scholarly journals Secondary Metabolites from Saccharomyces cerevisiae Species with Anticancer Potential

2021 ◽  
Author(s):  
Muhammad Jahangeer ◽  
Areej Riasat ◽  
Zahed Mahmood ◽  
Muhammad Numan ◽  
Naveed Munir ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Secondary Metabolites ◽  
Apoptotic Cell ◽  
Inhibitory Effect ◽  
Chemotherapeutic Agents ◽  
Chemotherapeutic Drugs ◽  
Central Metabolism ◽  
Biotic Stresses ◽  
Micro Organisms ◽  
New Chemotherapeutic Agents

Chemotherapeutic agents produce from numerous sources such as animals, plants and micro-organisms are derived from the natural products. Although the existing therapeutic pipeline lacks fungal-derived metabolites, but hundreds of secondary metabolites derived from fungi are known to be possible chemotherapies. Over the past three decades, several secondary metabolites such as flavonoids, alkaloids, phenolic and polyketides have been developed by Saccharomyces cerevisiae species with exciting activities that considered valued for the growth of new chemotherapeutic agents. Many secondary metabolites are protective compounds which prevent abiotic and biotic stresses, i.e. predation, infection, drought and ultraviolet. Though not taking part in a living cell’s central metabolism, secondary metabolites play an important role in the function of an organism. Nevertheless, due to slow biomass build-up and inadequate synthesis by the natural host the yield of secondary metabolites is low by direct isolation. A detailed comprehension of biosynthetic pathways for development of secondary metabolites are necessary for S. cerevisiae biotransformation. These metabolites have higher inhibitory effect, specificity among cancer and normal cells, and the mechanism of non-apoptotic cell killing. This study shows the significance of bioactive compounds produced by S. cerevisiae species with their possible activity and value in chemotherapeutic drugs pipeline. The isolation and alteration of these natural secondary metabolites would promote the development of chemotherapeutic drugs.

scholarly journals SYNERGISTIC GROWTH INHIBITORY EFFECT OF FLAVONOL–KAEMPFEROL AND CONVENTIONAL CHEMOTHERAPEUTIC DRUGS ON CANCER CELLS

2017 ◽  
Vol 9 (2) ◽  
pp. 123 ◽  
Author(s):  
Chepuri Kalyani ◽  
Mangamoori Lakshmi Narasu ◽  
Yumnum Priyadarshini Devi
Keyword(s):  
Growth Inhibition ◽  
Cancer Cells ◽  
Cell Line ◽  
Cell Lines ◽  
Apoptotic Cell ◽  
Inhibitory Effect ◽  
Chemotherapeutic Drugs ◽  
Growth Inhibitory Effect ◽  
Growth Inhibitory

<p><strong>Objective: </strong>The objective of the present study was to evaluate synergistic growth inhibitory effect of a flavonol, kaempferol in combination with chemotherapeutic drugs doxorubicin or cisplatin.</p><p><strong>Methods: </strong>The anti-proliferative activities of kaempferol, doxorubicin and cisplatin on human colorectal cancer cells (HCT-15) and human breast cancer (MDA MB 231) were analyzed by 3-(4,5-dimehylthiaol-2-yl)-2,5-diphenyltetraolium bromide (MTT) assay. Further, combinational studies were performed in both the cell lines to evaluate the interaction of drugs with kaempferol. The combination index (CI) method was used to assess the synergism of kaempferol with doxorubicin or cisplatin. Finally, morphological alterations associated with apoptosis were examined under fluorescent microscope.</p><h1>Results: All compounds showed dose-dependent growth inhibition in both HCT-15 and MDA MB 231 cells. The phytochemical kaempferol showed fifty percent inhibitory concentrations (IC<sub>50</sub>) at 120±3.2 µg/ml and 64±1.2 µg/ml on HCT-15 and MDA MB 231 respectively. IC<sub>50 </sub>concentrations of doxorubicin and cisplatin on both the cell lines were achieved at 49.6±0.5 µg/ml, 25.4±2.9 µg/ml and 44±1.8 µg/ml, 40.6±0.8 µg/ml respectively. Further, <em>in vitro </em>therapeutic effect (IC<sub>50</sub>) of doxorubicin and cisplatin in terms of cell growth inhibition on HCT-15 cells were achieved at their one-fifth (10±0.83 µg/ml) and half (10±1.34 µg/ml) concentrations respectively when they were combined with 30 µg/ml of kaempferol individually. Simultaneously, on MDA-MB 231 cell line, the IC<sub>50</sub> concentrations were reduced to 18±1.22 µg/ml and 15±1.87 µg/ml respectively in combination with 32 µg/ml of kaempferol. The combinational index studies revealed the synergistic association of kaempferol with doxorubicin and cisplatin individually in each cell line. The fluorescence imaging studies strongly supported the synergistic association between kaempferol and doxorubicin or cisplatin by confirming significant apoptotic cell death in both the cell lines which was ~3 fold higher than each agent alone.</h1><p><strong>Conclusion: </strong>The study reveals<strong> </strong>the prominent synergism between the phytochemical, kaempferol and chemotherapeutic drugs doxorubicin or cisplatin which helps in elevating the therapeutic efficacy of drugs.</p>

