DigitalUM :: Browsing by Subject "Cell death"

Browsing by Subject "Cell death"

Now showing 1 - 20 of 20

Open Access
A compressive review about Taxol® : history and future challenges
(MDPI, 2020-12-17) Gallego Jara, Julia; Lozano Terol, Gema; Sola Martinez, Rosa Alba; Cánovas Diaz, Manuel; De Diego Puente, María Teresa; Bioquímica y Biología Molecular B e Inmunología
Taxol®, which is also known as paclitaxel, is a chemotherapeutic agent widely used to treat different cancers. Since the discovery of its antitumoral activity, Taxol® has been used to treat over one million patients, making it one of the most widely employed antitumoral drugs. Taxol® was the first microtubule targeting agent described in the literature, with its main mechanism of action consisting of the disruption of microtubule dynamics, thus inducing mitotic arrest and cell death. However, secondary mechanisms for achieving apoptosis have also been demonstrated. Despite its wide use, Taxol® has certain disadvantages. The main challenges facing Taxol® are the need to find an environmentally sustainable production method based on the use of microorganisms, increase its bioavailability without exerting adverse effects on the health of patients and minimize the resistance presented by a high percentage of cells treated with paclitaxel. This review details, in a succinct manner, the main aspects of this important drug, from its discovery to the present day. We highlight the main challenges that must be faced in the coming years, in order to increase the effectiveness of Taxol® as an anticancer agent.
Open Access
Cellular death linked to irreversible stress in the sarcoplasmic reticulum: the effect of inhibiting Ca(2+) -ATPase or protein glycosylation in the myocardiac cell model H9c2
(2007-10) Lax Pérez, Antonio Manuel; Soler, Fernado; Fernandez Belda, Francisco; Medicina
Experimental sarcoplasmic reticulum damage induced by 3 microM thapsigargin or 1 microg/ml tunicamycin provoked viability loss of the cell population in approximately 72 h. Release of cytochrome c from mitochondria was an early event and Bax translocation to the mitochondria preceded or was simultaneous with cytochrome c release. The release of cytochrome c was not related with mitochondria depolarization or caspase activation. Irreversible stress in the sarcoplasmic reticulum, detected by the early activation of caspase 12, was functionally linked to the mitochondrial apoptotic pathway. Caspase 3 processing was blocked by cells preincubation with a selective inhibitor of either caspase 9 or caspase 8 whereas caspase 8 activation was inhibited by a selective caspase 9 inhibitor. This was consistent with the involvement of caspase 8 in a positive feedback loop leading to amplify the caspase cascade. Caspase inhibition did not protect against cell death indicating the existence of alternative caspase-independent mechanisms.
Embargo
Cytotoxicity and alterations at transcriptional level caused by metals on fish erythrocytes in vitro
(Springer, 2016-03-15) Morcillo, Patricia; Romero, Diego; Meseguer, José; Esteban Abad, María Ángeles; Cuesta, Alberto; Ciencias Sociosanitarias
The in vitro use of fish erythrocytes to test the toxicity of aquatic pollutants could be a valuable alternative to fish bioassays but has received little attention. In this study, erythrocytes from marine gilthead sea bream (Sparus aurata L.) and European sea bass (Dicentrarchus labrax L.) specimens were exposed for 24 h to Cd, Hg, Pb and As and the resulting cytotoxicity was evaluated. Exposure to metals produced a dose-dependent reduction in the viability, and mercury showed the highest toxicity followed by MeHg, Cd, As and Pb. Moreover, fish erythrocytes incubated with each one of the metals exhibited alteration in gene expression profile of metallothionein, superoxide dismutase, catalase, peroxiredoxin, glutathione reductase, heat shock proteins 70 and 90, Bcl2-associated X protein and calpain1 indicating cellular protection, stress and apoptosis death as well as oxidative stress. This study points to the benefits for evaluating the toxicological mechanisms of marine pollution using fish erythrocytes in vitro.
