Lipid Efflux Mediated by Alkylphospholipids in HepG2 Cells

Ríos-Marco, Pablo; Segovia, J.L.; Jiménez-López, José M.; Marco, Carmen; Carrasco, Marı́a P.

doi:10.1007/s12013-013-9518-7

Cited by 2 publications

(1 citation statement)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Conversely, etoposide used for the treatments of lung, testicular and ovarian cancer, lymphoma, leukemia, and neuroblastoma, and cytarabine used to treat acute myeloid leukemia, acute lymphocytic leukemia, chronic myelogenous leukemia, and non-Hodgkin’s lymphoma promote nSMase activation, leading to reduced surface membrane SM content and Cer accumulation [ 46 , 47 , 69 ]. The phospholipid analogue miltefosine, which has been approved for the treatment of breast cancer metastasis, and is currently used for the treatment of cutaneous metastases of mammary carcinoma was shown to significantly inhibit SM biosynthesis in human hepatoma and other tumor cells [ 87 ], promote efflux of cholesterol and SM from the surface membrane [ 88 ], and modulate membrane physical properties [ 89 ]. The anti-cancer drug daunorubicin induced specific activation of nSMase-2 in the human breast cancer cell line MCF-7, leading to depletion of surface membrane SM and accumulation of intracellular Cer [ 90 ].…”

Section: Tumor Immune Evasionmentioning

confidence: 99%

Cell surface sphingomyelin: key role in cancer initiation, progression, and immune evasion

2021

View full text Add to dashboard Cite

Cell surface biochemical changes, notably excessive increase in outer leaflet sphingomyelin (SM) content, are important in cancer initiation, growth, and immune evasion. Innumerable reports describe methods to initiate, promote, or enhance immunotherapy of clinically detected cancer, notwithstanding the challenges, if not impossibility, of identification of tumor-specific, or associated antigens, the lack of tumor cell surface membrane expression of major histocompatibility complex (MHC) class I alpha and β2 microglobulin chains, and lack of expression or accessibility of Fas and other natural killer cell immune checkpoint molecules. Conversely, SM synthesis and hydrolysis are increasingly implicated in initiation of carcinogenesis and promotion of metastasis. Surface membrane SM readily forms inter- and intra- molecular hydrogen bond network, which excessive tightness would impair cell-cell contact inhibition, inter- and intra-cellular signals, metabolic pathways, and susceptibility to host immune cells and mediators. The present review aims at clarifying the tumor immune escape mechanisms, which face common immunotherapeutic approaches, and attracting attention to an entirely different, neglected, key aspect of tumorigenesis associated with biochemical changes in the cell surface that lead to failure of contact inhibition, an instrumental tumorigenesis mechanism. Additionally, the review aims to provide evidence for surface membrane SM levels and roles in cells resistance to death, failure to respond to growth suppressor signals, and immune escape, and to suggest possible novel approaches to cancer control and cure.

show abstract

Section: Tumor Immune Evasionmentioning

confidence: 99%

Cell surface sphingomyelin: key role in cancer initiation, progression, and immune evasion

2021

View full text Add to dashboard Cite

show abstract

Alkylphospholipids: An update on molecular mechanisms and clinical relevance

Ríos-Marco

Marco

Gálvez

et al. 2017

Biochimica et Biophysica Acta (BBA) - Biomembranes

View full text Add to dashboard Cite

Alkylphospholipids (APLs) represent a new class of drugs which do not interact directly with DNA but act on the cell membrane where they accumulate and interfere with lipid metabolism and signalling pathways. This review summarizes the mode of action at the molecular level of these compounds. In this sense, a diversity of mechanisms has been suggested to explain the actions of clinically-relevant APLs, in particular, in cancer treatment. One consistently reported finding is that APLs reduce the biosynthesis of phosphatidylcholine (PC) by inhibiting the rate-limiting enzyme CTP:phosphocholine cytidylyltransferase (CT). APLs also alter intracellular cholesterol traffic and metabolism in human tumour-cell lines, leading to an accumulation of cholesterol inside the cell. An increase in cholesterol biosynthesis associated with a decrease in the synthesis of choline-containing phospholipids and cholesterol esterification leads to a change in the free-cholesterol:PC ratio in cells exposed to APLs. Akt phosphorylation status after APL exposure shows that this critical regulator for cell survival is modulated by changes in cholesterol levels induced in the plasma membrane by these lipid analogues. Furthermore, APLs produce cell ultrastructural alterations with an abundant autophagic vesicles and autolysosomes in treated cells, indicating an interference of autophagy process after APL exposure. Thus, antitumoural APLs interfere with the proliferation of tumour cells via a complex mechanism involving phospholipid and cholesterol metabolism, interfere with lipid-dependent survival-signalling pathways and autophagy. Although APLs also exert antiparasitic, antibacterial, and antifungal effects, in this review we provide a summary of the antileishmanial activity of these lipid analogues. This article is part of a Special Issue entitled: Membrane Lipid Therapy: Drugs Targeting Biomembranes edited by Pablo V. Escribá.

show abstract

Lipid Efflux Mediated by Alkylphospholipids in HepG2 Cells

Cited by 2 publications

References 36 publications

Cell surface sphingomyelin: key role in cancer initiation, progression, and immune evasion

Cell surface sphingomyelin: key role in cancer initiation, progression, and immune evasion

Alkylphospholipids: An update on molecular mechanisms and clinical relevance

Contact Info

Product

Resources

About