Department of Clinical Nutrition, School of Nutrition and Food Sciences, Tabriz University of Medical Science, Tabriz, Iran.
Research Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran.
Mol Biol Rep. 2020 Mar;47(3):1895-1904. doi: 10.1007/s11033-020-05286-w. Epub 2020 Feb 5.
Pancreatic cancer is the fourth common cause of cancer death. Surgery and chemotherapy are the common treatment strategies for pancreatic cancer patients; however, the response rate is less than 20% at advanced stages. In recent years, growing interest has been dedicated to natural products. Bitter apricot seeds possess a number of pharmacological properties including antitumor activity and amygdalin from bitter apricot seeds can induce apoptosis. In this study, we investigated the cyto/genotoxic effects of bitter apricot ethanolic extract (BAEE) and amygdalin on human pancreatic cancer PANC-1 and normal epithelial 293/KDR cells. BAEE was assessed using high-performance liquid chromatography for the confirmation of the structure. The biological impacts of BAEE and amygdalin on PANC-1 and 293/KDR cells were evaluated by MTT assay, DAPI staining, AnnexinV/PI and Real-time qPCR analysis. BAEE and amygdalin inhibited cancer cell growth in a dose- and time-dependent manner. DAPI staining and flow cytometric analysis revealed fragmented nuclei and elevated numbers of early and late apoptotic cells, respectively. Also, increased Bax/Bcl-2 ratio and upregulation of caspase-3 further confirmed the occurrence of apoptosis in PANC-1 cells, but not in non-cancerous 293/KDR cells. These results indicate that BAEE could mediate apoptosis induction in cancer cells through a mitochondria dependent pathway. These findings suggest that BAEE functions as a potent pro-apoptotic factor for human pancreatic cancer cells without a significant effect on 293/KDR cells. Though, the potent anti-cancer components of BAEE should be further identified. Moreover, in vivo investigations are required to confirm bitter apricot ethanolic extract's clinical value as an anti-tumor drug.
胰腺癌是癌症死亡的第四大常见原因。手术和化疗是胰腺癌患者的常见治疗策略;然而,晚期患者的响应率低于 20%。近年来,人们对天然产物越来越感兴趣。苦杏仁种子具有多种药理特性,包括抗肿瘤活性,苦杏仁中的苦杏仁苷可以诱导细胞凋亡。在这项研究中,我们研究了苦杏仁乙醇提取物(BAEE)和苦杏仁苷对人胰腺癌细胞 PANC-1 和正常上皮 293/KDR 细胞的细胞毒性/遗传毒性作用。使用高效液相色谱法评估 BAEE 以确认其结构。通过 MTT 测定、DAPI 染色、AnnexinV/PI 和实时 qPCR 分析评估 BAEE 和苦杏仁苷对 PANC-1 和 293/KDR 细胞的生物学影响。BAEE 和苦杏仁苷以剂量和时间依赖的方式抑制癌细胞生长。DAPI 染色和流式细胞术分析显示碎片化的细胞核和早期和晚期凋亡细胞的数量增加。此外,Bax/Bcl-2 比值增加和 caspase-3 的上调进一步证实了 PANC-1 细胞中细胞凋亡的发生,但在非癌细胞 293/KDR 细胞中没有。这些结果表明,BAEE 可以通过线粒体依赖性途径介导癌细胞凋亡。这些发现表明,BAEE 作为一种有效的促凋亡因子,对人胰腺癌细胞具有作用,而对 293/KDR 细胞没有明显作用。尽管如此,BAEE 的有效抗癌成分仍需进一步鉴定。此外,需要进行体内研究来确认苦杏仁乙醇提取物作为抗肿瘤药物的临床价值。