Embargo
Effect of mobile phones on micronucleus frequency in human exfoliated oral mucosal cells
(Wiley, 2012-11) Ros Llor, I.; Sánchez Siles, M.; Camacho Alonso, Fabio; López Jornet, María Pía; Dermatología, Estomatología, Radiología y Medicina Física
Objective: In the last two decades, the use of mobile phones has increased enormously all over the world. The controversy regarding whether radiofrequency (RF) fields exert effects upon biological systems is a concern for the general population. An evaluation is made of DNA damage and cytokinetic defects, proliferative potential, and cell death because of RF radiation emitted by mobile phones in healthy young users. Study design: This cohort study was carried out in 50 Caucasian mobile phone users. We collected two cell samples from each subject (a total of 100 cell samples), corresponding to the right and left cheek mucosa, respectively. Case histories and personal information were assessed, including age, gender, body height and weight, history of cancer, smoking and alcohol consumption, exposure to chemical carcinogens or radiation, and dietary habits. Sampling comprised cell collection from both cheeks with a cytobrush, centrifugation, slide preparation, fixation, and staining, followed by fluorescent microscopic analysis. A total of 2000 exfoliated cells were screened for nuclear abnormalities, especially micronucleus. Results: No statistically significant changes were recorded in relation to age, gender, body mass index, or smoking status. A comparison of the results vs the control area according to the side of the face on which the mobile phone was placed, and in relation to the duration of exposure (years) to mobile phone radiation in the total 100 samples, yielded no significant differences. Conclusions: No genotoxic effects because of RF exposure were observed in relation to any of the study parameters.
Embargo
Effects of chlorpyrifos on cell death and cellular phenotypic specification of human neural stem cells
(2019-05-18) Motas, M; Sandoval, L; Rosca, A; Oniga, A; Zambrano, A; Ramos, JJ; González, MC; Liste, I; Ciencias Sociosanitarias
Chlorpyrifos (CPF) is an organophosphate pesticide widely used in agriculture, whose traditional and wellknown mechanism of action is the inhibition of the enzyme Acetylcholinesterase (AChE). Subacute exposures to CPF have been associated with alterations different from the inhibition of AChE. Because of the vulnerability of the developing nervous system, prenatal and early postnatal exposures are of special concern. Human neural stem cells (hNSC) provide the opportunity to study early stages of neural development and may be a valuable tool for developmental neurotoxicology (DNT). In the current work, the cell line hNS1 was used as a model system with the aim of validating this cell line as a reliable testing method. To evaluate the effects of CPF on early developmental stages, hNS1 cells were exposed to different concentrations of the pesticide and cell death, proliferation and cell fate specification were analyzed under differentiation conditions. Since hNS1 cells responded to CPF in a similar way to other human cell lines, we consider it may be a valid model for DNT chemical assessment. CPF induced apoptotic cell death only at the highest doses tested, suggesting that it is not toxic for the specific developmental stage here addressed under short term exposure. In addition, the higher doses of CPF promoted the generation of astroglial cells, without affecting neurogenesis.
Open Access
Evaluation of morphology, apoptosis, and cell proliferation of the uterus in postmenopausal women
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2025) Ratajczak, Weronika; Łazowska, Malwina; Laszczyńska, Maria; Rył, Aleksandra; Lubkowska, Anna; Zimny, Małgorzta; Kram, Andrzej; Sipak, Olimpia
Background. The aim of this study was to evaluate the morphology (atrophy and fibrosis), apopto-sis, and cell proliferation in the uterine wall. The research material came from postmenopausal women who had undergone hysterectomy due to uterine myomas or prolapse of the reproductive organ and were not taking menopausal hormone therapy (MTH). Material and Methods. The collected material was divided into three groups. Group I (n=18) con-sisted of uterine sections taken 1 to 5 years after the last menstruation, Group II (n=17) 6 to 10 years after the last menstruation, and Group III (n=15) over 11 years after the last menstruation. To assess morphology and fibrosis, the uterine sections were subjected to hematoxylin and eosin (HE) staining and to Mallory's staining. In addition, we performed a histochemical examination to identify apopto-sis in endometrial and myometrial cells using the TUNEL method. An immunohistochemical analysis of endometrial and myometrial cells was also performed to detect the location of the proliferating cell nuclear antigen (PCNA). Results. Differences in apoptosis were only found in the myometrium between Group I and Group III, and were strongest in Group I myometrial cells, and weakest in Group III. Neither the endome-trium nor the myometrium showed statistically significant differences in the overall percentage of PCNA(+) cells between groups. Conclusion. Morphological changes in the endometrial and myometrial layers of postmenopausal uteri increased with time since the last menstruation.
