title: Cucurmosin induces apoptosis of BxPC-3 human pancreatic cancer cells             via inactivation of the EGFR signaling pathway.
abstract: Pancreatic cancer remains the fourth most common cause of cancer-related             death in the United States. Potent therapeutic strategies are urgently needed             for pancreatic cancer. Cucurmosin is a novel type 1 ribosome-inactivating protein             (RIP) isolated from the sarcocarp of Cucurbita moschata (pumpkin). Due to its             cytotoxicity, cucurmosin can inhibit tumor cell proliferation through induction             of apoptosis on tumor cells, but the specific mechanism is still unclear. We explored             the function of cucurmosin in BxPC-3 pancreatic cancer cells using multiple cellular             and molecular approaches such as 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium             bromide assay, flow cytometry, reverse transcription polymerase chain reaction             (RT-PCR), Western blotting and transmission electron microscopy for observing             typical changes and formation of apoptotic bodies. We found that cucurmosin inhibited             the proliferation of BxPC-3 cells in a time- and dose-dependent manner, and increased             the cell population in the G0-G1 phase. With increasing concentration of cucurmosin,             the expression of EGFR, p-PI3K, Akt, p-Akt, mTOR, p-mTOR, P70S6K-α, p-P70S6K-α,             4E-BP1 and p-4E-BP1 at the protein level was decreased, whereas the expression             of p-Bad and caspase-9 was elevated. However, the mRNA expression of EGFR did             not change. These findings suggest that cucurmosin can down-regulate the expression             of EGFR by targeting. Cucurmosin induces the apoptosis of BxPC-3 pancreatic cancer             cells via the PI3K/Akt/mTOR signaling pathway.
authors.affiliation: Department of General Surgery, Union XieHe Hospital, and Department of Pharmacology, Fujian Medical University, Fuzhou, Fujian Province, PR China.
authors.forename: Baoming
authors.initials: B
authors.lastname: Zhang
authors.forename: Heguang
authors.initials: H
authors.lastname: Huang
authors.forename: Jieming
authors.initials: J
authors.lastname: Xie
authors.forename: Chunsen
authors.initials: C
authors.lastname: Xu
authors.forename: Minghuang
authors.initials: M
authors.lastname: Chen
authors.forename: Congfei
authors.initials: C
authors.lastname: Wang
authors.forename: Aiqin
authors.initials: A
authors.lastname: Yang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Yin
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism*; D016193:G1 Phase / Q000187:drug effects / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics; D006801:Humans; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D010940:Plant Proteins / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics; D016192:Resting Phase, Cell Cycle / Q000187:drug effects / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects*; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D066246:ErbB Receptors; D019869:Phosphatidylinositol 3-Kinases; D010940:Plant Proteins; D051057:Proto-Oncogene Proteins c-akt; D012333:RNA, Messenger; D058570:TOR Serine-Threonine Kinases; C412450:cucurmosin protein, Cucurbita moschata; C546842:MTOR protein, human; C512478:EGFR protein, human