Prostatic Acid Phosphatase (PAP) Differentiated Ultracytochemically from Lysosomal Acid Phosphate in the Rat with a PAP/Specific Substrate, Phosphorylcholine

1975 ◽  
Vol 33 ◽  
pp. 450-451
Author(s):  
W. Allen Shannon ◽  
José A. Serrano ◽  
Hannah L. Wasserkrug ◽  
Anna A. Serrano ◽  
Arnold M. Seligman
Keyword(s):  
Acid Phosphatase ◽  
Phosphate Buffer ◽  
Prostatic Carcinoma ◽  
Prostatic Acid Phosphatase ◽  
Chemotherapeutic Agents ◽  
Specific Substrate ◽  
Acid Phosphate ◽  
Lysosomal Acid ◽  
Design And Synthesis ◽  
New Chemotherapeutic Agents

During the design and synthesis of new chemotherapeutic agents for prostatic carcinoma based on phosphorylated agents which might be enzyme-activated to cytotoxicity, phosphorylcholine, [(CH3)3+NCH2CH2OPO3Ca]Cl-, has been indicated to be a very specific substrate for prostatic acid phosphatase (PAP). This phenomenon has led to the development of specific histochemical and ultracytochemical methods for PAP using modifications of the Gomori lead method for acid phosphatase. Comparative histochemical results in prostate and kidney of the rat have been published earlier with phosphorylcholine (PC) and β-glycerophosphate (βGP). We now report the ultracytochemical results.Minced tissues were fixed in 3% glutaraldehyde-0.1 M phosphate buffered (pH 7.4) for 1.5 hr and rinsed overnight in several changes of 0.05 M phosphate buffer (pH 7.0) containing 7.5% sucrose. Tissues were incubated 30 min to 2 hr in Gomori acid phosphatase medium (2) containing 0.1 M substrate, either PC or βGP.

Combination Therapy of Cisplatin and Other Agents for Osteosarcoma: A Review

2020 ◽  
Vol 16 ◽  
Author(s):  
Mohamad Zahid Kasiram ◽  
Hermizi Hapidin ◽  
Hasmah Abdullah ◽  
Azlina Ahmad ◽  
Sarina Sulong
Keyword(s):  
Radiation Therapy ◽  
Survival Rate ◽  
Chemotherapeutic Agents ◽  
New Combination ◽  
Rapid Progression ◽  
Combination Regimen ◽  
Chemotherapeutic Drugs ◽  
Primary Bone Tumor ◽  
Phytochemical Compounds

Background: Osteosarcoma is the most common type of primary bone tumor in children and adolescents, which is associated with rapid progression and poor prognosis. Multimodal therapy is the most common approach utilized for osteosarcoma management, such as the application of chemotherapy in combination with surgery or radiation therapy. Cisplatin is one of the predominantly used chemotherapeutic agents for osteosarcoma. Optimally, it is employed in combination with other chemotherapeutic drugs along with surgery or radiation therapy. Despite the availability of numerous treatment approaches, patient survival rate has not definitively improved over the past three decades. Methods: We summarized all findings regarding the combination of cisplatin with other chemotherapeutic agents as well as with phytochemical compounds. Results: A combination of cisplatin with phytochemical compound synergistically enhances the killing effect of cisplatin on osteosarcoma cells with fewer side effects compared to combination with other chemotherapeutic agents. Conclusion: Conclusively, a combination of cisplatin with selected chemotherapeutic drugs, has been shown to be effective. However, the unchanged survival rate urges for the search of a new combination regimen. As a collaborative effort to substantiate the therapeutic efficacy, the combination with phytochemical compounds shows a promising response both in vitro as well as in the preclinical study.

