Human Cervix Epitheloid Research Articles

Evaluation of Antiproliferative Palladium(II) Complexes of Synthetic Bisdemethoxycurcumin towards In Vitro Cytotoxicity and Molecular Docking on DNA Sequence.

Metallodrugs form a large family of therapeutic agents against cancer, among which is cisplatin, a paradigmatic member. Therapeutic resistance and undesired side effects to Pt(II) related drugs, prompts research on different metal–ligand combinations with potentially enhanced biological activity. We present the synthesis and biological tests of novel palladium(II) complexes containing bisdemethoxycurcumin (BDMC) 1 and 2. Complexes were fully characterized and their structures were determined by X-ray diffraction. Their biological activity was assessed for several selected human tumor cell lines: Jurkat (human leukaemic T-cell lymphoma), HCT-116 (human colorectal carcinoma), HeLa (human cervix epitheloid carcinoma), MCF-7 (human breast adenocarcinoma), MDA-MB-231 (human mammary gland adenocarcinoma), A549 (human alveolar adenocarcinoma), Caco-2 (human colorectal carcinoma), and for non-cancerous 3T3 cells (murine fibroblasts). The cytotoxicity of 1 is comparable to that of cisplatin, and superior to that of 2 in all cell lines. It is a correlation between IC50 values of 1 and 2 in the eight studied cell types, promising a potential use as anti-proliferative drugs. Moreover, for Jurkat cell line, complexes 1 and 2, show an enhanced activity. DFT and docking calculations on the NF-κB protein, Human Serum Albumin (HSA), and DNA were performed for 1 and 2 to correlate with their biological activities.

In vitro evaluation of immunobiological activity of simple mannolipids

Immunomodulation, cytotoxicity and anti-cancer activity of selected amphiphilic non-ionic (thio)alkyl α-D-mannosides (with aglycone of C6-C12) were investigated in vitro in human cervix epitheloid carcinoma cell line HeLa, murine melanoma cancer cells B16, murine lymphocytic leukemia cell line L1210, murine fibroblast cell line NIH 3 T3 and murine macrophage cell line RAW 264.7. Toxicological studies revealed structure-dependent immunobiological effectivity based on a tight interaction with relevant cells. The results demonstrated diverse immunomodulation of macrophage cell-line RAW264.7 proliferation and production of Th1 and Th2 cytokines, and induction of pro-inflammatory interleukins IL-1α, TNFα, IL-6, IL-12 and IL-17 and anti-inflammatory IL-10 following (thio)alkyl α-D-mannosides 24 and 48 h exposure. Direct application of alkyl mannosides MOC10 and MOC12 and their thio analogues MSC10 and MSC12 in reconstructed human EpiDerm™ and MOC12 and MSC12 in EpiOcular™ model assays for dermal and ocular irritation together with quantification of human proinflammatory cytokines IL-1α, TNFα, IL-6 and IL-8 culture media release was used to ascertain toxicological safety.

Cytoprotective Activity of Neichitti (Vernonia cinerea) in Human Embryonic Kidney (HEK293) Normal Cells and Human Cervix Epitheloid Carcinoma (HeLa) Cells against Cisplatin Induced Toxicity: A Comparative Study

Introduction: Traditional Siddha Medicine literatures suggest to use the decoction of Vernonia cinerea (VC) to alleviate toxic effects caused by metals. Cisplatin, a metal used in cancer treatment is known to cause nephrotoxicity.Aim: To evaluate and compare protective activity of aqueous extract and fractions of VC in Human Embryonic Kidney (HEK293) cells and Human Cervix Epitheloid Carcinoma (HELA) cell lines against cisplatin induced cytotoxicity.Materials and Methods: The Crude Aqueous Extract (CAE) was obtained from whole plant of VC. CAE was fractioned using nonpolar to polar solvents, and Butanol Fraction (BF) as well as Aqueous Fractions (AF) were obtained. The cell lines were exposed with the IC50 dose of cisplatin, then treated with different doses of the extract or fractions. After 48 hours of incubation, viable cell growth was determined by MTT reduction assay in all the treatments by observing at absorbance of 540 nm. Dose response (% cell viability) curve was drawn and the values were statistically compared using One-Way ANOVA, followed by Dunnett’s (2-sided) post-hoc test.Results: Aqueous fraction showed 2.8 times higher cytoprotection (improvement in cell viability by 54%) than CAE against cisplatin induced toxicity in HEK293 cells. BF did not show protective activity in HEK293 cells. In HELA cells, AF showed 1.73 times higher cytoprotection than CAE and 1.55 times higher cytoprotection than BF against cisplatin, as evidenced by improvement in cell viability by 30%, 11% and 13% in AF, CAE and BF respectively. AF exhibited 80% higher cytoprotection against cisplatin cytotoxicity in normal HEK293 than cancer HELA cells. Whereas, CAE and BF showed lesser cytoprotective activity than AF.Conclusion: This study created scientific basis for using Vernonia cinerea against metal toxicities in Siddha system and suggests that the AF is suitable for further discovery of drug that selectively protect normal renal cell during cisplatin treatment in cancer patients.

