Lotta contro i tumori: individuate nuove molecole che attivano il sistema immunitario / Fight against tumors: identify new molecules that activate the immune system
Lotta contro i tumori: individuate nuove molecole che attivano il sistema immunitario / Fight against tumors: identify new molecules that activate the immune system
Segnalato dal Dott. Giuseppe Cotellessa / Reported by Dr. Giuseppe Cotellessa
Interagendo con strutture non canoniche del DNA note come “quartetti di guanine” (G4), alcuni composti chimici provocano la morte delle cellule tumorali e allo stesso tempo stimolano i meccanismi di difesa dell’organismo.
Un gruppo di ricerca dell’Università di Bologna ha individuato per la prima volta alcuni composti chimici in grado di provocare un particolare tipo di instabilità genomica all’interno del DNA delle cellule tumorali: un effetto che può portare alla morte delle cellule stesse, stimolando nel contempo la risposta del sistema immunitario contro la malattia.
Al centro dello studio c’è il ruolo chiave di strutture non canoniche del DNA note come “quartetti di guanine” (G4): una tipologia di danno genetico che è in grado di attivare i meccanismi di difesa dell’organismo. I risultati dello studio – pubblicati sulla rivista PNAS – aprono la strada a nuove modalità di trattamento dei tumori.
CELLULE INSTABILI
Al centro dello studio c’è il ruolo chiave di strutture non canoniche del DNA note come “quartetti di guanine” (G4): una tipologia di danno genetico che è in grado di attivare i meccanismi di difesa dell’organismo. I risultati dello studio – pubblicati sulla rivista PNAS – aprono la strada a nuove modalità di trattamento dei tumori.
CELLULE INSTABILI
La molecola di DNA custodita all'interno di ogni cellula umana è composta da circa 6,5 miliardi di "mattoncini" chiamati nucleotidi, che possono essere di quattro tipi a seconda delle quattro diverse basi azotate presenti: adenina (A), timina (T), guanina (G) e citosina (C). Questa architettura estremamente complessa è però anche particolarmente esposta ad agenti esterni ed interni (radiazioni, tossine, agenti chimici, ma anche sottoprodotti del normale metabolismo cellulare) che finiscono per danneggiare i nucleotidi: ogni danno provoca un’alterazione nel genoma che può portare a mutazioni o riarrangiamenti dei cromosomi, minacciando così il corretto funzionamento della cellula.
Le cellule tumorali sfruttano comunemente queste alterazioni per adattarsi a condizioni diverse ed evitare gli effetti delle terapie. Ma se da un lato l’instabilità genomica favorisce la malattia, in alcune occasioni può anche rivelarsi un’arma a doppio taglio. “In alcuni casi, il danno al DNA può diventare un campanello d'allarme che risveglia i meccanismi di difesa dell’organismo”, spiega Giovanni Capranico, docente dell’Università di Bologna che ha coordinato lo studio. “La nostra ricerca mostra infatti come alcuni composti che interagiscono con strutture non canoniche del DNA note come quartetti di guanine (G4) possono portare ad una particolare instabilità genomica in grado probabilmente di attivare la risposta immunitaria”.
QUARTETTI DI GUANINE
Osservati per la prima volta solo pochi anni fa, i quartetti di guanine (G4) sono strutture di DNA che invece della classica doppia elica presentano una quadrupla elica formata dall’incontro di quattro sequenze ricche di guanina. Si tratta di “formazioni instabili” e per questo possono rivelarsi un punto strategico per attivare meccanismi in grado di provocare la morte delle cellule tumorali. Non a caso molti scienziati sono impegnati da tempo nella ricerca di composti chimici capaci di interagire attivamente con i G4 e di essere efficaci nella terapia dei tumori.
“Lo studio è partito dall’analisi del meccanismo molecolare di alcuni composti che interagiscono con i quartetti di guanine, uno dei quali è stato sintetizzato proprio all’Università di Bologna, nei laboratori del nostro Dipartimento di Farmacia e Biotecnologie dalla dottoressa Rita Morigi”, spiega il professor Capranico. L’azione di questi composti è particolarmente rilevante perché agisce allo stesso tempo su due fronti: da un lato provoca la morte delle cellule tumorali e dall’altro attiva i meccanismi di difesa dell’organismo stimolando la risposta immunitaria contro la malattia. “Queste molecole – conferma Capranico – sono in grado di stabilizzare i G4 e anche altre strutture non canoniche del DNA all’interno delle cellule tumorali: un fenomeno che provoca gravi disfunzioni nell’attività del genoma”. Un risultato che apre la strada a nuove modalità di trattamento dei tumori. “Il risultato è positivo, ma la ricerca deve continuare perché non abbiamo ancora la molecola giusta, adeguata per il trattamento di pazienti oncologici”, precisa il prof. Capranico.
ENGLISH
Interacting with non-canonical DNA structures known as "quartets of guanine" (G4), some chemical compounds cause the death of cancer cells and at the same time stimulate the body's defense mechanisms.
A research group of the University of Bologna has identified for the first time some chemical compounds able to provoke a particular type of genomic instability within the DNA of the tumor cells: an effect that can lead to the death of the cells themselves, stimulating in the at the same time the response of the immune system against the disease.
At the center of the study is the key role of non-canonical DNA structures known as "guanine quartets" (G4): a type of genetic damage that is able to activate the body's defense mechanisms. The results of the study - published in the journal PNAS - open the way to new ways of treating cancer.