Inhibition of Yeast Growth by Tryptamine and Recovery with Tryptophan

2020 ◽  
Vol 16 (1) ◽  
pp. 48-52 ◽  
Author(s):  
Chandrika Kadkol ◽  
Ian Macreadie
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Carbon Source ◽  
Competitive Inhibition ◽  
Yeast Species ◽  
Inhibitory Effect ◽  
The Body ◽  
Inhibitory Effects ◽  
Trna Synthetases ◽  
Fermentative Growth ◽  
Biogenic Monoamine

Background: Tryptamine, a biogenic monoamine that is present in trace levels in the mammalian central nervous system, has probable roles as a neurotransmitter and/or a neuromodulator and may be associated with various neuropsychiatric disorders. One of the ways tryptamine may affect the body is by the competitive inhibition of the attachment of tryptophan to tryptophanyl tRNA synthetases. Methods: This study has explored the effects of tryptamine on growth of six yeast species (Saccharomyces cerevisiae, Candida glabrata, C. krusei, C. dubliniensis, C. tropicalis and C. lusitaniae) in media with glucose or ethanol as the carbon source, as well as recovery of growth inhibition by the addition of tryptophan. Results: Tryptamine was found to have an inhibitory effect on respiratory growth of all yeast species when grown with ethanol as the carbon source. Tryptamine also inhibited fermentative growth of Saccharomyces cerevisiae, C. krusei and C. tropicalis with glucose as the carbon source. In most cases the inhibitory effects were reduced by added tryptophan. Conclusion: The results obtained in this study are consistent with tryptamine competing with tryptophan to bind mitochondrial and cytoplasmic tryptophanyl tRNA synthetases in yeast: effects on mitochondrial and cytoplasmic protein synthesis can be studied as a function of growth with glucose or ethanol as a carbon source. Of the yeast species tested, there is variation in the sensitivity to tryptamine and the rescue by tryptophan. The current study suggests appropriate yeast strains and approaches for further studies.

Malignant mesothelioma: In vitro responses to new chemotherapeutic agents, and correlation to GSTM1 and NAT2 gene polymorphism

1997 ◽  
Vol 33 ◽  
pp. S175
Author(s):  
K. Mattson ◽  
T. Ollikainen ◽  
A. Hirvonen ◽  
M. Halme ◽  
A. Knuuttila ◽  
...  
Keyword(s):  
Gene Polymorphism ◽  
Malignant Mesothelioma ◽  
Chemotherapeutic Agents ◽  
Nat2 Gene ◽  
New Chemotherapeutic Agents

scholarly journals A novel radiolytic rotenone derivative, rotenoisin A, displays potent anticarcinogenic activity in breast cancer cells

2021 ◽  
Author(s):  
Dong-ho Bak ◽  
Seong Hee Kang ◽  
Chul-hong Park ◽  
Byung Yeoup Chung ◽  
Hyoung-Woo Bai
Keyword(s):  
Breast Cancer ◽  
Adverse Effects ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Parent Compound ◽  
Inhibitory Effect ◽  
Chemotherapeutic Agents ◽  
Epidermal Keratinocytes ◽  
Functional Changes ◽  
Structural Modifications

Abstract Chemotherapy for cancer treatment has therapeutic limitations, such as drug resistance, excessive toxic effects and undesirable adverse effects. Therefore, efforts to improve the safety and efficacy of chemotherapeutic agents are essential. Ionizing radiation can improve physiological and pharmacological properties by transforming structural modifications of the drug. In this study, in order to reduce the adverse effects of rotenone and increase anticancer activity, a new radiolytic rotenone derivative called rotenoisin A was generated through radiolytic transformation. Our findings showed that rotenoisin A inhibited the proliferation of breast cancer cells and increased the rate of apoptosis, whereas it had no inhibitory effect on primary epidermal keratinocytes compared with rotenone. Moreover, rotenoisin A-induced DNA damage by increasing reactive oxygen species (ROS) accumulation. It was also confirmed not only to alter the composition ratio of mitochondrial proteins, but also to result in structural and functional changes. The anticancer effect and molecular signalling mechanisms of rotenoisin A were consistent with those of rotenone, as previously reported. Our study suggests that radiolytic transformation of highly toxic compounds may be an alternative strategy for maintaining anticancer effects and reducing the toxicity of the parent compound.

Role of cations in the flocculation of Saccharomyces cerevisiae and discrimination of the corresponding proteins

1991 ◽  
Vol 37 (5) ◽  
pp. 397-403 ◽  
Author(s):  
Hiroshi Kuriyama ◽  
Itaru Umeda ◽  
Harumi Kobayashi
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Surface ◽  
Inhibitory Effect ◽  
Surface Proteins ◽  
Promoting Effect ◽  
Yeast Strains ◽  
Yeast Flocculation ◽  
Different Types ◽  
Anionic Groups

Asexual yeast flocculation was studied using strong flocculents of Saccharomyces cerevisiae. The inhibitory effect of cations on flocculation is considered to be caused by competition between those cations and Ca2+ at the binding site of the Ca2+-requiring protein that is involved in flocculation. Inhibition of flocculation by various cations occurred in the following order: La3+, Sr2+, Ba2+, Mn2+, Al3+, and Na+. Cations such as Mg2+, Co2+, and K+ promoted flocculation. This promoting effect may be based on the reduction of electrostatic repulsive force between cells caused by binding of these cations anionic groups present on the cell surface. In flocculation induced by these cations, trace amounts of Ca2+ excreted on the cell surface may activate the corresponding protein. The ratio of Sr2+/Ca2+ below which cells flocculated varied among strains: for strains having the FLO5 gene, it was 400 to 500; for strains having the FLO1 gene, about 150; and for two alcohol yeast strains, 40 to 50. This suggests that there are several different types of cell surface proteins involved in flocculation in different yeast strains. Key words: yeast, flocculation, protein, cation, calcium.

