Stopped Cell Growth Research Articles

Inhibitors of the mTOR signaling pathway can play an important role in breast cancer immunopathogenesis.

This study explores the critical role of inhibitors targeting the mammalian target of rapamycin (mTOR) signaling pathway in breast cancer research and treatment. The mTOR pathway, a central regulator of cellular processes, has been identified as a crucial factor in the development and progression of breast cancer. The essay explains the complex molecular mechanisms through which mTOR inhibitors, such as rapamycin and its analogs, exert their anticancer effects. These inhibitors can stop cell growth, proliferation, and survival in breast cancer cells by blocking critical signaling pathways within the mTOR pathway. Furthermore, the essay discusses the implications of using mTOR inhibitors as a comprehensive therapeutic strategy. It emphasizes the potential benefits of combining mTOR inhibitors with other treatment approaches to enhance the effectiveness of breast cancer treatment. The evolving landscape of breast cancer research underscores the significance of mTOR as a therapeutic target and highlights ongoing efforts to improve and optimize mTOR inhibitors for clinical use. In conclusion, the essay asserts that inhibitors of the mTOR signaling pathway offer a promising approach in the fight against breast cancer. These inhibitors provide a focused and effective intervention targeting specific dysregulations within the mTOR pathway. As research advances, the integration of mTOR inhibitors into customized combination therapies holds excellent potential for shaping a more effective and personalized approach to breast cancer treatment, ultimately leading to improved outcomes for individuals affected by this complex and diverse disease.

THE ANTITUMOR ACTIVITY OF ARALOSIDE A FROM ARALIA ELATA ROOT BARK IN HUMAN KIDNEY CANCER CELLS

The root bark of Aralia elata is the source of araloside A, which has attracted interest because to its possible therapeutic benefits on human kidney cancer cells. This study examines our current knowledge of the mechanisms of action of araloside A and how it affects many facets of the physiology of kidney cancer cells. It is detailed how the substance can cause apoptosis, stop cell growth, and obstruct signaling pathways that are essential for the development of cancer. Furthermore, new experimental results are used to assess its safety and efficacy profiles. To fully utilize Araloside A's therapeutic potential in the treatment of kidney cancer, future research approaches are suggested.

A Narrative Review of Current Knowledge on Cutaneous Melanoma.

Cutaneous melanoma is a public health problem. Efforts to reduce its incidence have failed, as it continues to increase. In recent years, many risk factors have been identified. Numerous diagnostic systems exist that greatly assist in early clinical diagnosis. The histopathological aspect illustrates the grim nature of these cancers. Currently, pathogenic pathways and the tumor microclimate are key to the development of therapeutic methods. Revolutionary therapies like targeted therapy and immune checkpoint inhibitors are starting to replace traditional therapeutic methods. Targeted therapy aims at a specific molecule in the pathogenic chain to block it, stopping cell growth and dissemination. The main function of immune checkpoint inhibitors is to boost cellular immunity in order to combat cancer cells. Unfortunately, these therapies have different rates of effectiveness and side effects, and cannot be applied to all patients. These shortcomings are the basis of increased incidence and mortality rates. This study covers all stages of the evolutionary sequence of melanoma. With all these data in front of us, we see the need for new research efforts directed at therapies that will bring greater benefits in terms of patient survival and prognosis, with fewer adverse effects.

(Invited) Using the Model Bacterium Geobacter Sulfurreducens to Understand Microbial Electrochemical Conversion of Nitrogen Gas into Ammonium

