Breast cancer is the second most frequent cancer affecting women worldwide after lung cancer. The toxicity factor associated with synthetic drugs has turned the attention toward natural compounds as the primary focus of interest as anticancer agents. Vitamin E derivatives consisting of the well-established tocopherols and their analogs namely tocotrienols have been extensively studied due to their remarkable biological properties. While tocopherols have failed to offer protection, tocotrienols, in particular, α-, δ-, and γ-tocotrienols alone and in combination have demonstrated anticancer properties. The discovery of the antiangiogenic, antiproliferative, and apoptotic effects of tocotrienols, as well as their role as an inducer of immunological functions, not only reveals a new horizon as a potent antitumor agent but also reinforces the notion that tocotrienols are indeed more than antioxidants. On the basis of a transcriptomic platform, we have recently demonstrated a novel mechanism for tocotrienol activity that involves estrogen receptor (ER) signaling. In silico simulations and in vitro binding analyses indicate a high affinity of specific forms of tocotrienols for ERβ, but not for ERα. Moreover, we have demonstrated that specific tocotrienols increase ERβ translocation into the nucleus which, in turn, activates the expression of estrogen-responsive genes (MIC-1, EGR-1 and Cathepsin D) in breast cancer cells only expressing ERβ cells (MDA-MB-231) and in cells expressing both ER isoforms (MCF-7). The binding of specific tocotrienol forms to ERβ is associated with the alteration of cell morphology, caspase-3 activation, DNA fragmentation, and apoptosis. Furthermore, a recently concluded clinical trial seems to suggest that tocotrienols in combination with tamoxifen may have the potential to extend breast cancer-specific survival.
Keywords: Tocotrienols, Anticancer, Antiproliferative, Tamoxifen, Apoptosis, Chemopreventive
Pertengahan tahun ini sebelum berlepas ke Australia untuk bercuti, penulis terlibat dengan penyediaan perjanjian projek dengan agensi luar negara yang antara lain membuat kajian mengenai kesan toksik ubat-ubat kanser. Ya - ianya tersangat toksik, hinggakan menurut penyelidik yang menjalankan kajian, badan manusia hanya boleh tolerate berapa miligram per body weight sahaja. Maka setelah sampai tahap selamat penggunaan sesuatu ubat, pesakit tidak akan dibenarkan lagi menggunakan ubat tersebut buat SELAMA-LAMANYA! Macam tu la pula jadinya.... dan pada masa yang sama juga ibu penulis telah ditahan di wad Hospital Universiti kerana dijadualkan memulakan chemo....
Demi Allah... kalau bukan sebab mesyuarat yang membincangkan masa depan dan possible breakthrough untuk mengubati kanser, dah tentu diri ini akan meninggalkan sahaja bilik mesyuarat masa tu.
Ya Allah berikanlah kami kekuatan Iman untuk menempuhi semua ini. Aaminn.
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