Weerapreeyakul Natthida, Machana Sasipawan, Barusrux Sahapat
Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen, 40002 Thailand.
Graduate School, Khon Kaen University, Khon Kaen, 40002 Thailand.
Chin Med. 2016 Jun 29;11:29. doi: 10.1186/s13020-016-0103-z. eCollection 2016.
This study aims to determine the synergistic effects of the chemotherapeutic drug melphalan and the phytoconstituents extracted from Pinus kesiya Royle ex Gordon (Simaosong) in human cancer cells.
P. kesiya twigs extracted from 50 % ethanol-water were evaluated alone (6-500 µg/mL) and in combination with melphalan (0.75-15 µg/mL). The cytotoxic effects of single extract or extract and melphalan combination were examined by a neutral red assay to investigate their antiproliferative and apoptosis induction effects in the U937 and HepG2 cell lines. Nuclei morphological change and DNA fragmentation were examined by DNA nuclei staining with 4´6-diamidino-2-phenylindole (DAPI) and agarose gel electrophoresis, respectively. The chemical constituents of the P. kesiya extract were assessed using gas chromatography-mass spectrometry (GC-MS) analysis. The synergistic effects of different IC50 ratios of the P. kesiya extract and melphalan combination were analyzed in each cancer cell line. The dose reduction index (DRI) was calculated to determine the extent of concentration reduction in the combination treatment compared with the concentration of each single treatment.
The IC50 ratios for melphalan to P. kesiya extract that caused 75 % antiproliferation could be reduced after combination. This response was greater in the U937 cells than in the HepG2 cells (all P < 0.001). Melphalan and P. kesiya extract had a similar effect on apoptosis induction both singly and in combination. P. kesiya extract synergized the antiproliferation and apoptosis induction effects of melphalan.
Combining the P. kesiya extract with melphalan reduced toxicity while retaining the therapeutic efficacy of melphalan.
本研究旨在确定化疗药物美法仑与从思茅松（Pinus kesiya Royle ex Gordon）中提取的植物成分在人癌细胞中的协同作用。
对用50%乙醇 - 水提取的思茅松嫩枝单独（6 - 500μg/mL）以及与美法仑（0.75 - 15μg/mL）联合进行评估。通过中性红试验检测单一提取物或提取物与美法仑组合的细胞毒性作用，以研究它们在U937和HepG2细胞系中的抗增殖和诱导凋亡作用。分别通过用4,6 - 二脒基 - 2 - 苯基吲哚（DAPI）进行DNA细胞核染色和琼脂糖凝胶电泳检测细胞核形态变化和DNA片段化。使用气相色谱 - 质谱（GC - MS）分析评估思茅松提取物的化学成分。分析思茅松提取物与美法仑组合不同IC50比例在每个癌细胞系中的协同作用。计算剂量降低指数（DRI）以确定联合治疗与每种单一治疗浓度相比浓度降低的程度。
联合后可降低导致75%抗增殖的美法仑与思茅松提取物的IC50比例。这种反应在U937细胞中比在HepG2细胞中更大（所有P < 0.001）。美法仑和思茅松提取物单独及联合使用时对诱导凋亡具有相似作用。思茅松提取物增强了美法仑的抗增殖和诱导凋亡作用。
将思茅松提取物与美法仑联合使用可降低毒性，同时保留美法仑的治疗效果。