Cellular oxidative stress and antiproliferative effects of Cordia dichotoma (Linn.) seeds extract and their fractions on human cervix epitheloid (HeLa) and human lung (A549) carcinoma cells

IntroductionCordia dichotoma (Linn.) is an ethnobotanically important plant species traditionally used for the treatment of several diseases in humans. The present study was aimed to explore the oxidative and anticancer properties of Cordia dichotoma seeds extract (MECD) along with its fractions against Human Cervix Epitheloid (HeLa) and human lung (A549) carcinoma cell lines. MethodsCrude extract of Cordia dichotoma seeds was prepared in methanol by continuous hot soxlation technique and the extract was concentrated to dryness. For the purpose of standardization of crude extract, HPTLC profiling of extract was done and finally, three different fractions namely chloroform, ethyl acetate, and the aqueous fraction was prepared using column chromatography. The cellular oxidative stress potential was measured in the term of intracellular reactive oxygen species (ROS) levels whereas anti-proliferative potential was evaluated by cell viability (MTT) assay, nuclear staining assays such as PI-Exclusion and Hoestch/PI double staining for the analysis of induction of apoptosis. Cellular morphology was also performed using inverted phase contrast microscope and percentage apoptosis along with apoptotic cell ratio was calculated. ResultsExposure to crude extract and their fractions in the dose ranging from 25 μg/mL to 250 μg/mL, significantly inhibited the cell viability (p < 0.001) in a dose-dependent manner. Fluorescence microscopy analysis and intracellular ROS generation exhibited significant ROS induction that might trigger the apoptotic pathways leading to the death of cancerous cells. ConclusionOur results suggest that the methanolic extract of Cordia dichotoma seeds as well as its aqueous fraction possesses maximum cytotoxicity against human cervix epitheloid (HeLa) and human lung (A549) cancer cell lines.

Antioxidant and cytotoxic activity of the acetone extracts of root of Euphorbia hylonoma and its ellagic acid derivatives

The acetone extracts and fractions prepared from the roots of Euphorbia hylonoma were investigated for 1, 1-diphenyl-2-pycrylhydrazyl (DPPH) free radical, superoxide anion and hydroxyl radical scavenging activity and cytotoxic activity against the human hepatoma cell line SMMC-7721, human cervix epitheloid carcinoma cell line HeLa and the human gastric cancer cell line SGC-7901. The acetone extract and fraction of EtOAc showed high antioxidant activities. The acetone extract and fraction of water showed a stronger cytotoxic effect on all tested cells, with IC50 values being less than 20 μg/mL. The acetone extract and fraction of water induced cell cycle arrest in G1 phase in SMMC-7721 cells. The major compounds isolated from the acetone extract were ellagic acid derivatives and showed weak cytotoxic activities on the tested cell lines, and these compound were 3,3i‚¢,4-tri-O-methylellagic acid (1), 3,3i‚¢-di-O-methylellagic acid (2), 3-O-methylellagic acid (3) and 3,3i‚¢-di-O-methylellagic acid-4i‚¢-O-β-dxylopyranosid (4). Compound 3 showed better obvious radical scavenging activity than other tested compounds. Key words: Euphorbia hylonorma Hand-Mazz, antioxidant activity, cytotoxic activity, chemical constituents.

