapy (chemoresistance) is a serious problem in malignant mesothelioma, a highly aggressive neoplasm. Gamma-tocotrienol (gamma-T3) can sensitize various cancerous cells to chemotherapeutic agents by inhibiting pathways that lead to treatment resistance. In this study, we investigated the modulating effect of tocotrienol-rich fraction (TRF) from rice bran, which is abundant in gamma-T3, on chemoresistance in human MM H28 cells. TRF treatment caused a marked reduction in the viability of H28 cells in a dose-dependent manner, while cisplatin treatment had no effect on the cells, indicating that H28 cells are resistant to cisplatin. A significant increase in cytotoxicity was observed in H28 cells treated with TRF, and this effect was enhanced by the combination treatment with cisplatin. The cytotoxic effect was closely related to the inhibition of phosphatidylinositol 3-kinase (PI3K)-AKT signaling. Inactivation of Akt signaling by TRF or the combination with cisplatin mitigated cisplatin-induced activation of Akt, resulting in reducing the chemoresistance H28 cells to cisplatin. Reduced cell viability and attenuated chemoresistance of the H28 cells against cisplatin were also observed following the use of a PI3K inhibitor, LY294002. These results suggest that the combination therapy of cisplatin with TRF is a plausible strategy for achieving tolerance for the chemotherapeutic agent in MM therapy.

Copyright 2010 John Wiley & Sons, Ltd.

In plain English

This was a laboratory study of cancer cells grown in dishes. It did not involve patients or asbestos exposure. The authors tested a vitamin E-rich rice bran extract, the tocotrienol-rich fraction (TRF), on H28 cells. H28 is a human malignant mesothelioma cell line the authors describe as cisplatin-resistant. Gamma-tocotrienol made up 39.3% of the extract. TRF at 0 to 40 micrograms per millilitre slowed growth more as the dose rose, up to a plateau, and 10 micrograms per millilitre cut viability by 50%. Cisplatin alone did not slow the cells' growth at the doses tested. Combining cisplatin (1.5 micromolar) with TRF inhibited growth. Caspase 3, a marker of programmed cell death, rose with TRF and further with the combination. Cisplatin increased activation of a cell-survival signal called Akt, while TRF markedly reduced it. The pathway blocker LY294002 also slowed growth. The authors concluded that combining cisplatin with TRF seems promising for mesothelioma treatment. They noted the effective TRF dose (about 10 micromolar gamma-tocotrienol) exceeds reported blood gamma-tocotrienol levels (about 1 to 2 micromolar) after high oral doses, so bioavailability needs addressing.

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: laboratory cell-culture (in vitro) experiment
• Who was studied: H28, a human malignant mesothelioma cell line obtained from ATCC, described as resistant to cisplatin; no patients were studied
• Exposure: Treatments applied to the cells, not asbestos: a tocotrienol-rich fraction (TRF) extracted from rice bran (39.3% gamma-tocotrienol by weight), the chemotherapy drug cisplatin (1.5 micromolar in combination tests), and the PI3K inhibitor LY294002
• Main results:
  • In H28 cells, TRF at 0 to 40 micrograms per millilitre inhibited cell growth in a dose-dependent way, although the inhibition reached a plateau
  • In H28 cells, TRF at 10 micrograms per millilitre reduced cell viability by 50%
  • H28 cells were resistant to cisplatin given alone at the doses used: cisplatin alone did not inhibit their growth
  • In H28 cells, the combination of cisplatin (1.5 micromolar) with TRF (10 micrograms per millilitre) inhibited growth
  • In H28 cells, cisplatin alone did not change caspase 3 activity (a marker of programmed cell death); TRF increased it, and the combination with cisplatin increased it further
  • In H28 cells, cisplatin increased activation of the survival signal Akt, while TRF markedly reduced Akt activation (immunoblot shown as representative of two independent experiments)
  • In H28 cells, changes in phosphorylation of Bad, a molecule regulated by Akt, closely followed the changes in Akt activation
  • In H28 cells, the PI3K/Akt inhibitor LY294002 suppressed growth depending on its concentration, and its combination with cisplatin inhibited cell growth
• The authors' conclusion: The authors concluded that combination therapy of cisplatin with TRF seems to be promising as a new therapeutic strategy for malignant mesothelioma
• Limitations the authors state:
  • The authors noted that the effective TRF dose, equivalent to about 10 micromolar gamma-tocotrienol, is higher than the reported plasma gamma-tocotrienol levels of about 1 to 2 micromolar after high oral doses of tocotrienol-rich vitamin E, so bioavailability of gamma-tocotrienol needs to be improved

Topics

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

Medical terms in this study, explained in our Lexicon: Cisplatin, Mesothelioma, Chemotherapy, Malignant Mesothelioma, Neoplasm.

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