There is a growing need to decrease reliance on the Haber-Bosch process. To convert nitrogen gas (N2) into ammonia (NH3) for fertilizers, this temperature- and pressure-intensive process consumes roughly 2–3% of global energy and releases over 740 million tons of CO2 each year. Many microorganisms naturally convert or “fix” N2 into ammonium (NH4 +) at room temperature and pressure using an enzyme called the nitrogenase. Attempts to increase NH4 + yields from microorganisms through genetic engineering are seeing signs of success, but we lack methods to increase NH4 + generation rates and overcome one of the largest challenges: O2 gas. Increasing O2 gas concentrations typically increases metabolic rates of aerobic microorganisms; however, in the case of microorganisms that fix N2 (called diazotrophs), O2 can shut down the nitrogenase and stop cell growth. To overcome these challenges, we are using electricity to drive N2 fixation in exoelectrogenic bacteria. These bacteria have the unique ability to naturally transfer electrons to anode electrodes in microbial electrochemical technologies (METs). Increasing the voltage applied to METs increases the metabolic rates of exoelectrogens. The anode chamber is kept anaerobic, which eliminates O2-driven inhibition of the nitrogenase. We previously showed that the N2 fixation rates of a mixed microbial community in a MET increased more than three times when the applied whole-cell potential increased from 0.7 V to 1.0 V. By adding a chemical inhibitor that prevented the incorporation of NH4 + into larger biomolecules, NH4 + was excreted by the cells and into the medium. Based on the acetylene reduction assay (a proxy for N2 fixation), we estimated that we recovered about 10% of the theoretical NH4 +generated by the cells. If close to 100% of the theoretical NH4 + could be excreted from the cells and recovered, we predicted an energy demand of around 3 MJ/mol-NH4 +, which is close to the range of value reported for the Haber-Bosch process. To develop METs that generate NH4 + at competitive production rates and energy demands, we are now focusing on the model exoelectrogenic diazotroph Geobacter sulfurreducens. Using a single organism with a fully sequenced genome allows us to understand how the N2 fixation process responds to electrochemical variables. Towards these efforts, we conducted a transcriptomic analysis of G. sulfurreducens at two fixed anode potentials: +0.15 V and −0.15 V. This approach revealed which genes are turned on and off in response to these potentials. The presence of NH4 + decreased the expression of genes associated with N2 fixation which was expected due to the known sensitivity of nitrogenases to NH4 +. On the other hand, the two anode potentials had a dramatic and unexpected impact on the expression levels of N2 fixation genes. At −0.15 V, nitrogenase genes were significantly up-regulated, as were genes associated with NH4 + uptake and transport, such as glutamine and glutamate synthetases. Considering that −0.15 V provides less energy to the cells relative to +0.15 V (based on thermodynamic predictions), the results suggest that the cells responded to this highly energy-constrained environment by increasing expression of N2 fixation pathways. Based on our new knowledge of how G. sulfurredcuens regulates N2 fixation and NH4 + production, we have developed new strains of G. sulfurreducens that can excrete NH4 + during N2 fixation. The new engineering toolkit that we have created in this bacterium can now be leveraged to maximize NH4 + production in METs.

Development of venetoclax performance using its new derivatives on BCL-2 protein inhibition.

Cancer cells are resistant to apoptosis and this is one of the most obvious symptoms of cancer in humans. One of the most exciting strategies for treating cancer is to design regulators that increase cell death and stop cell growth. Members of the BCL-2 family of proteins play an important role in the regulation of apoptosis. In this study, an attempt was made to improve the performance of one of the anticancer drugs by designing new analogs of venetoclax (VNT). For this purpose, molecular docking studies were performed to determine the best binding state of VNT and its newly designed derivatives at the protein-binding site to estimate the binding energy. The best analog in terms of free energy was VNT-12 with the lowest energy (-12.15 kcal/mol). Finally, to investigate the inhibitory effect of the compounds on BCL-2 protein, molecular dynamics simulation was used, and by performing the relevant analyses during the simulation, it was observed that the newly designed ligand had better performance in inhibiting BCL-2 protein compared to VNT.

DETERMINATION OF THE SYNERGISTIC EFFECT OF CURCUMIN AND CARNOSIC ACID ON THE PROLIFERATION OF PROSTATE CANCER CELLS

Relevance: Cancer is one of the leading causes of death globally. The results of the conducted studies on the energy metabolism of
 cancer cells can contribute to identifying molecular targets in the treatment of cancer. It is known that polyphenols widely distributed in
 plants have an anti-cancer effect based on their well-known antioxidant, anti-inflammatory, antiproliferative, proapoptotic, and antiangiogenic potential.
 Primary prostate cancer treatment methods include surgical resection and chemo- or radiation therapy. In the last decade, polyphenols
 have attracted attention for use in complex prostate cancer chemotherapy. The search for natural compounds increasing the body’s resistance to tumor development and reducing the possibility of tumor recurrence after radiation or chemotherapy and studying their mechanisms of action are relevant directions for further in vivo research. In addition, there is a growing interest in studying practical treatment
 approaches combining drugs with various mechanisms of action.
 The study aimed to identify the synergistic effect of curcumin and carnosic acid on the proliferation of prostate cancer cells.
 Methods: The proliferative activity of cells in culture on tablets, under the influence of polyphenols in various concentrations, was
 evaluated by Alamar blue using a BioTek Synergy plate reader (BD Biosciences, San Jose, CA).
 Results: При In determining the effect of naturally occurring polyphenols on prostate cancer cell proliferation, the effect of curcumin
 was significantly greater than that of carnosic acid. In a higher concentration, their effect on the proliferation of prostate cancer cells was
 higher and stopped cell growth by 30-60%, depending on the concentration and time of exposure.
 Conclusion: A detailed evaluation of the data on inhibition of PC3, Du145 cell growth revealed a clear synergistic interaction between
 curcumin and carnosic acid, which was especially strong at a concentration of curcumin 7 μM in combination with carnosic acid 5 μM

