Polygonatum cyrtonema lectin induces murine fibrosarcoma L929 cell apoptosis and autophagy via blocking Ras-Raf and PI3K-Akt signaling pathways.
Polygonatum cyrtonema lectin (PCL), a mannose/sialic acid-binding lectin, has been reported to display remarkable anti-proliferative and apoptosis-inducing activities toward a variety of cancer cells; however, the precise molecular mechanisms by which PCL induces cancer cell death are still elusive. In the current study, we found that PCL could induce apoptosis and autophagy in murine fibrosarcoma L929 cells. Subsequently, we demonstrated that inhibition of Ras could promote L929 cell death, suggesting that Ras-Raf signaling pathway plays the key negative regulator in PCL-induced apoptosis. And, we showed that Ras-Raf signaling pathway was also involved in PCL-induced autophagy as the negative regulator. In addition, we found that class I phosphatidylinositol 3-kinase (PI3K)-Akt signaling pathway could play the negative regulator in PCL-induced apoptosis and autophagy. Taken together, these results demonstrate that PCL induces murine fibrosarcoma L929 cell apoptosis and autophagy via blocking Ras-Raf and PI3K-Akt signaling pathways.
Liu
Bo
B
School of Life Sciences & State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610064, China. liubo2400@163.com
Wu
Jin-ming
JM
Li
Jing
J
Liu
Jun-jie
JJ
Li
Wen-wen
WW
Li
Chun-yang
CY
Xu
Huai-long
HL
Bao
Jin-ku
JK
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005354:Fibrosarcoma / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D006576:Heterocyclic Compounds, 4 or More Rings / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D051379:Mice; D046529:Microscopy, Electron, Transmission; D010636:Phenols / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D037121:Plant Lectins / Q000494:pharmacology*; D011090:Polyenes / Q000494:pharmacology; D031384:Polygonatum / Q000378:metabolism; D053284:Polyunsaturated Alkamides / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013777:Tetrazoles / Q000494:pharmacology; D013997:Time Factors; D000077191:Wortmannin; D048490:raf Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D018631:ras Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism
D000730:Androstadienes; D006576:Heterocyclic Compounds, 4 or More Rings; D007211:Indoles; D010636:Phenols; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D037121:Plant Lectins; D011090:Polyenes; D053284:Polyunsaturated Alkamides; D051057:Proto-Oncogene Proteins c-akt; D013777:Tetrazoles; D000077191:Wortmannin; D048490:raf Kinases; D018631:ras Proteins; C501199:KP372-1; C054474:manumycin; C489251:5-iodo-3-((3,5-dibromo-4-hydroxyphenyl)methylene)-2-indolinone