Open Access
Ferroptosis-relevant mechanisms and biomarkers for therapeutic interventions in traumatic brain injury
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2020) Rui, Tongyu; Li, Qianqian; Song, Shunchen; Gao, Yaxuan; Luo, Chengliang
Traumatic brain injury (TBI) is one of the most significant health care problems worldwide, causing disability and death especially among young individuals. Although a large range of agents and therapies have been proved beneficial to lesions post- TBI to some extent, effective treatments have not been translated to the clinic. As a newly discovered form of iron-dependent regulated cell death, ferroptosis has been implicated in TBI. In this review, we update the current state of knowledge related to second injuries post-TBI, including ferroptosis, oxidative stress, mitochondrial dysfunction, neuroinflammation and so on, which often lead to chronic symptoms and long-term disability. This review systematically summarizes the latest progress in the pathophysiological mechanisms of TBI, with a focus on providing references for proposing new multi- molecular targets for comprehensive therapeutic strategies based on ferroptosis-relevant mechanisms. In addition, biomarkers are essential diagnostic and prognostic tools in TBI. Several biomarkers associated with the outcome of TBI have been listed in this article, such as Pde10a, MDA, UCH-L1, S100A9, S100B, ALDOC, ACSL4, MBP and F2-Isoprostane. Therefore, the understating of ferroptosis-relevant mechanisms and biomarkers may contribute to development of promising therapies for TBI clinical trials.
Open Access
Gasdermin D mediates a fast transient release of ATP after NLRP3 inflammasome activation before ninjurin 1-induced lytic cell death
(Cell Press, 2025) Schachter, Julieta; Guijarro, Adriana; Angosto-Bazarra, Diego; Pinilla, Miriam; Hurtado-Navarro, Laura; Meunier, Etienne; Perez-Oliva, Ana Belen; Schwarzbaum, Pablo J; Pelegrin, P; Bioquímica y Biología Molecular B e Inmunología
Pyroptosis is a lytic cell death triggered by the cleavage of gasdermin (GSDM) proteins and subsequent pore formation by the N-terminal domain oligomerization in the plasma membrane. GSDMD is cleaved by caspase-1/-4/-5/-11 upon inflammasome activation and mediates interleukin (IL)-1β and IL-18 release. GSDMD pores favor ninjurin 1 (NINJ1)-induced plasma membrane rupture and cell death. Here, we demonstrate that GSDMD mediates early ATP release upon NLRP3 inflammasome activation independently of NINJ1, occurring before IL-1β release and cell death and constituting an early danger signal. The release of ATP is a transient signal terminated before the cells continue to permeabilize and die. The different N termini of GSDMA to -E are also able to release ATP and induce monocyte migration toward pyroptotic cells. This study reveals ATP release as an early and transient danger signal depending on GSDMD plasma membrane permeabilization, independently of the late stages of lytic cell death.
Open Access
Histochemical and chronological analysis of mouse submandibular gland parenchyma subjected to abrupt reperfusion
(Murcia : F. Hernández, 2003) Fujisawa, Y.; Aiyama, S.
We examined the effects of abrupt reperfusion on the mouse submandibular gland parenchyma and determined the degree of recovery from tissue damage. A main trophic artery supplying the gland was ligated with silk thread, and the ligature was then released after a variable period. The gland was removed at various times after reperfusion and then examined immunohistochemically and ultrastructurally. With reperfusion after 15 or 30 min of ligation, the tissue damage to the glands was slight or inapparent. With reperfusion after 1 or 3 h of ligation, collapse of the acini and the ducts was observed in parts of the lobules, but restoration of the parenchymal structures occurred, with the appearance of PCNA-positive cells, although there were differences in the level of restoration. After 6 h of ligation, most of the normal parenchymal cells had disappeared by the 5th and 7th days after reperfusion, and apoptosis and necrosis were present. These findings suggest that if interruption of the blood supply to the submandibular gland parenchyma is limited to within a few hours, then tissue repair after reperfusion is possible, although this will differ according to the level of damage, because the acini and the ducts reappear, probably with proliferation of parenchymal cells.
