New molecules may help fight multi-drug resistant cancers

Australian researchers have discovered a new class of molecules originally derived from sea snails that are showing promising results against multi-drug resistant cancers.
The discovery was made by scientists atUniversity of Wollongong (UOW) and Illawarra Health and Medical Research Institute (IHMRI).
The molecules calledN-alkylisatins killed 100 per cent of drug resistant cancer cells in just 48 hours, compared with a chemotherapy drug commonly used to treat breast cancer which killed only 10 per cent of cells in the same time period.
The finding was published in the journalHeliyon.
"The findings were actually quite surprising given that our molecules share similar properties to some of the chemo-therapeutics that are currently used and are ineffective," Perrow said.

"Because of this similarity, we weren't expecting that they would have such an effect on cell lines that are normally resistant to these types of molecules," she said.

Multidrug resistance, whereby cancers develop resistance to chemotherapy drugs and are no longer responsive to treatment is a major limitation to the current management of the disease.
It affects patients with a variety of blood cancers and solid tumours, including breast, ovarian, pancreatic, and lower gastrointestinal tract cancers.
"These results are exciting because any new molecule that we discover has an effect on multi-drug resistant cells has major implications for improving survival in these patients and ultimately reducing relapse," Perrow said.

The chemicals were originally isolated and the anticancer properties determined in 2002, in collaboration with Southern Cross University's Kirsten Benkendorff, from the egg masses of the White Rock sea snail (Dicathasis orbita).
These are commonly found on rocky shores around Australia and New Zealand.
Interestingly, venom from the Queensland cone sea snail has also proved promising for new pain treatments.
To create the newN-alkylisatin molecules, Perrow worked with colleagues in the School of Chemistry to tweak the chemical composition of the original egg formula, eventually boosting its cancer-killing properties by 1000 times.
The team then took lab-grown cancer cells that were either sensitive or resistant to commercial chemotherapies and exposed them to different concentrations ofN-alkylisatins for up to 48 hours.

"We screened these compounds against a panel of different cancer cell lines that we grow in the lab and we found that they had activity against all of them,"Perrow said.
Perrow and her team are now working to optimise the drugs so that they are safe for use. This involves packaging theN-alkylisatins into small lipid-based nanoparticles so they become non-toxic and safe for injection.
"We are now looking at how these molecules could be used to fight breast cancer," Perrow said.