A study has detailed new findings that researchers say confirm the anticancer properties of a newly discovered agent called FL118. The investigators say their findings are "promising" and open doors for further research into the compound.
Their results were published in the journal Molecular Pharmaceutics.
The research team, led by Dr. Fengzhi Li of Roswell Park Cancer Institute in Buffalo, first identified FL118 as a potential anticancer agent in 2012. They discovered that the compound had encouraging toxicity profiles and worked in a unique way to inhibit multiple cancer survival.
According to the investigators, FL118 is similar in structure to camptothecin - a component found in the stem and bark of a tree called Camptotheca acuminata that is native to China.
Camptothecin has long been used as a traditional Chinese remedy for the treatment of cancer. Two agents that have been synthesized from the component - irinotecan and topotecan - are currently used to treat solid-tumor cancers.
But the researchers note that these agents severely damage healthy cells as well as cancerous cells, and many of them have proven ineffective as anticancer agents.
FL118 'effective against cancer-survival proteins'
In this most recent study, the team analyzed the lactone ring of FL118 and the structure-activity relationship (SAR) of the hydroxyl group within it.
The researchers assessed the effectiveness of FL118 in curbing cancer-survival proteins in vivo and in vitro, as well as seven new compounds derived from FL118 and FL113 - a sister molecule.
From this, the team found that FL118 was consistently more effective in inhibiting cancer-survival proteins, compared with FL113 - both in vivo and in vitro.
Furthermore, through analyzing the seven compounds derived from FL118, the researchers found that high antitumor effectiveness is reliant on the availability of a hydroxyl group within the compound.
"We learned that the steric configuration of FL118, the way the atoms are arranged within the molecule, is critically important to its effectiveness as an anticancer agent," explains Dr. Li.
"Specifically, we now know that a free hydroxyl group is a key component for any FL118 analogs we develop, and we'll apply that finding as we move forward with subsequent studies."
Dr. Li adds that their findings suggest FL118 "will be an outstanding model on which to base new analogs that will represent even more promising investigational therapies for personalized cancer treatment."
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