Embargo
In vitro evaluation of cell death induced by cadmium, lead and their binary mixtures on erythrocytes of Common buzzard (Buteo buteo)
(Elsevier, 2013-11-25) Hernández-García, A.; Romero, D.; Gómez-Ramírez, P.; María-Mojica, P.; Martínez-López, E.; García-Fernández, A. J.; Ciencias Sociosanitarias
Cadmium and lead are persistent and ubiquitous metals that can cause several deleterious effects in living beings. Apoptosis and necrosis are two types of cell death that can be found after in vivo and in vitro exposure to these metals. In this study, isolated red blood cells from living captive Common buzzard (Buteo buteo) were exposed in vitro to different concentrations of lead, cadmium, and the mixture lead–cadmium in a proportion of 1:10 (similar to that found in previous field studies). Data obtained from dose–response curves were used to evaluate the interactive effects of metal mixtures on cell viability. In general, except for the exposure to NOEC, additivity was the most frequently observed response. As described in human, after in vitro exposure, lead was highly accumulated in buzzard erythrocytes, while cadmium accumulation was scarce. Finally, the type of cell death (apoptosis or necrosis) induced by the exposure to different concentrations of these heavy metals and their mixtures was evaluated in the red blood cells. Apoptosis was found to be the main type of cell death observed after cadmium and/or lead exposure. However, this exposure caused an increase in lysis or necrosis, especially if red blood cells were exposed to high doses.
Open Access
KIR3DL2 is a coinhibitory receptor on Sézary syndrome malignant T cells that promotes resistance to activation-induced cell death
(American Society of Hematology (ASH Publications), 2014-11-20) Thonnart, Nicolas; Caudron, Anne; Legaz Pérez, Isabel; Bagot, Martine; Bensussan, Armand; Cardine, Anne Marie; Ciencias Sociosanitarias
Open Access
Methods for detecting apoptotic cells in tissues
(Murcia : F. Hernández, 1997) Sanders, E.J.
In this review, methods currently available for the detection of cell death in tissues are surveyed, with special reference to techniques that allow the recognition of apoptotic cells in situ, either in whole mount specimens or in tissue sections. The techniques considered include: severa1 variations on in situ DNA nick-end labelling methods, vital dyes, lysosomal enzyme histochemistry, transglutaminase expression, and immunocytochemical detection of severa1 deathassociated antigens. These methods are discussed in relation to their utility in detecting different stages of cell death, and also to their ability to distinguish between apoptotic and necrotic cell death.
Open Access
MIR376 family and cancer
(Universidad de Murcia. Departamento de Biología Celular e Histología, 2016) Tekirdag, Kumsal Ayse; Akkoc, Yunus; Kosar, Ali; Gozuacik, Devrim
MicroRNAs (miRNAs) are endogenous noncoding small RNAs that negatively regulate gene expression at the post-transcriptional level. They have been implicated in several fundamental biological processes including development, differentiation, apoptosis and stem cell maintenance. There is increasing evidence that microRNAs also play roles in cellular transformation and carcinogenesis by acting either as tumor suppressors or oncogenes. Recent studies introduced MIR376 as an important microRNA family for cancer formation and progression. The MIR376 family is located on human chromosome 14 and it has several members containing identical or similar seed sequences. Biological roles of family members were studied in different cancer settings, including gliomas, leukemia, breast and ovarian cancers. Furthermore, two MIR376 family members, namely MIR376A and MIR376B were implicated in the regulation of macroautophagy (autophagy herein). Since autophagy dysregulation underlies various diseases including cancer, it is essential to understand the role of the MIR376 family in this context. In this article, we summarize the miRNA-cancer connection, and review accumulating data about the involvement of the MIR376 family in cancer biology.
Embargo
Mitochondrial damage as death inducer in heart-derived H9c2 cells: more than one way for an early demise
(Springer, 2009-09-24) Lax Pérez, Antonio Manuel; Soler, Fernando; Fernandez Belda, Francisco; Medicina
The release of cytochrome c from mitochondria induced by 10 microM thapsigargin was linked to rapid loss of the mitochondrial membrane potential whereas that induced by 50 nM staurosporine was mediated by Bax activation and occurred in polarized mitochondria. Similar levels of cytochrome c were observed when induced by either thapsigargin or staurosporine indicating that the release magnitude was independent of the mechanism involved in membrane permeabilization. In any case caspase 3 activation was subsequent to cytochrome c release. Mitochondrial dysfunction and release of cytochrome c occurred earlier when induced by thapsigargin even though morphological alteration of the cell and chromatin condensation were developed earlier in the presence of staurosporine. In addition, a general and irreversible caspase inhibitor did not protect against chromatin condensation induced by staurosporine. It is also shown that earlier mitochondrial damage does not always correlate with earlier cell demise. This can be attributed to the existence of alternative caspase-independent cell death programmes.
