Andas A Reenaa Joys, Abdul Ahmad Bustamam, Rahman Heshu Sulaiman, Sukari Mohd Aspollah, Abdelwahab Siddig Ibrahim, Samad Nozlena Abdul, Anasamy Theebaa, Arbab Ismail Adam
UPM-MAKNA Cancer Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, Serdang, Malaysia E-mail :
Asian Pac J Cancer Prev. 2015;16(10):4311-6. doi: 10.7314/apjcp.2015.16.10.4311.
Hepatocellular carcinoma (HCC) is a primary liver cancer with high global incidence and mortality rates. Current candidate drugs to treat HCC remain lacking and those in use possess undesirable side effects. In this investigation, the antiproliferative effects of dentatin (DTN), a natural coumarin, were evaluated on HepG2 cells and DTN's probable preliminary molecular mechanisms in apoptosis induction were further investigated. DTN significantly (p<0.05) suppressed proliferation of HepG2 cells with an IC50 value of 12.0 μg/mL, without affecting human normal liver cells, WRL-68 (IC50>50 μg/mL) causing G0/G1 cell cycle arrest via apoptosis induction. Caspase colorimetric assays showed markedly increased levels of caspase-3 and caspase-9 activities throughout the treatment period. Western blotting of treated HepG2 cells revealed inhibition of NF-κB that triggers the mitochondrial-mediated apoptotic signaling pathway by up-regulating cytoplasmic cytochrome c and Bax, and down-regulating Bcl-2 and Bcl-xL. The current findings suggest DTN has the potential to be developed further as an anticancer compound targeting human HCC.
肝细胞癌（HCC）是一种在全球发病率和死亡率都很高的原发性肝癌。目前治疗HCC的候选药物仍然匮乏，且现有药物存在不良副作用。在本研究中，评估了天然香豆素齿孔酸（DTN）对HepG2细胞的抗增殖作用，并进一步研究了DTN诱导细胞凋亡的可能初步分子机制。DTN显著（p<0.05）抑制HepG2细胞的增殖，IC50值为12.0μg/mL，且不影响人正常肝细胞WRL-68（IC50>50μg/mL），通过诱导凋亡导致G0/G1期细胞周期阻滞。半胱天冬酶比色法显示在整个治疗期间，半胱天冬酶-3和半胱天冬酶-9的活性水平显著增加。对处理后的HepG2细胞进行蛋白质免疫印迹分析显示，NF-κB受到抑制，NF-κB通过上调细胞质细胞色素c和Bax以及下调Bcl-2和Bcl-xL来触发线粒体介导的凋亡信号通路。目前的研究结果表明，DTN有潜力进一步开发成为一种针对人类HCC的抗癌化合物。
