Mai Chun Wai, Yaeghoobi Marzieh, Abd-Rahman Noorsaadah, Kang Yew Beng, Pichika Mallikarjuna Rao
Department of Pharmaceutical Chemistry, School of Pharmacy, International Medical University, 126, Jalan Jalil Perkasa 19, Bukit Jalil, 57000 Kuala Lumpur, Malaysia.
Drug Design and Development Research Group, Department of Chemistry, University of Malaya, Kuala Lumpur, Malaysia.
Eur J Med Chem. 2014 Apr 22;77:378-87. doi: 10.1016/j.ejmech.2014.03.002. Epub 2014 Mar 3.
In the present study, a series of 46 chalcones were synthesised and evaluated for antiproliferative activities against the human TRAIL-resistant breast (MCF-7, MDA-MB-231), cervical (HeLa), ovarian (Caov-3), lung (A549), liver (HepG2), colorectal (HT-29), nasopharyngeal (CNE-1), erythromyeloblastoid (K-562) and T-lymphoblastoid (CEM-SS) cancer cells. The chalcone 38 containing an amino (-NH2) group on ring A was the most potent and selective against cancer cells. The effects of the chalcone 38 on regulation of 43 apoptosis-related markers in HT-29 cells were determined. The results showed that 20 apoptotic markers (Bad, Bax, Bcl-2, Bcl-w, Bid, Bim, CD40, Fas, HSP27, IGF-1, IGFBP-4, IGFBP-5, Livin, p21, Survivin, sTNF-R2, TRAIL-R2, XIAP, caspase-3 and caspase-8) were either up regulated or down regulated.
在本研究中，合成了一系列46种查尔酮，并评估了它们对人TRAIL抗性乳腺癌（MCF-7、MDA-MB-231）、宫颈癌（HeLa）、卵巢癌（Caov-3）、肺癌（A549）、肝癌（HepG2）、结直肠癌（HT-29）、鼻咽癌（CNE-1）、红白血病（K-562）和T淋巴母细胞癌（CEM-SS）细胞的抗增殖活性。在A环上含有氨基（-NH2）的查尔酮38对癌细胞最有效且具有选择性。测定了查尔酮38对HT-29细胞中43种凋亡相关标志物调节的影响。结果显示，20种凋亡标志物（Bad、Bax、Bcl-2、Bcl-w、Bid、Bim、CD40、Fas、HSP27、IGF-1、IGFBP-4、IGFBP-5、Livin、p21、Survivin、sTNF-R2、TRAIL-R2、XIAP、caspase-3和caspase-8）的表达上调或下调。