Open Access
Pyroptosis and Redox Balance in Kidney Diseases
(Mary Ann Liebert, Inc. Publishers, 2021-06-09) Cuevas, Santiago; Pelegrin, Pablo; Bioquímica y Biologia Molecular B e Inmunologia
Significance: Kidney diseases remain a worldwide public health problem resulting in millions of deaths each year; they are characterized by progressive destruction of renal function by sustained inflammation. Pyroptosis is a lytic type of programmed cell death involved in inflammation, as well as a key fibrotic mechanism that is critical in the development of kidney pathology. Pyroptosis is induced by the cleavage of Gasdermins by various caspases and is executed by the insertion of the N-terminal fragment of cleaved Gasdermins into the plasma membrane, creating oligomeric pores and allowing the release of diverse proinflammatory products into the extracellular space. Inflammasomes are multiprotein complexes leading to the activation of caspase-1, which will cleave Gasdermin D, releasing several proinflammatory cytokines; this results in the initiation and amplification of the inflammatory response. Recent Advances: The efficacy of Gasdermin D cleavage is reduced by a change in the redox balance. Recently, several studies have shown that the attenuation of reactive oxygen species (ROS) production induced by antioxidant pathways results in a reduction of renal pyroptosis. In this review, we discuss the role of pyroptosis in the pathogenesis of chronic kidney disease (CKD) and acute kidney disease; summarize the clinical outcomes and different molecular mechanisms leading to Gasdermin activation; and examine studies about the capacity of antioxidants, particularly Nrf2 activators, to ameliorate Gasdermin activity. Future Directions: We illustrate the potential influence of the deregulation of redox balance on inflammasome activity and pyroptosis as a novel therapeutic approach for the treatment of kidney diseases.
Open Access
Rosmarinic acid inhibits the proliferation of ovarian carcinoma cells by activating the p53/BAX signaling pathway
(Universidad de Murcia, Histología e Histopatología, 2025) Özdemır İlhan; Doğan Baş Dilek; Öztürk Şamil; Karaosmanoğlu Özge; Cudi Tuncer Mehmet; Biología Celular e Histología
Objective. While chemotherapeutic agents stop the development of cancer cells, they also kill healthy cells. This study aimed to increase anticancer effects and reduce side effects by combining a phytotherapeutic compound with a chemotherapeutic drug. Methods. This study examined the effects of nine concentrations of rosmarinic acid (RA) and doxorubicin (DOX) on human ovarian adenocarcinoma (OVCAR3) and skin keratinocyte (HaCaT) cell lines. Their cytotoxic effects were assessed based on cell viability, evaluated using the MTT assay, and apoptotic activity, evaluated using NucBlue staining and the gene and protein expression of tumor protein p53 (TP53) and BCL2 associated X, apoptosis regulator (BAX) quantified by qRT-PCR and western blots, respectively. Results. The half-maximal inhibitory concentration after 48 hours was 880.4 μM for RA and 2.26 μM for DOX. The cytotoxicity analysis revealed that cell viability decreased with the RA concentration. RA increased apoptosis in OVCAR3 cells by activating the p53/BAX pathway. Western blots showed that RA and DOX upregulated p53 and BAX protein levels in OVCAR3 cells. Conclusions. The RA and DOX combination inhibited cell proliferation by inducing apoptosis in OVCAR3 cells. These results suggest that RA may reduce the side effects of DOX toxicit
Open Access
The role of mitochondrial fusion and fission in the process of cardiac oxidative stress
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2020) Yu, Fei; Abdelwahid, Eltyeb; Xu, Tao; Hu, Longgang; Wang, Man; Li, Yuzhen; Mogharbel, Bassam Felipe; Teixeira de Carvalho, Katherine Athayde; Guarita-Souza, Luiz Cesar; An, Yi; Li, Peifng
Summary. Mitochondria are the energy suppliers in the cell and undergo constant fusion and fission to meet metabolic demand during the cell life cycle. Well- balanced mitochondrial dynamics are extremely important and necessary for cell survival as well as for tissue homeostasis. Cardiomyocytes contain large numbers of mitochondria to satisfy the high energy demand. It has been established that deregulated processes of mitochondrial dynamics play a major role in myocardial cell death. Currently, cardiac mitochondrial cell death pathways attract great attention in the cell biology and regenerative medicine fields. Importantly, mitochondrial dynamics are tightly linked to oxidative stress-induced cardiac damage. This review summarizes molecular mechanisms of mitochondrial fusion and fission processes and their potential roles in myocardial cell death triggered by oxidative stress. Advances in understanding the effect of both normal and abnormal mitochondrial dynamics on heart protection will lead to significant improvement of therapeutic discoveries