RETRACTED ARTICLE: Overexpression of CCN1 in esophageal squamous cell carcinoma attenuates cell proliferation through amyloid precursor protein without DR6 involvement.

Esophageal cancer is commonly seen as either squamous cell carcinoma (ESCC) or adenocarcinoma (EAC), two very different cancers. CCN1 is a matricellular protein that induces apoptosis in EAC cells through upregulation of DR5, a death receptor, while its role in ESCC is unclear. DR6 is another death receptor, which has been reported to induce apoptosis, necroptosis, or pyroptosis in various cell systems with or without the engagement of its putative ligand amyloid precursor protein (APP). In this study, we found that CCN1 and DR6 were both highly expressed in ESCC but downregulated in EAC. Overexpression of CCN1 in ESCC cells induced cell cycle arrest rather than apoptosis through upregulation of APP and its association with p53 without DR6 involvement. Overexpression of APP stopped cell growth, but overexpression of DR6 did not cause any form of programmed cell death or cell cycle arrest whatsoever.

CCN1 suppresses cell proliferation of esophageal squamous cell carcinoma through amyloid precursor protein without DR6 participation

Esophageal cancer is commonly seen as either squamous cell carcinoma (ESCC) or adenocarcinoma (EAC), two very different cancers. CCN1 is a matricellular protein that induces apoptosis in EAC cells through upregulation of DR5, a death receptor, while its role in ESCC is unclear. DR6 is another death receptor, which has been reported to induce apoptosis, necroptosis, or pyroptosis in various cell systems with or without the engagement of its putative ligand amyloid precursor protein (APP). In this study, we found that CCN1 and DR6 were both highly expressed in ESCC but downregulated in EAC. Overexpression of CCN1 in ESCC cells inhibited cell proliferation through upregulation of APP and its association with p53 without DR6 involvement. Overexpression of APP stopped cell growth, but overexpression of DR6 did not affect cell growth or cell death whatsoever.

The effect of 4-hexylresocinol administration on SCC-9 cells: mass spectrometric identification of proteins and cDNA microarray analysis

BackgroundIn stress situations, bacteria produce dormancy-inducing factors to stop cell growth. The dormancy-inducing factors may have an inhibitory effect on tumor cell growth. Here we analyzed the differentially expressed protein profiles after 4-hexylresorcinol (4HR), one of the dormancy-inducing factors, administration using in vitro oral squamous carcinoma cells (SCC-9).MethodThe control group was SCC-9 cells culture without 4HR administration. The experimental group received 10 μg/mL of 4HR. Collected proteins from each group were loaded for 2D electrophoresis. Among the separated proteins, 20 differentially expressed proteins were selected and processed for LC-MS/MS.ResultsIn proteomic analysis, the expression of keratin 1, keratin 10, and histone H2B were increased. In cDNA microarray assay, the genes related to the cellular differentiation (involucrin, keratin 13, 14) were highly expressed in the 4HR treated group (fold ratio > 2.0; Table 2). Interestingly, histone family was upregulated in the cDNA microarray assay.ConclusionThe administration of 4HR on SCC-9 cells increased epithelial cell differentiation markers and histone.

Enhanced Tolerance of Spathaspora passalidarum to Sugarcane Bagasse Hydrolysate for Ethanol Production from Xylose.

