Two methylene groups in phospholipids distinguish between apoptosis and necrosis for tumor cells

Nagami, Hideaki; Nakano, Koji; Ichihara, Hideaki; Matsumoto, Yōko; Ueoka, Ryuichi

doi:10.1016/j.bmcl.2005.11.034

Cited by 20 publications

(8 citation statements)

References 13 publications

(14 reference statements)

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“…It was found that the hybrid liposomes composed of phospholipids dilauroylphosphatidylcholine (DLPC), dimyristoylphosphatidylcholine (DMPC), and dipalmitoylphosphatidylchoine (DPPC) cause necrosis, apoptosis, and no changes, respectively. 34) Although both necrosis and apoptosis result in deaths of cells, necrosis is toxic and only apoptosis is a desired phenomenon for the organisms. The differences in these three phospholipids are just the lengths of the hydrophobic alkyl chains; DLPC, DMPC, and DPPC have 12, 14, and 16 carbon atoms after glycerol.…”

Section: Discussionmentioning

confidence: 99%

Phase Behavior of a Lipid Bilayer System Studied by a Replica-Exchange Molecular Dynamics Simulation

2012

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A replica-exchange molecular dynamics (REMD) simulation of a lipid bilayer system has been performed in order to study the sol-gel phase transitions. The REMD method enhances conformational sampling efficiency, and one can study the system in a wide temperature range at once. A coarse-grained model MARTINI was used. The results show sudden changes in enthalpy, bilayer thickness, and area of bilayer around 296 K. A peak in heat capacity was also observed around this temperature. These results suggest sol-gel phase transitions. We also investigated temperature dependences of composite energy terms. According to potential of mean force maps and tilt angle distributions, the bilayer is found to have two states in the gel phase. One is a tilted gel state and the other is an un-tilted gel state. A previous work with MARTINI force field reported only the un-titled gel state. Another previous work with MARTINI force field reported titled gel state only with externally applied tension. This suggests that enhanced conformational sampling is important even with a coarse-grained model which has smoother energy landscapes and reach longer time scales than atomistic models. The lipid bilayer in the un-tilted gel state is a little thicker than that in the tilted gel state, while the area of the lipid bilayer is quite similar. Tilt angle distributions are also analyzed, and the tilt angle of the tilted gel phase is around 30 .

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Section: Discussionmentioning

confidence: 99%

Phase Behavior of a Lipid Bilayer System Studied by a Replica-Exchange Molecular Dynamics Simulation

2012

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“…Neither apoptosis nor necrosis was observed for HLs of 90 mol% DPPC/10 mol% C 12 (EO) 23 . Thus, two methylene groups of acyl chains in phosphatidylcholines could distinguish between apoptosis, and necrosis has already been reported (Nagami et al, 2006b).…”

Section: Discussionmentioning

confidence: 75%

“…Magnification: Â400. Morphological change in human promyelocytic leukemia (HL-60) cells after the treatment with HLs composed of phospholipids having the same hydrophilic head group (phosphatidylcholine group) and different hydrophobic alkyl chains (L--dilauroylphosphatidylcholine, C12: DLPC; C14: DMPC; L--dipalmitoylphosphatidylcholine, C16: DPPC) and C 12 (EO) 23 using a time-laps video has been investigated (Nagami et al, 2006b). The formation of bleb and corpuscle indicating the characteristic feature of apoptosis was observed for HLs of 90 mol% DMPC/10 mol% C 12 (EO) 23 .…”

