Warburg effect: cancer cells metabolism

Prva istraživanja energetskog metabolizma tumora provodila su se 1922. godine u laboratoriju Otto Warburga. Warburg je ustanovio specifičan metabolizam stanica raka čija je karakteristika prijelaz s respiracije na fermentaciju - nazvan je Warburg-ov efekt. Wrburgov efekt predstavlja glavni razlog transformacije normalnih stanica u tumorske stanice. Tumorske stanice održavaju visoku razinu glikolize, čak i u uvjetima kada je doprema kisika stanicama dostatna, te akumuliraju velike količine laktata. Smatra se da je ovaj efekt važan za besmrtnost i transformaciju stanica, te omogućuje rezistentnost tumorskih stanica na oksidativni stres i adaptaciju stanica na uvjete hipoksije. Od vremena kada je otkriven ovaj fenomen, odvijala su se mnoga istraživanja koja su pomogla dubljem shvaćanju ovoga procesa. Bolje shvaćanje procesa iznjedrilo je mogućnosti dijagnoze i terapije, no još uvijek Warburgov efekt ne poznajemo dovoljno dobro. Ovaj rad predstavlja pregled činjenica i perspektive Warburg-ovog efekta u 21. stoljeću.One of the first studies on the energy metabolism of tumors was carried out in 1922, in the laboratory of Otto Warburg. He established that cancer cells exhibited a specific metabolic pattern, characterized by a shift from respiration to fermentation, which has been later named the Warburg effect, and that this is the main cause why normal cells become tumor cells. Here cells maintain a high glycolytic rate even in conditions of adequate oxygen supply, and accumulate large amounts of lactate. This seems to be important in immortalization and transformation of cell as it renders cells resistant to oxidative stress and adaptive to hypoxic condition. Considerable work has been done since Warburg first discovered this phenomenon, deepening our understanding of the process, with consequences for diagnosis and therapy, but still Warburg effect is not yet completely understood. This review presents facts and perspectives on the Warburg effect for the 21st century

Enhancement of betanin yield in transformed cells of sugar beet (Beta vulgaris L.)

Betanin belongs to a large family of betacyanin pigments, betalains, and in the food industry it is established as a powerful antioxidant and natural colorant. The main source of betanin is a red beet (Beta vulgaris L.), the yield depending on abiotic and biotic factors in the field. Sugar beet cells, transformed by a wild strain B6S3 of Agrobacterium tumefaciens, strongly produce betanin and could be a stable production source.With the aim of enhancing the yield, cell suspensions were initiated from friable calli. Biomass accumulation, betanin content and yield were monitored over 21 days in relation to changes of sucrose concentration, modifications of minerals in nutrient medium, and the usage of elicitors. Results showed that elevating sucrose levels from 3%to 4%, 5%, or 6%(w/v) in the original medium strongly induced biomass accumulation followed by an increase in betanin yield of up to 250%. Modification of minerals in the medium additionally increased betanin yield up to 20% in a few instances: 40 mg L–1 was recorded at day 10 with 5% and 6% of sucrose. The highest yield at 53 mg L–1 was reached at day 21 on 4% Suc, again with the modified medium. High sucrose concentrations positively affected betanin accumulation only during lag phase of the cell suspension, but afterwards the trend reversed. Calcium and yeast extract were used as abiotic and biotic elicitor, respectively, in the early exponential phase of subculture (day 7). Calcium ions (at 10 fold higher concentration than in the control) failed to increase betanin yield as well as yeast extract at 0.25% (w/v). Yeast extract at 1.25% provoked excretion of betanin at day 4, and cell necrosis at day 7 after elicitation. Taken together, in our system, sucrose affected betanin yield more strongly than medium modifications or elicitors. Yeast extract could be used for reverse- sequestration of betanin where the cells can be used over an extended period

