anti-cancer drug

An anticancer drug opens a new path for the treatment of Parkinson’s

Posted by

0


Once they enter the body, drugs, apart from carrying out their therapeutic function, are biochemically transformed by the action of the metabolic machinery, a process that facilitates their expulsion. This biotransformation results in a gradual disappearance of the drug, which is converted into its metabolites.

These, in turn, can reach high concentrations in the body and also show a biological activity that may be different from that of the original drug. That is, the metabolites and the drug coexist in the body and can cause effects different from those obtained with the individual molecules.

This is the case of Rucaparib, a drug used in chemotherapy for ovarian cancer, breast cancer, and, more recently, prostate cancer, and its metabolite, the M324 molecule. Rucaparib is part of a group of drugs designed to treat several types of cancers that show alterations in DNA repair. Specifically, they are inhibitors of the PARP1 enzyme, involved precisely in the process of repairing mutations in the genetic material.

A study led by researchers Albert A. Antolin, from the Oncobell program of the Bellvitge Biomedical Research Institute (IDIBELL) and ProCure of the Catalan Institute of Oncology (ICO), and Amadeu Llebaria, from the Institute of Advanced Chemistry of Catalonia (IQAC-CSIC ), has shown that Rucaparib and its main metabolite M324 exhibit differential activities.

Published in the journal Cell Chemical Biology, the paper has analyzed Rucaparib and M324, making a computational prediction of the metabolite’s activity. The article describes the synthesis of M324 and its biological assay, demonstrating that the drug and its metabolite have differentiated activities and act synergistically in some prostate cancer cell lines.

Surprisingly, M324 reduces the accumulation of the protein α-synuclein (an important component of Lewy bodies) in neurons derived from patients with Parkinson’s, a neurodegenerative disease characterized by a movement disorder, and in which neurons do not produce sufficient amounts of the neurotransmitter dopamine.

Specifically, the synergy demonstrated between Rucaparib and M324 in prostate cancer cell lines could have an impact on clinical trials for advanced stages of this type of cancer. On the other hand, the fact that M324 is capable of reducing the abnormal accumulation of α-synuclein in neurons derived from stem cells of a Parkinson’s patient highlights the therapeutic potential of this metabolite and its possible pharmacological application for the treatment of this neurodegenerative disease.

These results have been obtained thanks to the collaboration of the IDIBELL and ICO groups led by Miquel Àngel Pujana and Álvaro Aytés, and the group of Antonella Consiglio, from IDIBELL and the UB.

Researchers have used computational and experimental methods to characterize comprehensively, and for the first time, the pharmacology of the M324 molecule. The first author of the work, Huabin Hu, has made an exhaustive prediction of the differential activity of the original drug and its product, which translates into different spectra of the phosphorylation pattern of cellular proteins.

Carme Serra, from the MCS group at IQAC-CSIC, has synthesized the metabolite M324, which has allowed experimental verification of the computational prediction in biological and cellular assays. The results obtained could have implications for clinical treatment with Rucaparib and, in turn, open new opportunities for drug discovery.

In summary, the study points towards a new conceptual perspective in pharmacology: one that considers drug metabolism not as an undesirable process that degrades and eliminates the therapeutic molecule from the body but rather as one that can have potential advantages from a therapeutic point of view. Indeed, the work highlights the importance of characterizing the activity of drug metabolites to comprehensively understand their clinical response and apply it in precision medicine.

Using Hot Sauce Is a Really Easy Way to Improve Your Diet, Say Experts

Posted by

0


If you’re the type of person who breaks out the hot sauce at the start of every single meal, congratulations – you’re really onto something there.

A slew of studies over the past few years have been piecing together evidence that capsaicin – an active component of chili peppers – promotes a higher turnover of cells in the body, which could explain why eating spicy foods has been linked to a reduced risk of mortality and slowed cancer development.

 

“The bottom line is that any kind of vegetable material you consume will improve your health,” nutrition expert David Popovich from Massey University in New Zealand toldTIME magazine back in 2015.

“But hot peppers are really beneficial for you, if you can take the spice.”

Popovich has been investigating the mechanism by which capsaicin appears to slow the growth of cancer cells in the lab.

Back in 2006, researchers discovered that high doses of capsaicin could slow the growth of prostate cancer cells in mice by up to 80 percent, while leaving the healthy cells alone, and in 2015, a separate team demonstrated for the first time how this spicy compound binds to cancer cells and triggers changes in their internal structure.

It’s not yet known exactly how capsaicin is interacting with cancer cells to slow their growth, but scientists have observed it binding to the outer membrane and lodging itself in, which appears to trigger chemical changes in the surface of the cell.

“If you add enough of it, it actually causes the membranes to come apart,” Fiona MacDonald reported for us at the time.

Popovich has observed the slowed growth of cancer cells in his own lab, and told Mandy Oaklander from TIME that the most popular hypothesis to explain what’s going on here is that the capsaicin is promoting a process known as apoptosis – programmed cell death that leads to a higher turnover of cells.

It’s basically regulated cell suicide in the interest of cleaning up cells that are no longer needed.

“That’s one of the ways scientists think capsaicin and other active compounds in vegetables can prevent cancer development: by stimulating apoptotic cell death,” says Popovich.

While some researchers are investigating the potential of incorporating a concentrated form of capsaicin into a new anti-cancer drug, José de Jesús Ornelas-Paz from the Research Centre for Food and Development in Mexico told Oaklander the real benefits appear to come from the whole chili pepper – not just that one active ingredient.

“Pungent peppers are a cocktail of bioactive compounds,” he said.

“Blending, cutting and cooking improve the release of [these compounds] from pepper tissue, increasing the amount available for absorption.”

Just as adding certain types of protein to a salad can actively improve your uptake of nutrients, research has shown that it’s not just what you eat, but how you eat it.

According to Ornelas-Paz, because capsaicin is a fat-soluable compound, you should definitely try pairing it with a bit of fat or oil to help your body absorb it (which isn’t exactly difficult, unless you only like eating raw vegetables with your hot sauce).

As with many things to do with our diet, scientists still have to figure out the exact mechanism by which capsaicin could be altering our cells, but there’s enough evidence out there to suggest that it’s doing something beneficial.

In another 2015 study, a team from Harvard University assessed the health of almost half a million Chinese adults, and found that those who ate spicy food six or seven times a week had a 14 percent lower mortality risk than those who seldom ate it.

So apply that spicy condiment with abandon until you’re blinded by the salty tears of too much hot sauce sweet, sweet vindication. You might look ridiculous, but at least you know you’ve got science on your side.