Section: Discussionmentioning

confidence: 99%

Therapeutic effects of hybrid liposomes without drugs for rheumatoid arthritis

et al. 2013

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Hybrid liposomes (HLs) can be prepared by simply sonicating a mixture of vesicular and micellar molecules in buffer solutions. This study aims to demonstrate inhibitory effects of HLs on the growth of fibroblast-like synoviocytes along with apoptosis and therapeutic effects of HLs in a mouse model with rheumatoid arthritis (RA). HLs composed of 95 mol% L-α-dimyristoylphosphatidylcholine (DMPC) and 5 mol% polyoxyethylene(23)dodecyl ether (C12(EO)23) were prepared by the sonication method. The inhibitory effects of HLs on the growth of human fibroblast-like synoviocytes-RA (HFLS-RA) cells in vitro and their inhibitory mechanism were examined. High inhibitory effects of HLs on the growth of HFLS-RA cells were observed. The induction of apoptosis by HLs was revealed on the basis of flow cytometric analysis. Furthermore, therapeutic effects of HLs in the mouse model with RA were examined in vivo. Our results demonstrate that HLs showed inhibitory effects on the growth of HFLS-RA cells in vitro along with apoptosis and therapeutic effects in mouse models of RA in vivo.

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“…In a DDS study, the therapeutic effects of the anticancer drug, 1,3-bis(2-chloroethyl)-1-nitrosourea, encapsulated into HLs composed of L-ɑ-dimyristoylphosphatidylcholine (DMPC) and polyoxyethylene (20) sorbitan monolaurate (Tween 20) has been shown in an in vivo rat model of meningeal gliomatosis (Kitamura et al., 1996 ). In contrast, HLs composed of DMPC and polyoxyethylenedodecyl ether, without encapsulated anticancer drugs, was shown to inhibit the growth of various type of tumor cells and inducing apoptosis both in vitro (Matsumoto et al., 1999 , 2005 ; Iwamoto et al, 2005 ; Nagami et al., 2006 ; Komizu et al., 2011 ) and in vivo (Shimoda et al., 2009 ; Ichihara et al., 2012 , 2015 ). The therapeutic effects of HLs not containing encapsulated drugs, as an anticancer drug in patients with lymphoma has been reported (Ichihara et al., 2008 ).…”

Section: Introductionmentioning

confidence: 99%

Hybrid liposomes showing enhanced accumulation in tumors as theranostic agents in the orthotopic graft model mouse of colorectal cancer

2018

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Hybrid liposomes (HLs) can be prepared by simply sonicating a mixture of vesicular and micellar molecules in a buffer solution. This study aimed to elucidate the therapeutic effects and ability of HLs to detect (diagnosis) cancer in an orthotopic graft mouse model of colorectal cancer with HCT116 cells for the use of HLs as theranostic agents. In the absence of a chemotherapeutic drug, HLs exhibited therapeutic effects by inhibiting the growth of HCT116 colorectal cancer cells in vitro, possibly through an increase in apoptosis. Intravenously administered HLs also caused a remarkable reduction in the relative cecum weight in an orthotopic graft mouse model of colorectal cancer. A decrease in tumor size in the cecal sections was confirmed by histological analysis using HE staining. TUNEL staining indicated an induction of apoptosis in HCT116 cells in the orthotopic graft mouse model of colorectal cancer. For the detection (diagnosis) of colorectal cancer by HLs, the accumulation of HLs encapsulating a fluorescent probe (ICG) was observed in HCT116 cells in the in vivo colorectal cancer model following intravenous administration. These data indicate that HLs can accumulate in tumor cells in the cecum of the orthotopic graft mouse model of colorectal cancer for a prolonged period of time, and inhibit the growth of HCT116 cells.

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Two methylene groups in phospholipids distinguish between apoptosis and necrosis for tumor cells

Cited by 20 publications

References 13 publications

Phase Behavior of a Lipid Bilayer System Studied by a Replica-Exchange Molecular Dynamics Simulation

Phase Behavior of a Lipid Bilayer System Studied by a Replica-Exchange Molecular Dynamics Simulation

Therapeutic effects of hybrid liposomes without drugs for rheumatoid arthritis

Hybrid liposomes showing enhanced accumulation in tumors as theranostic agents in the orthotopic graft model mouse of colorectal cancer

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