Leelawat Surang, Leelawat Kawin
Faculty of Pharmacy, Rangsit University, Amphoe Mueang, Pathum Thani 12000, Thailand.
Department of Surgery, Rajavithi Hospital, Bangkok 10400, Thailand.
Oncol Lett. 2017 Feb;13(2):961-966. doi: 10.3892/ol.2016.5488. Epub 2016 Dec 12.
Cholangiocarcinoma (CCA) is one of the most common causes of cancer-associated mortality in Thailand. Certain phytochemicals have been demonstrated to modulate apoptotic signaling pathways, which may be targeted for the prevention and treatment of cancer. Therefore, the aim of the present study was to investigate the effect of specific medicinal plants on the inhibition of CCA cell proliferation, and to identify the molecular mechanisms underlying this. A WST-1 cell proliferation assay was performed using an RMCCA1 cell line, and apoptotic signaling pathways were also investigated using a PathScan Stress and Apoptosis Signaling Antibody Array Kit. The cell proliferation assay indicated that extracts from the fruit pulp (PEf), seed (PEs), fruit pulp (TCf), seed (TCs), seed (ACs), (CL) and seed (MOs) exerted anti-proliferative activity in RMCCA1 cells. In addition, the PathScan assay revealed that certain pro-apoptotic molecules, including caspase-3, poly (ADP-ribose) polymerase, checkpoint kinase 2 and tumor protein 53, exhibited increased activity in RMCCA1 cells treated with the aforementioned selected plant extracts, with the exception of PEf. The mitogen-activated protein kinase (MAPK) pathways (including ERK1/2 and p38 MAPK) expression level was significantly increased in RMCCA1 cells pre-treated with extracts of PEs, TCf, CL and MOs. The activation of protein kinase B (Akt) was significantly demonstrated in RMCCA1 cells pre-treated with extracts of TCf, ACs and MOs. In summary, the present study demonstrated that extracts of PEs, TCf, TCs, ACs, CL and MOs exhibited anti-proliferative effects in CCA cells by inducing pro-apoptotic signals and modulating signal transduction molecules. Further studies are required to demonstrate the potential applications of specific plant extracts for the treatment of human cancer.
胆管癌（CCA）是泰国癌症相关死亡的最常见原因之一。某些植物化学物质已被证明可调节凋亡信号通路，这可能成为癌症预防和治疗的靶点。因此，本研究的目的是研究特定药用植物对CCA细胞增殖抑制的影响，并确定其潜在的分子机制。使用RMCCA1细胞系进行WST-1细胞增殖测定，并使用PathScan应激和凋亡信号抗体阵列试剂盒研究凋亡信号通路。细胞增殖测定表明，果肉（PEf）、种子（PEs）、果肉（TCf）、种子（TCs）、种子（ACs）、（CL）和种子（MOs）的提取物对RMCCA1细胞具有抗增殖活性。此外，PathScan测定显示，某些促凋亡分子，包括半胱天冬酶-3、聚（ADP-核糖）聚合酶、检查点激酶2和肿瘤蛋白53，在用上述选定植物提取物处理的RMCCA1细胞中活性增加，但PEf除外。在用PEs、TCf、CL和MOs提取物预处理的RMCCA1细胞中，丝裂原活化蛋白激酶（MAPK）通路（包括ERK1/2和p38 MAPK）的表达水平显著增加。在用TCf、ACs和MOs提取物预处理的RMCCA1细胞中，蛋白激酶B（Akt）的活化得到显著证实。总之，本研究表明，PEs、TCf、TCs、ACs、CL和MOs的提取物通过诱导促凋亡信号和调节信号转导分子，对CCA细胞具有抗增殖作用。需要进一步研究来证明特定植物提取物在治疗人类癌症方面的潜在应用。
