Mevalonate-suppressive tocotrienols for cancer chemoprevention and adjuvant therapy

Huanbiao Mo, Manal Elfakhani, Anureet Shah, Hoda Yeganehjoo

Research output: Chapter in Book/Report/Conference proceedingChapter

4 Scopus citations

Abstract

The tumor-suppressive activity of tocotrienols, vitamin E molecules with an unsaturated isoprenoid side chain, has been extensively reviewed in the previous edition of this book (Mo and Elson 2008). Tocotrienols at physiologically attainable concentrations suppress the proliferation of tumor cells derived from breast, liver, prostate, skin, colon, blood, lung, lymph gland, cervix, and nerve. Tocotrienol-mediated growth suppression is attributed to cell cycle arrest, mostly at the G1 phase of cell cycle, and apoptosis. Signaling pathways associated with promoting cell cycle progression, growth, and survival, including mitogen-activated protein kinases (MAPK), Ras, RhoA, Raf/MAPK kinase (MEK)/extracellular signal-regulated kinases (ERK), c-Jun, c-myc, cyclin D/cdk4, protein kinase C (PKC), phosphatidylinositol 3-kinase (PI3K), Akt, IκB kinase (IKK), IκB, nuclear factor κB (NFκB), c-Jun N-terminal kinase (JNK), Bcl-2, Bcl-xL, COX-2, matrix metalloproteinases (MMP), vascular endothelial growth factor (VEGF), FLIP, and telomerase, are suppressed by tocotrienols. On the other hand, signaling activities supporting growth arrest and apoptosis, including p21cip1WAF1, transforming growth factor-β (TGF-β), p53, Fas, Bax, Apaf-1, caspases, and Bid fragmentation, are activated by tocotrienols. Animal models with chemically initiated carcinogenesis and implanted tumors confirmed the in vitro tumor-suppressive activity of tocotrienols. Differing from statins, the nondiscriminant competitive inhibitors of 3-hydroxy-3-methyglutaryl coenzyme A (HMG CoA) reductase, tocotrienols are downregulators of the activity of HMG CoA reductase. Dysregulation of HMG CoA reductase in tumors offers a unique target for tumor-specific intervention. Recent literature continues to support the potential of tocotrienols as tumor-targeted agents in cancer chemoprevention and/or therapy.

Original languageEnglish (US)
Title of host publicationTocotrienols
Subtitle of host publicationVitamin E beyond Tocopherols, Second Edition
PublisherCRC Press
Pages135-150
Number of pages16
ISBN (Electronic)9781439884430
ISBN (Print)9781439884416
DOIs
Publication statusPublished - Jan 1 2012

    Fingerprint

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Engineering(all)
  • Agricultural and Biological Sciences(all)

Cite this

Mo, H., Elfakhani, M., Shah, A., & Yeganehjoo, H. (2012). Mevalonate-suppressive tocotrienols for cancer chemoprevention and adjuvant therapy. In Tocotrienols: Vitamin E beyond Tocopherols, Second Edition (pp. 135-150). CRC Press. https://doi.org/10.1201/b12502