Warburg effect: cancer cells metabolism

Prva istraživanja energetskog metabolizma tumora provodila su se 1922. godine u laboratoriju Otto Warburga. Warburg je ustanovio specifičan metabolizam stanica raka čija je karakteristika prijelaz s respiracije na fermentaciju - nazvan je Warburg-ov efekt. Wrburgov efekt predstavlja glavni razlog transformacije normalnih stanica u tumorske stanice. Tumorske stanice održavaju visoku razinu glikolize, čak i u uvjetima kada je doprema kisika stanicama dostatna, te akumuliraju velike količine laktata. Smatra se da je ovaj efekt važan za besmrtnost i transformaciju stanica, te omogućuje rezistentnost tumorskih stanica na oksidativni stres i adaptaciju stanica na uvjete hipoksije. Od vremena kada je otkriven ovaj fenomen, odvijala su se mnoga istraživanja koja su pomogla dubljem shvaćanju ovoga procesa. Bolje shvaćanje procesa iznjedrilo je mogućnosti dijagnoze i terapije, no još uvijek Warburgov efekt ne poznajemo dovoljno dobro. Ovaj rad predstavlja pregled činjenica i perspektive Warburg-ovog efekta u 21. stoljeću.One of the first studies on the energy metabolism of tumors was carried out in 1922, in the laboratory of Otto Warburg. He established that cancer cells exhibited a specific metabolic pattern, characterized by a shift from respiration to fermentation, which has been later named the Warburg effect, and that this is the main cause why normal cells become tumor cells. Here cells maintain a high glycolytic rate even in conditions of adequate oxygen supply, and accumulate large amounts of lactate. This seems to be important in immortalization and transformation of cell as it renders cells resistant to oxidative stress and adaptive to hypoxic condition. Considerable work has been done since Warburg first discovered this phenomenon, deepening our understanding of the process, with consequences for diagnosis and therapy, but still Warburg effect is not yet completely understood. This review presents facts and perspectives on the Warburg effect for the 21st century

Warburg effect: cancer cells metabolism

Prva istraživanja energetskog metabolizma tumora provodila su se 1922. godine u laboratoriju Otto Warburga. Warburg je ustanovio specifičan metabolizam stanica raka čija je karakteristika prijelaz s respiracije na fermentaciju - nazvan je Warburg-ov efekt. Wrburgov efekt predstavlja glavni razlog transformacije normalnih stanica u tumorske stanice. Tumorske stanice održavaju visoku razinu glikolize, čak i u uvjetima kada je doprema kisika stanicama dostatna, te akumuliraju velike količine laktata. Smatra se da je ovaj efekt važan za besmrtnost i transformaciju stanica, te omogućuje rezistentnost tumorskih stanica na oksidativni stres i adaptaciju stanica na uvjete hipoksije. Od vremena kada je otkriven ovaj fenomen, odvijala su se mnoga istraživanja koja su pomogla dubljem shvaćanju ovoga procesa. Bolje shvaćanje procesa iznjedrilo je mogućnosti dijagnoze i terapije, no još uvijek Warburgov efekt ne poznajemo dovoljno dobro. Ovaj rad predstavlja pregled činjenica i perspektive Warburg-ovog efekta u 21. stoljeću.One of the first studies on the energy metabolism of tumors was carried out in 1922, in the laboratory of Otto Warburg. He established that cancer cells exhibited a specific metabolic pattern, characterized by a shift from respiration to fermentation, which has been later named the Warburg effect, and that this is the main cause why normal cells become tumor cells. Here cells maintain a high glycolytic rate even in conditions of adequate oxygen supply, and accumulate large amounts of lactate. This seems to be important in immortalization and transformation of cell as it renders cells resistant to oxidative stress and adaptive to hypoxic condition. Considerable work has been done since Warburg first discovered this phenomenon, deepening our understanding of the process, with consequences for diagnosis and therapy, but still Warburg effect is not yet completely understood. This review presents facts and perspectives on the Warburg effect for the 21st century

Evaluation of Protein Extraction Methods for Proteomic Analysis of Non-Model Recalcitrant Plant Tissues