During the pretreatment and hydrolysis of lignocellulosic biomass to obtain a hydrolysate rich in fermentable sugars, furaldehydes (furfural and hydroxymethylfurfural), phenolic compounds, and organic acids are formed and released. These compounds inhibit yeast metabolism, reducing fermentation yields and productivity. This study initially confirmed the ability of Spathaspora passalidarum to ferment xylose and demonstrated its sensibility to the inhibitors present in the hemicellulosic sugarcane bagasse hydrolysate. Then, an adaptive laboratory evolution, with progressive increments of hydrolysate concentration, was employed to select a strain more resistant to hydrolysate inhibitors. Afterward, a central composite design was performed to maximize ethanol production using hydrolysate as substrate. At optimized conditions (initial cell concentration of 30 g/L), S. passalidarum was able to produce 19.4 g/L of ethanol with productivity, yield, and xylose consumption rate of 0.8 g/L.h and 0.4 g/g, respectively, in a sugarcane bagasse hemicellulosic hydrolysate. A kinetic model was developed to describe the inhibition of fermentation by substrate and product. The values obtained for substrate saturation and inhibition constant were Ks = 120.4 g/L and Ki = 1293.4 g/L. Ethanol concentration that stops cell growth was 30.1 g/L. There was an agreement between simulated and experimental results, with a residual standard deviation lower than 6%.

Effect of Cadmium Ions on Some Biophysical Parameters and Ultrastructure of Ankistrodesmus sp. В-11 Cells

Effects of low concentrations of cadmium ions on growth, photosynthesis, and cell ultrastructure of microalga Ankistrodesmus sp. B-11 were investigated. The addition of cadmium to growth medium at concentrations of 0.005–0.02 mg/L led to a significant decrease in the number of Ankistrodesmus sp. B-11 cells relatively to that in the untreated culture. The addition of cadmium at concentrations >0.05 mg/L completely stopped cell growth. Cadmium ions induced ultrastructural changes in the arrangement of thylakoids within the stroma, the detachment of thylakoid membranes with the formation of void interthylakoid spaces, and a significant increase in vacuolization of microalgal cells. Simultaneous measurements of fluorescence induction curves and redox transformations of photosystem I components on a microsecond time scale by means of a M‑PEA-2 fluorometer revealed that cadmium ions inhibit electron transport in photosystem II (PSII). The quantum yield of electron transport in PSII (φEo) and the performance index (PIABS) were found to decrease; the photoreduction of P700 pigment was decelerated, while energy dissipation (DI0/RC) and ΔpH-dependent nonphotochemical quenching (qE) increased significantly under the action of cadmium. The performance index (PIABS) was the most sensitive parameter; it can be used for the detection of early toxic effects of cadmium ions on algae.

Glycolipids Recognized by A2B5 Antibody Promote Proliferation, Migration, and Clonogenicity in Glioblastoma Cells.

A2B5+ cells isolated from human glioblastomas exhibit cancer stem cell properties. The A2B5 epitope belongs to the sialoganglioside family and is synthetized by the ST8 alpha-N-acetyl-neuraminidase α-2,8-sialyltransferase 3 (ST8SIA3) enzyme. Glycolipids represent attractive targets for solid tumors; therefore, the aim of this study was to decipher A2B5 function in glioblastomas. To this end, we developed cell lines expressing various levels of A2B5 either by genetically manipulating ST8SIA3 or by using neuraminidase. The overexpression of ST8SIA3 in low-A2B5-expressing cells resulted in a dramatic increase of A2B5 immunoreactivity. ST8SIA3 overexpression increased cell proliferation, migration, and clonogenicity in vitro and tumor growth when cells were intracranially grafted. Conversely, lentiviral ST8SIA3 inactivation in low-A2B5-expressing cells resulted in reduced proliferation, migration, and clonogenicity in vitro and extended mouse survival. Furthermore, in the shST8SIA3 cells, we found an active apoptotic phenotype. In high-A2B5-expressing cancer stem cells, lentiviral delivery of shST8SIA3 stopped cell growth. Neuraminidase treatment, which modifies the A2B5 epitope, impaired cell survival, proliferation, self-renewal, and migration. Our findings prove the crucial role of the A2B5 epitope in the promotion of proliferation, migration, clonogenicity, and tumorigenesis, pointing at A2B5 as an attractive therapeutic target for glioblastomas.

THE ANTITUMOR ACTIVITY OF ARALOSIDE A FROM ARALIA ELATA ROOT BARK IN HUMAN KIDNEY CANCER CELLS

The root bark of Aralia elata is the source of araloside A, which has attracted interest because to its possible therapeutic benefits on human kidney cancer cells. This study examines our current knowledge of the mechanisms of action of araloside A and how it affects many facets of the physiology of kidney cancer cells. It is detailed how the substance can cause apoptosis, stop cell growth, and obstruct signaling pathways that are essential for the development of cancer. Furthermore, new experimental results are used to assess its safety and efficacy profiles. To fully utilize Araloside A's therapeutic potential in the treatment of kidney cancer, future research approaches are suggested.