scholarly journals Saccharomyces cerevisiae Grx6 and Grx7 Are Monothiol Glutaredoxins Associated with the Early Secretory Pathway

2008 ◽  
Vol 7 (8) ◽  
pp. 1415-1426 ◽  
Author(s):  
Alicia Izquierdo ◽  
Celia Casas ◽  
Ulrich Mühlenhoff ◽  
Christopher Horst Lillig ◽  
Enrique Herrero
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Active Site ◽  
Secretory Pathway ◽  
Transmembrane Domain ◽  
Inhibitory Effect ◽  
Protein Accumulation ◽  
Oxidoreductase Activity ◽  
Early Secretory Pathway ◽  
Glycosylation Inhibitor

ABSTRACT Saccharomyces cerevisiae Grx6 and Grx7 are two monothiol glutaredoxins whose active-site sequences (CSYS and CPYS, respectively) are reminiscent of the CPYC active-site sequence of classical dithiol glutaredoxins. Both proteins contain an N-terminal transmembrane domain which is responsible for their association to membranes of the early secretory pathway vesicles, facing the luminal side. Thus, Grx6 localizes at the endoplasmic reticulum and Golgi compartments, while Grx7 is mostly at the Golgi. Expression of GRX6 is modestly upregulated by several stresses (calcium, sodium, and peroxides) in a manner dependent on the Crz1-calcineurin pathway. Some of these stresses also upregulate GRX7 expression under the control of the Msn2/4 transcription factor. The N glycosylation inhibitor tunicamycin induces the expression of both genes along with protein accumulation. Mutants lacking both glutaredoxins display reduced sensitivity to tunicamycin, although the drug is still able to manifest its inhibitory effect on a reporter glycoprotein. Grx6 and Grx7 have measurable oxidoreductase activity in vivo, which is increased in the presence of tunicamycin. Both glutaredoxins could be responsible for the regulation of the sulfhydryl oxidative state at the oxidant conditions of the early secretory pathway vesicles. However, the differences in location and expression responses against stresses suggest that their functions are not totally overlapping.

scholarly journals Adaptation of central metabolite pools to variations in growth rate and cultivation conditions in Saccharomyces cerevisiae

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Kanhaiya Kumar ◽  
Vishwesh Venkatraman ◽  
Per Bruheim
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Growth Rate ◽  
Amino Acid ◽  
Growth Rates ◽  
Pentose Phosphate Pathway ◽  
Pentose Phosphate ◽  
Relative Reduction ◽  
Central Metabolism ◽  
Cultivation Conditions ◽  
Biological Studies

Abstract Background Saccharomyces cerevisiae is a well-known popular model system for basic biological studies and serves as a host organism for the heterologous production of commercially interesting small molecules and proteins. The central metabolism is at the core to provide building blocks and energy to support growth and survival in normal situations as well as during exogenous stresses and forced heterologous protein production. Here, we present a comprehensive study of intracellular central metabolite pool profiling when growing S. cerevisiae on different carbon sources in batch cultivations and at different growth rates in nutrient-limited glucose chemostats. The latest versions of absolute quantitative mass spectrometry-based metabolite profiling methodology were applied to cover glycolytic and pentose phosphate pathway metabolites, tricarboxylic acid cycle (TCA), complete amino acid, and deoxy-/nucleoside phosphate pools. Results Glutamate, glutamine, alanine, and citrate were the four most abundant metabolites for most conditions tested. The amino acid is the dominant metabolite class even though a marked relative reduction compared to the other metabolite classes was observed for nitrogen and phosphate limited chemostats. Interestingly, glycolytic and pentose phosphate pathway (PPP) metabolites display the largest variation among the cultivation conditions while the nucleoside phosphate pools are more stable and vary within a closer concentration window. The overall trends for glucose and nitrogen-limited chemostats were increased metabolite pools with the increasing growth rate. Next, comparing the chosen chemostat reference growth rate (0.12 h−1, approximate one-fourth of maximal unlimited growth rate) illuminates an interesting pattern: almost all pools are lower in nitrogen and phosphate limited conditions compared to glucose limitation, except for the TCA metabolites citrate, isocitrate and α-ketoglutarate. Conclusions This study provides new knowledge-how the central metabolism is adapting to various cultivations conditions and growth rates which is essential for expanding our understanding of cellular metabolism and the development of improved phenotypes in metabolic engineering.

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