Palm tocotrienols inhibit proliferation of murine mammary cancer cells and induce expression of interleukin-24 mRNA.
Several mechanisms have been postulated for the anticancer effects of tocotrienols. In this study, for the first time, the anticancer effect of tocotrienols is linked to increased expression of interleukin-24 (IL-24) mRNA, a cytokine reported to have antitumor effects in many cancer models. Tocotrienol isomers (α-T3, γ-T3, and δ-T3) and tocotrienol-rich fraction (TRF) inhibited the growth of the 4T1 murine mammary cancer cells (P < 0.05), with IC₅₀ values 8.99, 4.79, 3.73, and 8.63 μg/mL, respectively. Tumor incidence and tumor load in TRF-supplemented BALB/c mice was decreased by 57.1% and 93.6% (P < 0.05), respectively. The induction of the IL-24 mRNA in the 4T1 cells by vitamin E decreased in the following order: δ-T3 > γ-T3 > TRF > α-T3 > α-T, which was similar to their antiproliferative effects. The IL-24 mRNA levels in tumor tissues of BALB/c mice supplemented with TRF increased 2-fold when compared with control mice. Increased levels of IL-24 have been associated with inhibition of tumor growth and angiogenesis. Treatment of 4T1 cells with TRF and δ-T3 significantly decreased IL-8 and vascular endothelial growth factor mRNA levels. Hence, we report that tocotrienols have potent antiangiogenic and antitumor effects that is associated with increased levels of IL-24 mRNA.
Product Development and Advisory Services, Malaysian Palm Oil Board, Kajang, Selangor, Malaysia. krani@mpob.gov.my
Kanga Rani
KR
Selvaduray
Ammu K
AK
Radhakrishnan
Methil Kannan
MK
Kutty
Kalanithi
K
Nesaretnam
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004354:Drug Screening Assays, Antitumor; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D007378:Interleukins / Q000235:genetics* / Q000276:immunology; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008968:Molecular Conformation; D010938:Plant Oils / Q000737:chemistry* / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013237:Stereoisomerism; D024508:Tocotrienols / Q000737:chemistry / Q000494:pharmacology*; D000099180:Interleukin-24
D000970:Antineoplastic Agents; D007378:Interleukins; D010938:Plant Oils; D012333:RNA, Messenger; D024508:Tocotrienols; D000099180:Interleukin-24