title: Momordin Ic couples apoptosis with autophagy in human hepatoblastoma cancer cells by reactive oxygen species (ROS)-mediated PI3K/Akt and MAPK signaling pathways.
abstract: Momordin Ic is a principal saponin constituent of Fructus Kochiae, which acts as an edible and pharmaceutical product more than 2000 years in China. Our previous research found momordin Ic induced apoptosis by PI3K/Akt and MAPK signaling pathways in HepG2 cells. While the role of autophagy in momordin Ic induced cell death has not been discussed, and the connection between the apoptosis and autophagy is not clear yet. In this work, we reported momordin Ic promoted the formation of autophagic vacuole and expression of Beclin 1 and LC-3 in a dose- and time-dependent manner. Compared with momordin Ic treatment alone, the autophagy inhibitor 3-methyladenine (3-MA) also can inhibit apoptosis, while autophagy activator rapamycin (RAP) has the opposite effect, and the apoptosis inhibitor ZVAD-fmk also inhibited autophagy induced by momordin Ic. Momordin Ic simultaneously induces autophagy and apoptosis by suppressing the ROS-mediated PI3K/Akt and activating the ROS-related JNK and P38 pathways. Additionally, momordin Ic induces apoptosis by suppressing PI3K/Akt-dependent NF-κB pathways and promotes autophagy by ROS-mediated Erk signaling pathway. Those results suggest that momordin Ic has great potential as a nutritional preventive strategy in cancer therapy.
authors.affiliation: College of Food Science and Engineering, Northwest A&F University, 28, Xi-nong Road, Yangling 712100, China.
authors.forename: Yashi
authors.initials: Y
authors.lastname: Mi
authors.affiliation: College of Food Science and Engineering, Northwest A&F University, 28, Xi-nong Road, Yangling 712100, China.
authors.forename: Chunxia
authors.initials: C
authors.lastname: Xiao
authors.affiliation: Functional Food Engineering and Technology Research Center of Shaanxi Province, Xian 710054, China.
authors.forename: Qingwei
authors.initials: Q
authors.lastname: Du
authors.affiliation: College of Food Science and Engineering, Northwest A&F University, 28, Xi-nong Road, Yangling 712100, China.
authors.forename: Wanqiang
authors.initials: W
authors.lastname: Wu
authors.affiliation: College of Food Science and Engineering, Northwest A&F University, 28, Xi-nong Road, Yangling 712100, China.
authors.forename: Guoyuan
authors.initials: G
authors.lastname: Qi
authors.affiliation: College of Food Science and Engineering, Northwest A&F University, 28, Xi-nong Road, Yangling 712100, China. Electronic address: xueboliu@aliyun.com.
authors.forename: Xuebo
authors.initials: X
authors.lastname: Liu
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D056945:Hep G2 Cells; D018197:Hepatoblastoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000502:physiology*; D016328:NF-kappa B / Q000502:physiology; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D016328:NF-kappa B; D017382:Reactive Oxygen Species; C408362:momordin I (Oleanolic Acid); D009828:Oleanolic Acid; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt
keywords: Apoptosis; Autophagy; Crosstalk; HepG2 cells; Momordin Ic