Open Access
The total electric charge and time of application of galvanic currents to macrophages can optimize the release of IL-1β with low cell death
(Nature Research, 2024-12-28) Peñín Franc, Alejandro; García Vidal, José Antonio; Gómez, Ana Isabel; Escolar Reina, Pilar; Medina Mirapeix, Francesc; Pelegrín, Pablo; Fisioterapia
Galvanic current has been emerging as a novel therapy to regenerate chronic tissue lesions, including musculoskeletal and dermatological lesions. Recently, the NLRP3 inflammasome and IL-1β release have been identified as a signaling pathway triggered upon galvanic current application. However, the parameters for the clinical application of galvanic current remain subjective to the experience of the facultative in charge. In this study we used an in vitro model of macrophage culture and application of different combinations of the parameters of galvanic current to study IL-1β production and cell death. Increasing electric charge of galvanic current induces the release of IL-1β, but electric charges equal or higher to 144 mC also increase cell death. The release of IL-1β have a substantial variation within different electric charge of galvanic currents, being increased by decreasing the current and increasing the time of current application. Within the range of current intensities studied, the most optimal protocol for maximizing IL-1β release without inducing cell death was identified at electric charges equal to or near 144 mC, applied over a total duration of approximately 25 s. Our findings lay the groundwork for future in vivo studies assessing different electric charge of galvanic current, with the aim of yielding clinically relevant outcomes.
Open Access
Tumor cell "dead or alive": Caspase and survivin regulate cell death, cell cycle and cell survival
(Murcia : F. Hernández, 2001) Suzuki, A.; Shiraki, K.
Cell death and cell cycle progression are two sides of the same coin, and these two different phenomenons are regulated moderately to maintain the cellular homeostasis. Tumor is one of the disease states produced as a result of the disintegrated regulation and is characterized as cells showing an irreversible progression of cell cycle and a resistance to cell death signaling. Severa1 investigations have been performed for the understanding of cell death or cell cycle, and cell death research has remarkably progressed in these 10 years. Caspase is a nomenclature referring to ICEICED- 3 cysteine proteinase family and plays a central role during cell death. Recently, severa1 investigations raised some possible hypotheses that caspase is also involved in cell cycle regulation. In this issue, therefore, we review the molecular basis of cell death and cell cycle regulated by caspase in tumor, especially hepatocellular carcinoma cells.
Open Access
β-lapachone induced cell death in human hepatoma (HepA2) cells
(F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología, 1998) Lai, C.C.; Liu, T. J.; Ho, L. K.; Don, M. J.; Chau, Y. P.
In present study we studied the cytotoxic effects of B-lapachone, a potent anticancer drug, on the human hepatoma cell line (HepA2) under serum-free condition. Most cells died after 2 ,uM B-Iapachone addition at 48 hours. No apoptotic characteristics of DNA ladder was documented by agarose DNA electrophoresis. The blockage of cell cycle at S phase and unscheduled DNA synthesis were demonstrated by flow cytometric analysis and anti-bromodeoxyuridine immunocytochemistry. Ultrastructural observation showed that the swollen mitochondria, dilatation and vesiculation of rER and proliferation of peroxisome-like granules appeared within the cytoplasm of HepA2 cells following drug treatment. Using enzyme cytochemistry, both peroxidase and acid phosphatase activities but not catalase activity were localised in these peroxisome-like granules. Therefore, these results suggested that (a) 13- lapachone has a novel cytotoxic effect on human hepatoma cell; (2) B-lapachone induces the interruption of the cell cycle and unscheduled DNA synthesis in HepA2 cells; and (3) B-lapachone promotes the proliferation of peroxisome-like granules containing peroxidase and acid phosphatase activities without evidence of catalase activity in hepatoma cell line.