Antioxidant and cytotoxic activity of the acetone extracts of root of Euphorbia hylonoma and its ellagic acid derivatives

The acetone extracts and fractions prepared from the roots of Euphorbia hylonoma were investigated for 1, 1-diphenyl-2-pycrylhydrazyl (DPPH) free radical, superoxide anion and hydroxyl radical scavenging activity and cytotoxic activity against the human hepatoma cell line SMMC-7721, human cervix epitheloid carcinoma cell line HeLa and the human gastric cancer cell line SGC-7901. The acetone extract and fraction of EtOAc showed high antioxidant activities. The acetone extract and fraction of water showed a stronger cytotoxic effect on all tested cells, with IC50 values being less than 20 μg/mL. The acetone extract and fraction of water induced cell cycle arrest in G1 phase in SMMC-7721 cells. The major compounds isolated from the acetone extract were ellagic acid derivatives and showed weak cytotoxic activities on the tested cell lines, and these compound were 3,3’,4-tri-O-methylellagic acid (1), 3,3’-di-O-methylellagic acid (2), 3-O-methylellagic acid (3) and 3,3’-di-O-methylellagic acid-4’-O-β-dxylopyranosid (4). Compound 3 showed better obvious radical scavenging activity than other tested compounds. Key words: Euphorbia hylonorma Hand-Mazz, antioxidant activity, cytotoxic activity, chemical constituents.

Glycosaminoglycans and syndecan-4 are involved in SDF-1/CXCL12-mediated invasion of human epitheloid carcinoma HeLa cells

Background In addition to their physiologic effects in inflammation and angiogenesis, chemokines are involved in cancer pathology. The CXC-chemokine stromal cell-derived factor-1 (SDF-1)/CXCL12 mediates its biological activities through activation of G protein-coupled receptor CXCR4 and binds to glycosaminoglycans (GAGs). Methods Using Bio-coat cell migration chambers, specific antagonists, flow cytometry and RNA interference, we evaluate the involvement of heparan sulfate proteoglycans (HSPG) in the SDF-1/CXCL12-induced invasion of human cervix epitheloid carcinoma HeLa cells. Results The SDF-1/CXCL12-induced cell invasion is dependent on CXCR4. Furthermore, Protein Kinase C delta (PKC δ) and c-jun NH2-terminal kinase/stress-activated protein kinase (JNK/SAPK) are implicated in this event, but not extracellular signal-regulated kinase (ERK) 1/2. Moreover, the invasion of HeLa cells induced by SDF-1/CXCL12 was dependent on matrix metalloproteinase-9 (MMP-9). The pre-incubation of HeLa cells with heparin or with anti-heparan sulfate antibodies or with β- d-xyloside inhibited SDF-1/CXCL12-mediated cell invasion. Furthermore, the down-regulation of syndecan-4, a heparan sulfate proteoglycan, decreased SDF-1/CXCL12-mediated HeLa cell invasion. GAGs, probably on syndecan-4, are involved in SDF-1/CXCL12-mediated cell chemotaxis. General significance These data suggest that targeting the glycosaminoglycan/chemokine interaction could be a new therapeutic approach for carcinomas in which SDF-1/CXCL12 is involved.

Quercetin‐induced apoptotic cascade in cancer cells: Antioxidant versus estrogen receptor α‐dependent mechanisms

The flavonol quercetin, especially abundant in apple, wine, and onions, is reported to have anti-proliferative effects in many cancer cell lines. Antioxidant or pro-oxidant activities and kinase inhibition have been proposed as molecular mechanisms for these effects. In addition, an estrogenic activity has been observed but, at the present, it is poorly understood whether this latter activity plays a role in the quercetin-induced anti-proliferative effects. Here, we studied the molecular mechanisms of quercetin committed to the generation of an apoptotic cascade in cancer cells devoid or containing transfected estrogen receptor alpha (ERalpha; i.e., human cervix epitheloid carcinoma HeLa cells). Although none of tested quercetin concentrations increase reactive oxygen species (ROS) generation in HeLa cells, quercetin stimulation prevents the H(2)O(2)-induced ROS production both in the presence and in the absence of ERalpha. However, this flavonoid induces the activation of p38/MAPK, leading to the pro-apoptotic caspase-3 activation and to the poly(ADP-ribose) polymerase cleavage only in the presence of ERalpha. Notably, no down-regulation of survival kinases (i.e., AKT and ERK) was reported. Taken together, these findings suggest that quercetin results in HeLa cell death through an ERalpha-dependent mechanism involving caspase- and p38 kinase activation. These findings indicate new potential chemopreventive actions of flavonoids on cancer growth.