Slowdown of Translational Elongation in Escherichia coli under Hyperosmotic Stress

ABSTRACTIn nature, bacteria frequently experience many adverse conditions, including heat, oxidation, acidity, and hyperosmolarity, which all tend to slow down if not outright stop cell growth. Previous work on bacterial stress mainly focused on understanding gene regulatory responses. Much less is known about how stresses compromise protein synthesis, which is the major driver of cell growth. Here, we quantitatively characterize the translational capacity of Escherichia coli cells growing exponentially under hyperosmotic stress. We found that hyperosmotic stress affects bacterial protein synthesis through reduction of the translational elongation rate, which is largely compensated for by an increase in the cellular ribosome content compared with nutrient limitation at a similar growth rate. The slowdown of translational elongation is attributed to a reduction in the rate of binding of tRNA ternary complexes to the ribosomes.

CP39, CP75 and CP91 are major structural components of the Dictyostelium centrosome’s core structure

The acentriolar Dictyostelium centrosome is a nucleus-associated body consisting of a core structure with three plaque-like layers, which are surrounded by a microtubule-nucleating corona. The core duplicates once per cell cycle at the G2/M transition, whereby its central layer disappears and the two outer layers form the mitotic spindle poles. Through proteomic analysis of isolated centrosomes, we have identified CP39 and CP75, two essential components of the core structure. Both proteins can be assigned to the central core layer as their centrosomal presence is correlated to the disappearance and reappearance of the central core layer in the course of centrosome duplication. Both proteins contain domains with centrosome-binding activity in their N- and C-terminal halves, whereby the respective N-terminal half is required for cell cycle-dependent regulation. CP39 is capable of self-interaction and GFP-CP39 overexpression elicited supernumerary microtubule-organizing centers and pre-centrosomal cytosolic clusters. Underexpression stopped cell growth and reversed the MTOC amplification phenotype. In contrast, in case of CP75 underexpression of the protein by RNAi treatment elicited supernumerary MTOCs. In addition, CP75RNAi affects correct chromosome segregation and causes co-depletion of CP39 and CP91, another central core layer component. CP39 and CP75 interact with each other directly in a yeast two-hybrid assay. Furthermore, CP39, CP75 and CP91 mutually interact in a proximity-dependent biotin identification (BioID) assay. Our data indicate that these three proteins are all required for proper centrosome biogenesis and make up the major structural components of core structure's central layer.

438. Oncolytic Immunotherapy for Treatment of Breast Cancer, Including Triple-Negative Breast Cancer

Breast cancer is a heterogeneous disease, characterized by several distinct biological subtypes associated with specifical biological behavior and different clinical outcomes. Triple-negative breast cancer (TNBC) is defined as estrogen receptor (ER)-negative, progesterone receptor (PR)-negative and lacking overexpression of human epidermal growth factor receptor 2 (HER2). Among all the breast cancer subtypes, TNBC (10-15% of breast cancers) is associated with a worse prognosis.Oncolytic virus replication is an immunogenic phenomenon, and viruses can be armed with immunostimulatory molecules. Cyclophosphamide (CP) is a chemotherapy drug that works by slowing or stopping cell growth. At higher doses, CP is associated with increased cytotoxicity and immunosuppression, while at low continuous dosage it shows immunostimulatory and antiangiogenic properties. Therefore, the combination of oncolytic immunovirotherapy with low-dose CP is an appealing approach.We investigated the potency of oncolytic adenovirus Ad5/3-D24-GMCSF on a TNBC cell line and animal models, in combination with low-dose CP or its main active metabolite 4-hydroxycyclophosphamide (4-HP-CP). Furthermore, we summarized the breast cancer-specific human data from the Advanced Therapy Access Program (ATAP).Low-dose CP effectively increased the efficacy of Ad5/3-D24-GMCSF in vitro and in a TNBC xenograft mouse model. In ATAP, treatments appeared safe and well-tolerated. Fourteen out of sixteen breast cancer patients treated were evaluable for possible therapy benefit with modified RECIST criteria: one patient had minor response, four had stable disease, and nine had progressive disease. One patient was alive at 941 days after treatment.Ad5/3-D24-GMCSF in combination with low-dose CP showed promising efficacy in preclinical studies and possible antitumor activity in breast cancer patients refractory to other forms of therapy. This preliminary data supports continuing the clinical development of oncolytic adenoviruses for treatment of breast cancer, including TNBC.

The dinoflagellate Lingulodinium polyedrum responds to N depletion by a polarized deposition of starch and lipid bodies.

