Fatima Ayesha, Abdul Ahmad Bustamam Hj, Abdullah Rasedee, Karjiban Roghayeh Abedi, Lee Vannajan Sanghiran
UPM-MAKNA Cancer Research Laboratory, Institute of Biosciences, University Putra Malaysia, 43400 Serdang, Malaysia.
Department of Chemistry, Faculty of Science, University Putra Malaysia, 43400 Serdang, Malaysia.
Int J Mol Sci. 2015 Jan 26;16(2):2747-66. doi: 10.3390/ijms16022747.
Breast cancer is the second most common cancer among women worldwide. Several signaling pathways have been implicated as causative and progression agents. The tumor necrosis factor (TNF) α protein plays a dual role in promoting and inhibiting cancer depending largely on the pathway initiated by the binding of the protein to its receptor. Zerumbone, an active constituent of Zingiber zerumbet, Smith, is known to act on the tumor necrosis factor pathway upregulating tumour necrosis factor related apoptosis inducing ligand (TRAIL) death receptors and inducing apoptosis in cancer cells. Zerumbone is a sesquiterpene that is able to penetrate into the hydrophobic pockets of proteins to exert its inhibiting activity with several proteins. We found a good binding with the tumor necrosis factor, kinase κB (IKKβ) and the Nuclear factor κB (NF-κB) component proteins along the TNF pathway. Our results suggest that zerumbone can exert its apoptotic activities by inhibiting the cytoplasmic proteins. It inhibits the IKKβ kinase that activates the NF-κB and also binds to the NF-κB complex in the TNF pathway. Blocking both proteins can lead to inhibition of cell proliferating proteins to be downregulated and possibly ultimate induction of apoptosis.
乳腺癌是全球女性中第二常见的癌症。有几种信号通路被认为是致癌和促进癌症进展的因素。肿瘤坏死因子（TNF）α蛋白在促进和抑制癌症方面发挥着双重作用，这在很大程度上取决于该蛋白与其受体结合所启动的信号通路。姜黄烯是莪术（Zingiber zerumbet, Smith）的一种活性成分，已知它作用于肿瘤坏死因子信号通路，上调肿瘤坏死因子相关凋亡诱导配体（TRAIL）死亡受体，并诱导癌细胞凋亡。姜黄烯是一种倍半萜，能够穿透蛋白质的疏水口袋，对多种蛋白质发挥其抑制活性。我们发现它与肿瘤坏死因子、激酶κB（IKKβ）以及肿瘤坏死因子信号通路中的核因子κB（NF-κB）组成蛋白有良好的结合。我们的结果表明，姜黄烯可以通过抑制细胞质蛋白发挥其凋亡活性。它抑制激活NF-κB的IKKβ激酶，并且还与肿瘤坏死因子信号通路中的NF-κB复合物结合。阻断这两种蛋白可导致细胞增殖蛋白的抑制以及可能最终诱导细胞凋亡。