Synthesis and in vitro anti-proliferative activity of β-elemene monosubstituted derivatives in HeLa cells mediated through arrest of cell cycle at the G1 phase

β-Elemene monosubstituted amine, ether and rhenium coordinated complex were synthesized. Their structures were characterized by IR, 1H NMR, 13C NMR, HRMS or EA. Their IC 50 on HeLa cell lines, cell cycle and protein expression of G 1 phase (Cyclin D 1, Rb, P-Rb) were detected respectively by the method of WST-1, Flow Cytometry and Western Blot. The Results showed that the in vitro anti-proliferative activity of β-elemene monosubstituted amine and Re(CO) 3-β-elemene derivatives in human cervix epitheloid carcinoma HeLa cells were improved significantly compared with both of ether derivatives and parent β-elemene. These derivatives could reduce Rb phosphorylation and cyclin D 1 protein expression to arrest the cell cycle at G 1 phase.

Zigzag-shaped supramolecular networks formed via hydrogen bonding. Crystal structures, DNA binding, and cytotoxic activity of a new palladium(II) complex

A single-ligand complex Pd(II)-L-aspartic acid was synthesized and characterized by elemental ana-lysis and IR spectra. The crystal structure of the complex was determined by single crystal X-ray diffraction (crystallizing in orthorhombic crystal system, space group P212121 with unit cell parameters a = 5.3145(11) A, b = 9.6294(19) A, c = 22.233(4) A, and Z = 4). The Pd atom was four-coordinated with N(1), N(2), O(4), and O(5) from two L-aspartic ligands and formed a slightly distorted parallelogram geometry. 2D “zigzag” shaped supramolecular networks are constructed via hydrogen bonding. The binding of the title complex with fish sperm DNA (FS-DNA) has been investigated by absorption and fluorescence spectra and the results indicate that the complex bind to FS-DNA in an intercalative mode. Gel electrophoresis shows the cleavage of both supercoiled and circular pBR322 DNA to form a small molecular fragment under the action of the title complex. The cytotoxicity assay proves that the complex has strong anticancer activity to human cervix epitheloid carcinoma cell lines (HeLa).

인체 말초혈액의 활성화 과정 중 yippee-like 5 (YPEL5) 유전자의 발현 양상

Yippee 패밀리를 구성하는 yippee-유사 단백질들은 한 개의 zinc-finger 도메인을 지닌 Drosophila yippee 단백질의 homolog로서 모든 진핵생물에 존재하는 것으로 알려졌으나 그 기능은 밝혀진 바가 없다. 인체 T 림프구의 활성화과정 중 발현수준이 변화하는 유전자들을 선별하기 위해 인체 말초혈액에서 분리한 resting T 세포, immobilized anti-CD3에 의해 26시간 혹은 30시간 동안 활성화시킨 T 세포로부터 각각 정제한 total RNA를 이용하여 ODD-PCR을 수행한 결과, resting T 세포에서는 발현되지만 immobilized anti-CD3 활성화에 의해 세포주기를 개시하여 <TEX>$G_1/S$</TEX> boundary에 도달한 T 세포들로부터는 전혀 발현되지 않는 흥미로운 유전자로서 Drosophila yippee 단백질 유전자의 인체 homolog인 YPEL5 유전자를 분리하였다. 노던 블로팅법으로 T 세포 활성화에 뒤이은 YPEL5 mRNA의 발현 변화를 조사한 결과, <TEX>${\sim}2.2kb$</TEX> 크기의 YPEL5 mRNA는 resting T 세포를 비롯하여 immobilize anti-CD3에 의한 활성화 후 1.5시간까지는 확인되었으나 활성화 후 5시간 이후부터 48시간에 이르는 시간에는 전혀 확인되지 않았다. YPEL5 단백질을 GFP-fusion 단백질로서 인체 암세포주인 HeLa 세포에 transfection하여 발현시킨 결과, GFP-YPEL5 단백질이 모두 핵에 위치하는 것으로 나타나 YPEL5 단백질이 핵단백질임을 확인하였다. 또한 YPEL5의 기능을 규명하기 위해 YPEL5 발현벡터를 HeLa 세포에 transfection 하고 발현시켜 HeLa 세포의 증식에 미치는 YPEL5의 영향을 MTT assay로 분석한 결과, vector plasmid를 transfection시킨 대조구의 47% 수준으로 세포증식이 감소하는 것으로 나타났다. 이러한 결과들은 YPEL5 mRNA의 발현이 T 세포 수용체를 통한 T 세포 활성화의 초기단계에 현저히 감소됨을 보여주며, 또한 YPEL5가 핵단백질로서 세포증식에 대해 저해효과를 미칠 수 있음을 시사한다. Yippee-like proteins, which have been identified as the homolog of Drosophila yippee protein containing a zinc-finger domain, are known to be highly conserved among eukaryotes. However, their functional roles are still poorly understood. Recently we initiated ordered differential display (ODD)-polymerase chain reaction (PCR) to isolate genes of which expressions are altered following activation of human T cells. On the ODD-PCR image, one PCR-product detected in unstimulated T cells was not detectable at the time when the activated T cells traversed near <TEX>$G_1/S$</TEX> boundary following activation by immobilized anti-CD3. Cloning and nucleotide sequence analysis revealed that the PCR-product was yippee-like 5 (YPEL5) gene, which was known as a human homolog of the Drosophila yippee gene. Northern blot analysis confirmed the amount of <TEX>${\sim}2.2$</TEX> kb YPEL5 mRNA expression detectable in unstimulated T cells was sustained until 1.5 hr after activation and then rapidly declined to undetectable level by 5 hr. Ectopic expression of YPEL5 gene in human cervix epitheloid carcinoma HeLa cells caused a significant reduction in cell proliferation to the level of 47% of the control. Expression of GFP-YPEL5 fusion protein in HeLa cells showed its nuclear localization. These results demonstrated that the expression level of human YPEL5 mRNA was negatively regulated in the early stage of T cell activation, and suggested that YPEL5 might exert an inhibitory effect on the cell proliferation as a nuclear protein.

