Qi Fei, Yan Qiang, Zheng Zhaozheng, Liu Jian, Chen Yan, Zhang Guiyang
Department of Anorectal Surgery, Huzhou Central Hospital, Huzhou, Zhejiang 313000, China.
J BUON. 2018 Mar-Apr;23(2):346-352.
Colon cancer ranks second in mortality among all human malignancies, creating thus a need for exploration of novel molecules that would prove effective, cost-effective and with lower toxicity. In the recent past monoterpenes have gained tremendous attention for their anticancer activity. In the present study we evaluated the anticancer effects of two important monoterpenes, geraniol and geranyl acetate against colo-205 cancer cells.
The antiproliferative activity was determined by MTT assay. Apoptosis was assessed by DAPI staining and DNA damage was checked by comet assay. The cell cycle analysis was carried out by flow cytometry and protein expression was examined by western blotting.
The results showed that both geraniol and geranyl acetate exhibited significant anticancer activity against colo-205 cancer cell line with IC50 values of 20 and 30 μM respectively. To find out the underlying mechanism, DAPI staining was carried out and it was observed that both the monoterpenes, geraniol and geranyl acetate, induced apoptosis in colo-205 cells. The apoptosis was also associated with upregulation of Bax and downregulation of Bcl-2 expressions, indicative of mitochondrial apoptosis. Moreover, these two monoterpenes could trigger DNA damage and G2/M cell cycle arrest in colo-205 cells.
Taken together, we propose that geraniol and geranyl acetate may prove to be important lead molecular candidates for the treatment of colon cancer. Their anticancer activity can be attributed to the ability to trigger apoptosis, DNA damage and cell cycle arrest.
在所有人类恶性肿瘤中，结肠癌的死亡率位居第二，因此需要探索新型分子，这些分子应被证明有效、具有成本效益且毒性较低。最近，单萜因其抗癌活性而备受关注。在本研究中，我们评估了两种重要的单萜香叶醇和乙酸香叶酯对colo - 205癌细胞的抗癌作用。
通过MTT法测定细胞增殖活性。通过DAPI染色评估细胞凋亡，并通过彗星试验检查DNA损伤。通过流式细胞术进行细胞周期分析，并通过蛋白质印迹法检测蛋白质表达。
结果表明，香叶醇和乙酸香叶酯对colo - 205癌细胞系均表现出显著的抗癌活性，IC50值分别为20和30 μM。为了找出潜在机制，进行了DAPI染色，观察到香叶醇和乙酸香叶酯这两种单萜均能诱导colo - 205细胞凋亡。细胞凋亡还与Bax表达上调和Bcl - 2表达下调有关，表明存在线粒体凋亡。此外，这两种单萜可引发colo - 205细胞的DNA损伤和G2/M期细胞周期阻滞。
综上所述，我们认为香叶醇和乙酸香叶酯可能是治疗结肠癌的重要潜在分子候选物。它们的抗癌活性可归因于触发细胞凋亡、DNA损伤和细胞周期阻滞的能力。
