Anti‐proliferative effects of γ‐tocotrienol on mammary tumour cells are associated with suppression of cell cycle progression

Abstract

Treatment with 4 micromgamma-tocotrienol significantly inhibited +SA cell proliferation over a 4-day culture period. Moreover, this treatment resulted in a relatively large reduction in cyclin D1, cyclin dependent kinase (CDK)4, CDK2 and CDK6 levels, between 4 and 24 h after EGF exposure. Tocotrienol treatment also resulted in a relatively large increase in CDK inhibitor (CKI) p27, prior to and after EGF exposure, but had little effect on levels of CKIs, p21 and p15. Tocotrienol treatment also induced a large relative reduction in retinoblastoma (Rb) protein phosphorylation at ser780 and ser807/811. These findings strongly suggest that anti-proliferative effects of gamma-tocotrienol are associated with reduction in cell cycle progression from G(1) to S, as evidenced by increased p27 levels, and a corresponding decrease in cyclin D1, CDK2, CDK4, CDK6 and phosphorylated Rb levels.

γ-Tocotrienol reduces human airway smooth muscle cell proliferation and migration

“…Zhang et al reported that g-tocotrienol produces dosedependent inhibition of colon cancer cell growth [43]. g-tocotrienol also inhibits proliferation of pancreatic cancer cells [44], breast cancer cell lines [45,46], and prostate cancer cell lines [47].…”

Tocotrienols fight cancer by targeting multiple cell signaling pathways

“…Park et al (2010) Suppressed preneoplastic mammary epithelial cell proliferation Sylvester et al (2002) Exhibited synergism with erlotinib/gefitinib in suppressing cell proliferation Bachawal et al (2010) Inhibited cell growth irrespective of estrogen receptor status Nesaretnam et al (1998) Exhibited antiproliferation and induced apoptosis by DNA fragmentation McIntyre et al (2000a), McIntyre et al (2000b), Comitato et al (2009) Induced apoptosis in tumor cells through endoplasmic reticulum stress Park et al (2010) Induced apoptosis through TGF-b/Fas/JNK-signaling pathway Shun et al (2004) Reduced PI3K/PDK-1/Akt signaling Sylvester et al (2005) Inhibited cell proliferation and induced apoptosis Shah and Sylvester (2004), Shah and Sylvester (2005b), Sylvester and Shah (2005b), Samant et al (2010) Induced apoptosis through activation of caspases Shah et al (2003), Sylvester and Shah (2005a) Suppressed cell proliferation and down-regulated Bcl-2 and cyclin D1 Hsieh and Wu (2008) Inhibited ER-negative and ER-positive cell proliferation Guthrie et al (1997), Nesaretnam et al (1995) Inhibited proliferation by arresting cell cycle progression Samant et al (2010), Wali et al (2009a) Inhibited tumor cell growth by suppressing HMGR activity Wali et al (2009b) Induced apoptosis through mitochondria-mediated death pathway Takahashi and Loo (2004) Inhibited proliferation through down-regulation of Id1 protein Reduced cell viability and induced apoptosis via the mitochondrial pathway Pierpaoli et al …”

First Evidence That γ-Tocotrienol Inhibits the Growth of Human Gastric Cancer and Chemosensitizes It to Capecitabine in a Xenograft Mouse Model through the Modulation of NF-κB Pathway

“…However, while tocopherols had been intensively studied for their health benefits, many novel benefits of tocotrienols are only beginning to be brought to light by research in the last decade (13,14). For instance, g-tocotrienol has been reported to suppress the proliferation of a wide variety of tumor cells (15), including gastric (16)(17)(18)(19), hepatocellular carcinoma (20), melanoma (21), breast (22), colorectal (23), and prostate (24). In vivo mice studies have shown that g-tocotrienol can suppress the growth of breast tumor (25), prostate (26), lung cancer and melanoma (27) and also inhibit the growth of liver and pancreatic cancer either alone or in combination with chemotherapeutic drugs and radiation (28,29).…”