Dinoflagellates are important contributors to the marine phytoplankton and global carbon fixation, but are also infamous for their ability to form the spectacular harmful algal blooms called red tides. While blooms are often associated with high available nitrogen, there are instances where they are observed in oligotrophic environments. In order to maintain their massive population in conditions of nitrogen limitation, dinoflagellates must have evolved efficient adaptive mechanisms. Here we report the physiological responses to nitrogen deprivation in Lingulodinium polyedrum. We find that this species reacts to nitrogen stress, as do most plants and microalgae, by stopping cell growth and diminishing levels of internal nitrogen, in particular in the form of protein and chlorophyll. Photosynthesis is maintained at high levels for roughly a week following nitrate depletion, resulting in accumulated photosynthetic products in the form of starch. During the second week, photosynthesis rates decrease due to a reduction in the number of chloroplasts and the accumulation of neutral lipid droplets. Surprisingly, the starch granules and lipid droplets are seen to accumulate at opposite poles of the cell. Lastly, we observe that cells acclimated to nitrogen-depleted conditions resume normal growth after addition of inorganic nitrogen, but are able to maintain high cell densities far longer than cells grown continuously in nitrogen-replete conditions.

Cellular stress responses in cancer and cancer therapy.

Cellular stress responses in cancer and cancer therapy.

TbKAP6, a mitochondrial HMG box-containing protein in Trypanosoma brucei, is the first trypanosomatid kinetoplast-associated protein essential for kinetoplast DNA replication and maintenance.

Kinetoplast DNA (kDNA), the mitochondrial genome of trypanosomatids, is a giant planar network of catenated minicircles and maxicircles. In vivo kDNA is organized as a highly condensed nucleoprotein disk. So far, in Trypanosoma brucei, proteins involved in the maintenance of the kDNA condensed structure remain poorly characterized. In Crithidia fasciculata, some small basic histone H1-like kinetoplast-associated proteins (CfKAP) have been shown to condense isolated kDNA networks in vitro. High-mobility group (HMG) box-containing proteins, such as mitochondrial transcription factor A (TFAM) in mammalian cells and Abf2 in the budding yeast, have been shown essential for the packaging of mitochondrial DNA (mtDNA) into mitochondrial nucleoids, remodeling of mitochondrial nucleoids, gene expression, and maintenance of mtDNA. Here, we report that TbKAP6, a mitochondrial HMG box-containing protein, is essential for parasite cell viability and involved in kDNA replication and maintenance. The RNA interference (RNAi) depletion of TbKAP6 stopped cell growth. Replication of both minicircles and maxicircles was inhibited. RNAi or overexpression of TbKAP6 resulted in the disorganization, shrinkage, and loss of kDNA. Minicircle release, the first step in kDNA replication, was inhibited immediately after induction of RNAi, but it quickly increased 3-fold upon overexpression of TbKAP6. Since the release of covalently closed minicircles is mediated by a type II topoisomerase (topo II), we examined the potential interactions between TbKAP6 and topo II. Recombinant TbKAP6 (rTbKAP6) promotes the topo II-mediated decatenation of kDNA. rTbKAP6 can condense isolated kDNA networks in vitro. These results indicate that TbKAP6 is involved in the replication and maintenance of kDNA.

Identification of New Lactone Derivatives Isolated from Trichoderma sp., An Endophytic Fungus of Brotowali (Tinaspora crispa)

Endophytic fungi is a rich source of novel organic compounds with interesting biological activities and a high level of structural diversity. As a part of our systematic search for new bioactive lead structures and specific profiles from endophytic fungi, an endophytic fungus was isolated from roots of brotowali (Tinaspora crispa), an important medicinal plant. Colonial morphological trait and microscopic observation revealed that the endophytic fungus was Trichoderma sp. The pure fungal strain was cultivated on 7 L Potatos Dextose Broth (PDB) medium under room temperature (no shaking) for 8 weeks. The ethyl acetate were added to cultur medium and left overnight to stop cell growth. The culture filtrates were collected and extracted with EtOAc and then taken to evaporation. Two new lactone derivatives, 5-hydroxy-4-hydroxymethyl-2H-pyran-2-one (1) and (5-hydroxy-2-oxo-2H pyran-4-yl) methyl acetate (2) were obtained from the EtOAc extracts of Trichoderma sp. Their structures were determined on the basic of spectroscopic methods including UV, IR, 1H-NMR, 13C-NMR, HMQC, and HMBC.