Evaluation of cytotoxic activities of some medicinal polypore fungi from China

The petrol ether, ethyl acetate and methanol extracts of eight medicinal polypore fungi from China were evaluated for cytotoxic activities using MTT-dye assay. All the petrol ether and ethyl acetate extracts exhibited cytotoxicity against human cervix epitheloid carcinoma cell lines (Hela) and human hepatoma cell lines (SMMC-7721). Cytotoxicity activity was also observed in the methanol extracts of Phellinus conchatus and Pycnoporus sanquineus, but the methanol extracts from Cryptoporus volvatus, Fomitopsis pinicola, Fomes hornodermus, Lenzites betulina, Trametes gibbosa and Trametes orientalis showed weak activity when compared with quercetin.

The synthesis and anti-proliferative effects of β-elemene derivatives with mTOR inhibition activity

Fourteen β-elemene derivatives containing a piperazine, a morpholine, a tetrahydropyrrole, a thiophenylethylamine, or a cyclohexamine group were synthesized. The structures of these β-elemene derivatives were characterized with IR, 1H NMR, MS, and elemental analyses. All these derivatives had an increased anti-proliferative activity in human cervix epitheloid carcinoma HeLa, gastric carcinoma SGC-7901, and leukemia K562 cells comparing with that of β-elemene. Among these derivatives, 13,14-bis( cis-3,5-dimethyl-1-piperazinyl)-β-elemene ( IIi), 13,14-bis[2-(2-thiophenyl)ethylamino]-β-elemene ( IIm), and 13,14-bis(cyclohexamino)-β-elemene ( IIn) were the most potent agents. IIi, IIm, and IIn inhibited K562 cell growth with an IG 50 below 5 μM that was correlated with mTOR activity inhibition.

Mechanisms of Naringenin‐induced Apoptotic Cascade in Cancer Cells: Involvement of Estrogen Receptor a and ß Signalling

