Jian Yang1, Ying Liu2, Shengnan Lu3, Xuejia Sun4, Yue Yin5, Kaifeng Wang6, Shi Liu7. 1. Department of General Surgery, The First Affiliated Hospital, Jiamusi University, 154003, Jiamusi, Heilongjiang Province, China. 2. Department of Medical Oncology, The Third Affiliated Hospital, Qiqihar Medical University, 161099, Qiqihar, Heilongjiang Province, China. 3. Department of Ultrasound, The Third Affiliated Hospital, Qiqihar Medical University, 161099, Qiqihar, Heilongjiang Province, China. 4. Department of Radiology, The Third Affiliated Hospital, Qiqihar Medical University, 161099, Qiqihar, Heilongjiang Province, China. 5. Department of Science and Education, The Third Affiliated Hospital, Qiqihar Medical University, 161099, Qiqihar, Heilongjiang Province, China. 6. Department of Vascular surgery, The First Affiliated Hospital, Jiamusi University, 154003, Jiamusi, Heilongjiang Province, China. 7. Central Laboratory, The Third Affiliated Hospital, Qiqihar Medical University, 27 Taishun Street, Tiefeng District, 161099, Qiqihar, Heilongjiang Province, China. shiliu2199@163.com.
Abstract
BACKGROUND: Coix seed oil (CSO) has a wide range of anticancer effects. However, the mechanism of action against pancreatic cancer (PC) and regulation of mitochondria in vitro is still unclear. MATERIALS AND RESULTS: This research investigated the possible mechanism of CSO induction of PC cell apoptosis and regulating mitochondrial functional damage. Proliferation of PC cells, mitochondrial membrane potential (MMP), qualitative and quantitative analysis of PC cell apoptosis, openness of mitochondrial permeability transition pore, related protein expression, generation of reactive oxygen species (ROS), and gene expression were determined by cell counting kit-8, JC-1 staining, acridine orange and ethidium bromide staining, flow cytometry, calcein-AM/cobalt staining, western blotting, dichlorofluorescein diacetate probe, and quantitative real-time reverse transcription-polymerase chain reaction, respectively. We confirmed that PTEN protein was involved in CSO-induced PANC-1 cell apoptosis and mitochondrial functional damage. CSO induced depolarization of MMP, increased opening of the mitochondrial permeability transition pore, increased ROS production, and further increased mitochondrial damage. Additionally, CSO downregulated expression of p-AKT and p-PI3K proteins; upregulated protein expression of cleaved caspase-9, Bax, cleaved caspase-3 and cytochrome c; and downregulated expression of Bcl-2 by upregulating the PTEN gene. The corresponding protein expression was consistent with the gene expression level. Furthermore, the loss of function of PTEN protein reduces the ability of CSO to induce apoptosis of PANC-1 cells and damage to mitochondrial function. CONCLUSIONS: CSO induces apoptosis of PANC-1 PC cells by modulating mitochondrial functional impairment and related apoptotic molecules via PTEN, which may be closely related to the PI3K/AKT signaling pathway.
BACKGROUND: Coix seed oil (CSO) has a wide range of anticancer effects. However, the mechanism of action against pancreatic cancer (PC) and regulation of mitochondria in vitro is still unclear. MATERIALS AND RESULTS: This research investigated the possible mechanism of CSO induction of PC cell apoptosis and regulating mitochondrial functional damage. Proliferation of PC cells, mitochondrial membrane potential (MMP), qualitative and quantitative analysis of PC cell apoptosis, openness of mitochondrial permeability transition pore, related protein expression, generation of reactive oxygen species (ROS), and gene expression were determined by cell counting kit-8, JC-1 staining, acridine orange and ethidium bromide staining, flow cytometry, calcein-AM/cobalt staining, western blotting, dichlorofluorescein diacetate probe, and quantitative real-time reverse transcription-polymerase chain reaction, respectively. We confirmed that PTEN protein was involved in CSO-induced PANC-1 cell apoptosis and mitochondrial functional damage. CSO induced depolarization of MMP, increased opening of the mitochondrial permeability transition pore, increased ROS production, and further increased mitochondrial damage. Additionally, CSO downregulated expression of p-AKT and p-PI3K proteins; upregulated protein expression of cleaved caspase-9, Bax, cleaved caspase-3 and cytochrome c; and downregulated expression of Bcl-2 by upregulating the PTEN gene. The corresponding protein expression was consistent with the gene expression level. Furthermore, the loss of function of PTEN protein reduces the ability of CSO to induce apoptosis of PANC-1 cells and damage to mitochondrial function. CONCLUSIONS: CSO induces apoptosis of PANC-1 PC cells by modulating mitochondrial functional impairment and related apoptotic molecules via PTEN, which may be closely related to the PI3K/AKT signaling pathway.
Authors: Yi-Ping Zhan; Xin-En Huang; Jie Cao; Yan-Yan Lu; Xue-Yan Wu; Jin Liu; Xia Xu; Jin Xiang; Li-Hong Ye Journal: Asian Pac J Cancer Prev Date: 2012
Authors: Safieh Ebrahimi; Mina Hosseini; Soodabeh Shahidsales; Mina Maftouh; Gordon A Ferns; Majid Ghayour-Mobarhan; Seyed Mahdi Hassanian; Amir Avan Journal: Curr Med Chem Date: 2017 Impact factor: 4.530
Authors: Marco Falasca; Federico Selvaggi; Richard Buus; Sara Sulpizio; Charlotte E Edling Journal: Anticancer Agents Med Chem Date: 2011-06 Impact factor: 2.505
Authors: Haotian Yang; Rehan M Villani; Haolu Wang; Matthew J Simpson; Michael S Roberts; Min Tang; Xiaowen Liang Journal: J Exp Clin Cancer Res Date: 2018-11-01