Anticancer effects of pure amygdalin, bitter and sweet apricot kernel extract (Prunus armeniaca L.) on pancreatic cancer cells

Abstract

Introduction: Pancreatic cancer is the fourth common cause of cancer death. Surgery and chemotherapy are the common treatment strategies for pancreatic cancer; however, the response rate is less than 20% at advance stages. In recent years, growing interest has been dedicated to natural products. Apricot (Prunus armeniaca L.) kernel possesses a number of pharmacological properties including antitumor activity and amygdalin from apricot kernel can induce apoptosis. In this study cytotoxic and apoptotic effects of amygdalin and bitter/ sweet apricot kernel ethanolic extract on human pancreatic cancer PANC-1 and normal epithelial 293/KDR cells were investigated. Material and methods: The extracts were prepared by maceration. MTT assay was performed for cytotoxicity assessment. Apoptosis of treated PANC-1 and 293/KDR cells was detected by DAPI staining and flow cytometry and the expression of pro-apoptotic (Bax and caspase-3) and anti-apoptotic (Bcl-2) genes was evaluated by Real-time PCR analysis. Results: Both bitter/ sweet apricot kernel ethanolic extracts and amygdalin inhibited pancreatic cancer cells growth in a dose- and time-dependent manner. The IC-50 values of bitter and sweet apricot kernel ethanolic extracts were 704 and 945 µg/mL and amygdalin was 35 mg/mL at 72 h, respectively. According to data from MTT assay, bitter apricot kernel ethanolic extract was more cytotoxic than sweet apricot kernel ethanolic extract and amygdalin in suppressing PANC-1 cells growth. DAPI staining and flow cytometric analysis revealed fragmented and condensed nuclei and elevated numbers of early and late stage apoptotic cells, respectively. Also, upregulation of Bax and caspase-3 and downregulation of Bcl-2 gene expression confirmed apoptosis in PANC-1 cells. These results indicated that treatments of amygdalin and bitter/ sweet apricot kernel ethanolic extracts could mediate apoptosis induction in PANC-1 pancreatic cancer cells through a mitochondrial dependent pathway. Conclusion: These findings suggest that amygdalin and bitter/ sweet apricot kernel ethanolic extract function as a potent pro-apoptotic factor for human pancreatic cancer cells without significant effect on 293/KDR cells and bitter apricot kernel ethanolic extract have the most significant effect on growth inhibition and apoptosis induction on pancreatic cancer cells. Therefore, the potent anti-cancer components of bitter apricot kernel ethanolic extract should be further identified. Furthermore, in vivo investigations are required to confirm bitter and sweet apricot kernel ethanolic extract’s clinical value as an anti-tumor drug.