Plant tissues contain relatively low amounts of proteins whose extraction is often difficult due to the presence of interfering compounds such as rigid cellulosic cell wall, storage polysaccharides, lipids and other contaminants that can cause protein degradation or modification. Therefore it is important to optimize protein extraction and to establish a robust protocol for two-dimensional gel electrophoresis (2-DE) and downstream processing. In this study, acetone, trichloroacetic acid/acetone and Tris-buffered phenol/methanol extraction protocols were evaluated on non-model and recalcitrant plants: a Beta vulgaris L. in vitro cell line, Mammillaria gracilis Pfeiff. in vitro plants and Sempervivum tectorum L. leaves. Although phenol extraction was more time-consuming than the other two methods, it gave almost two-fold higher protein yield, and spectral analysis showed less contamination. SDS-PAGE, 2-DE and bioinformatic analysis showed that protein extraction using phenol was superior to the other two methods, providing more protein bands or spots on the gels and less proteolysis. These results lead to the conclusion that the phenol method is the most suitable protein extraction method for these non-model and recalcitrant plant tissues. (doi: 10.5562/cca1804

Anti-cancer effect of two novel palladium (II) complexes on human leukemia cell lines

Razvoj djelotvornih lijekova protiv leukemija kod ljudi je još uvijek u tijeku, no dosada nije pronađena potpuno zadovoljavajuća terapija. Nedavno je objavljeno da paladijevi kompleksi imaju značajnu protutumorsku aktivnost, kao i nižu citotoksičnost u usporedbi s već postojećim kemoterapeuticima u praksi. Protutumorsko djelovanje dva novootkrivena paladijeva kompleksa, [Pd(sac)(terpy)](sac)·4H2O i [PdCl(terpy)](sac)·2H2O, je ispitano na tri leukemijske stanične linije: Jurkat, MOLT-4 i THP-1 u usporedbi s cisplatinom i adriamicinom. Citotoksični učinak lijekova je određen MTT testom. Apoptoza je određena protočnom citometrijom bojanjem stanica FITC- Aneksinom V i propidij jodidom, te određivanjem aktivnosti kaspaze 3. Nadalje, istraživanjem molekule PARP-a utvrđeno je dolazi li do apoptoze ili nekroze. Oba kompleksa ponajviše potiču apoptozu, no uočena je i nekroza. Rezultati in vitro istraživanja pokazali su da paladijevi (II) spojevi imaju potencijalni protutumorski učinak u liječenju leukemija kod ljudi, no potrebne su daljnje analize kako bi se utvrdio mehanizam djelovanja, te djelovanje u in vivo sustavu.Razvoj djelotvornih lijekova protiv leukemija kod ljudi je još uvijek u tijeku, no dosada nije pronađena potpuno zadovoljavajuća terapija. Nedavno je objavljeno da paladijevi kompleksi imaju značajnu protutumorsku aktivnost, kao i nižu citotoksičnost u usporedbi s već postojećim kemoterapeuticima u praksi. Protutumorsko djelovanje dva novootkrivena paladijeva kompleksa, [Pd(sac)(terpy)](sac)·4H2O i [PdCl(terpy)](sac)·2H2O, je ispitano na tri leukemijske stanične linije: Jurkat, MOLT-4 i THP-1 u usporedbi s cisplatinom i adriamicinom. Citotoksični učinak lijekova je određen MTT testom. Apoptoza je određena protočnom citometrijom bojanjem stanica FITC- Aneksinom V i propidij jodidom, te određivanjem aktivnosti kaspaze 3. Nadalje, istraživanjem molekule PARP-a utvrđeno je dolazi li do apoptoze ili nekroze. Oba kompleksa ponajviše potiču apoptozu, no uočena je i nekroza. Rezultati in vitro istraživanja pokazali su da paladijevi (II) spojevi imaju potencijalni protutumorski učinak u liječenju leukemija kod ljudi, no potrebne su daljnje analize kako bi se utvrdio mehanizam djelovanja, te djelovanje u in vivo sustavu