The flavanone naringenin (Nar), especially abundant in the Mediterranean diet, is reported to have anti-proliferative effects in many cancer cell lines. Antioxidant activities, kinase and glucose uptake inhibition have been proposed as molecular mechanisms for these effects. In addition, an anti-estrogenic activity has been observed but, at the present, it is poorly understood whether this latter activity could play a role in the Nar anti-tumoral effects. Here, we tested the ability of Nar to activate a specific, rapid signal transduction pathway committed to the generation of an apoptotic cascade in the presence of one of the two estrogen receptor (ER) isoforms (i.e., ERalpha or ERbeta). Cancer cells containing transfected (human cervix epitheloid carcinoma HeLa cells) or endogenous ERalpha (human hepatoma HepG2 cells) or ERbeta (human colon adenocarcinoma DLD-1 cells) were used. Our results show that Nar exerts an anti-proliferative effect only in the presence of ERalpha or ERbeta. Moreover, Nar stimulation induces the activation of p38/MAPK leading to the pro-apoptotic caspase-3 activation and to the poly(ADP-ribose) polymerase cleavage in all cancer cell lines considered. Notably, Nar shows an anti-estrogenic effect only in ERalpha containing cells; whereas in ERbeta containing cells, Nar mimics the 17beta-estradiol effects. These findings indicate new steps in the mechanism underlying ER-dependent anti-proliferative effects of Nar suggesting new potential chemopreventive actions of flavonoids on cancer growth.

Nutritional flavonoids modulate estrogen receptor alpha signaling.

Estrogen receptor alpha (ERalpha) mediates 17beta-estradiol (E2) actions through the transcription of E2-sensitive target genes. In addition, rapid non-genomic signaling (e.g., MAPK/ERK) occurs. It is now well accepted that these rapid membrane-initiated responses account for E2-related cancer. Beside many beneficial effects on human health, nutritional flavonoids exert protective and anticarcinogenic effects on E2-related cancer. The mechanism underlying these effects seems to be related to flavonoids antioxidant properties and/or to their ability to alter signal transduction protein kinases. In addition, an antiestrogenic activity has been proposed but not yet defined. However, the identification and characterization of the responsible mechanisms for flavonoid antitumoral effects is poorly understood. Here, we investigated the possibility that the antimitogenic effects of flavonoids are transduced by modulating ERalpha-mediated rapid signaling. The ability of two flavonoids, the flavanone naringenin and the flavanol quercetin, with respect of E2, to induce ERalpha activities has been studied in the human cervix epitheloid carcinoma cell line (HeLa) devoid of any estrogen receptors and rendered E2-sensitive by transient transfection with a human ERalpha expression vector. Our results indicate that flavonoids act as E2 mimetic on ERalpha transcriptional activity, whereas they impair the activation of rapid signaling pathways committed to E2-induced proliferation. The resulting decoupling of ERalpha signal transduction could be proposed as a new mechanism in the protective effects of flavonoids against E2-related cancer.

Gold(III) porphyrins as a new class of anticancer drugs: cytotoxicity, DNA binding and induction of apoptosis in human cervix epitheloid cancer cells.

A series of gold(III) tetraarylporphyrins are stable in the presence of glutathione and exert much higher potency than cisplatin in killing human cancer cells, including the drug-resistant variants; the gold-induced cytotoxicity occurs through an apoptotic pathway according to laser confocal microscopy and flow cytometric studies.

THE ANTIPROLIFERATIVE RIMINOPHENAZINE AGENTS CLOFAZIMINE AND B669 PROMOTE LYSOPHOSPHOLIPID-MEDIATED INHIBITION OF NA+, K+-ADENOSINE TRIPHOSPHATASE-ACTIVITY IN CANCER CELL-LINES IN-VITRO

The effects of the anti-proliferative, phospholipase A(2) (PLA(2))-activating riminophenazine agents, clofazimine and B669, on the Na+, K+-adenosine triphosphatase activity of the FaDu human pharynx squamous carcinoma cell line have been investigated in vitro. At concentrations of 1.25-10 mu g/ml both agents caused dose-related enhancement of PLA(2), as measured by increased release of lysophosphatidylcholine (LPC), and inhibition of Na+, K+-ATPase in intact cells and isolated membrane preparations. The inhibitory effects of both riminophenazines on the Na+, K+-ATPase activity of FaDu cells were mimicked by reagent LPC and prevented by treatment of the cells with the lysophospholipid-neutralizing agents alpha-tocopherol and lysophospholipase. Riminophenazine-mediated inhibition of Na+, K+-ATPase activity was also observed with the HeLa (human cervix epitheloid carcinoma) and T24 (human transitional cell bladder carcinoma) cell lines. The anti-proliferative activity of clofazimine and B669 is therefore probably achieved by lysophospholipid-mediated inactivation of Na+, K+-ATPase.