INSTABLE CELLS
The DNA molecule stored inside each human cell is made up of about 6.5 billion "bricks" called nucleotides, which can be of four types depending on the four different nitrogenous bases present: adenine (A), thymine (T ), guanine (G) and cytosine (C). This extremely complex architecture, however, is also particularly exposed to external and internal agents (radiation, toxins, chemical agents, but also by-products of normal cellular metabolism) that end up damaging the nucleotides: each damage causes an alteration in the genome that can lead to mutations or rearrangements of the chromosomes, thus threatening the proper functioning of the cell.
Cancer cells commonly exploit these alterations to adapt to different conditions and avoid the effects of the therapies. But while genomic instability favors the disease, on some occasions it can also turn out to be a double-edged sword. "In some cases, DNA damage can become a wake-up call that awakens the body's defense mechanisms," explains Giovanni Capranico, a professor at the University of Bologna who coordinated the study. "Our research shows that some compounds that interact with non-canonical DNA structures known as guanine quartets (G4) can lead to a particular genomic instability likely to activate the immune response".
GUARANTEED QUARTETS
Observed for the first time only a few years ago, the quanets of guanine (G4) are structures of DNA that instead of the classical double helix present a quadruple helix formed by the meeting of four sequences rich in guanine. These are "unstable formations" and for this reason they can be a strategic point to activate mechanisms able to cause the death of cancer cells. It is no coincidence that many scientists have long been engaged in the research of chemical compounds capable of actively interacting with G4 and being effective in the treatment of tumors.
"The study started from the analysis of the molecular mechanism of some compounds that interact with the guanine quartets, one of which was synthesized at the University of Bologna, in the laboratories of our Department of Pharmacy and Biotechnology by Dr. Rita Morigi", explains Professor Capranico. The action of these compounds is particularly relevant because it acts at the same time on two fronts: on the one hand it causes the death of the cancer cells and on the other activates the body's defense mechanisms by stimulating the immune response against the disease. "These molecules - confirms Capranico - are able to stabilize the G4 and also other non-canonical DNA structures within the tumor cells: a phenomenon that causes serious dysfunctions in the activity of the genome". A result that opens the way for new ways of treating cancer. "The result is positive, but the research must continue because we do not yet have the right molecule, adequate for the treatment of cancer patients", states prof. Capranico.
Interacting with non-canonical DNA structures known as "quartets of guanine" (G4), some chemical compounds cause the death of cancer cells and at the same time stimulate the body's defense mechanisms.
A research group of the University of Bologna has identified for the first time some chemical compounds able to provoke a particular type of genomic instability within the DNA of the tumor cells: an effect that can lead to the death of the cells themselves, stimulating in the at the same time the response of the immune system against the disease.
At the center of the study is the key role of non-canonical DNA structures known as "guanine quartets" (G4): a type of genetic damage that is able to activate the body's defense mechanisms. The results of the study - published in the journal PNAS - open the way to new ways of treating cancer.
INSTABLE CELLS
The DNA molecule stored inside each human cell is made up of about 6.5 billion "bricks" called nucleotides, which can be of four types depending on the four different nitrogenous bases present: adenine (A), thymine (T ), guanine (G) and cytosine (C). This extremely complex architecture, however, is also particularly exposed to external and internal agents (radiation, toxins, chemical agents, but also by-products of normal cellular metabolism) that end up damaging the nucleotides: each damage causes an alteration in the genome that can lead to mutations or rearrangements of the chromosomes, thus threatening the proper functioning of the cell.
Cancer cells commonly exploit these alterations to adapt to different conditions and avoid the effects of the therapies. But while genomic instability favors the disease, on some occasions it can also turn out to be a double-edged sword. "In some cases, DNA damage can become a wake-up call that awakens the body's defense mechanisms," explains Giovanni Capranico, a professor at the University of Bologna who coordinated the study. "Our research shows that some compounds that interact with non-canonical DNA structures known as guanine quartets (G4) can lead to a particular genomic instability likely to activate the immune response".
GUARANTEED QUARTETS
Observed for the first time only a few years ago, the quanets of guanine (G4) are structures of DNA that instead of the classical double helix present a quadruple helix formed by the meeting of four sequences rich in guanine. These are "unstable formations" and for this reason they can be a strategic point to activate mechanisms able to cause the death of cancer cells. It is no coincidence that many scientists have long been engaged in the research of chemical compounds capable of actively interacting with G4 and being effective in the treatment of tumors.
"The study started from the analysis of the molecular mechanism of some compounds that interact with the guanine quartets, one of which was synthesized at the University of Bologna, in the laboratories of our Department of Pharmacy and Biotechnology by Dr. Rita Morigi", explains Professor Capranico. The action of these compounds is particularly relevant because it acts at the same time on two fronts: on the one hand it causes the death of the cancer cells and on the other activates the body's defense mechanisms by stimulating the immune response against the disease. "These molecules - confirms Capranico - are able to stabilize the G4 and also other non-canonical DNA structures within the tumor cells: a phenomenon that causes serious dysfunctions in the activity of the genome". A result that opens the way for new ways of treating cancer. "The result is positive, but the research must continue because we do not yet have the right molecule, adequate for the treatment of cancer patients", states prof. Capranico.
Da:
http://www.lescienze.it/lanci/2019/01/21/news/lotta_contro_i_tumori_individuate_nuove_molecole_che_attivano_il_sistema_immunitario-4264343/?ref=nl-Le-Scienze_25-01-2019
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