By Admin at 23 Aug 2016, 01:11 AM
A new chemotherapy drug has shown promise for treating both childhood and adult cancers with improvements above-and-beyond typical chemotherapy treatment. The treatment involves a novel class of antitumor amphiphilic amines (RCn).
The lead compound, RC16, was tested by researchers from the University of Bologna and Nationwide Children's Hospital in Columbus, Ohio and found to have anti-cancer activity against multiple cancer cell lines, including sarcomas, lymphoma and neuroblastoma.
Part of what makes this chemotherapy treatment so promising is that RCn, and particularly RC16, is more toxic to cancer cells than healthy cells, by a measure of 10-fold. This means that a low dose of the drug could effectively kill cancer cells while only minimally affecting normal cells.
The tests showed RC16 worked to shrink human tumors that were implanted into mice. It was also effective against neuroblastoma in mice, both when administered orally and intravenously.
RC16 also has a unique amphiphilic molecular structure, which means it has both polar, water-soluble regions and nonpolar, water-insoluble regions. When put in water, amphiphilic molecules form aggregates called micelles, and, indeed, the researchers found “the amphiphilic character of RC16 triggered a spontaneous molecular self-assembling in water with formation of micelles …”
This is important because micelles are often used for their ability to dissolve and carry drugs that may not otherwise be soluble in water. In other words, they may enhance the drug’s effectiveness or make them more bioavailable.
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This was the case with RC16, which researchers noted allowed “complexation of [the cancer drugs] Doxorubicin, Etoposide and Paclitaxel.” In addition, the micelles significantly increased the anti-tumor activity of these drugs by enhancing their solubility in water, which improved their biologic availability.
RC16 was successfully tested not only for its anti-cancer activities alone but also for its ability to be complexed with other chemotherapy agents to enhance their effectiveness. Isabella Orienti, Ph. D, professor of pharmacy and biotechnology at the University of Bologna, said:
“The antitumor activity of lipophilic amines was interesting because of its action on the mitochondria and lysosomes of cells. Moreover, their amphiphilic character improves their bioavailability …
We correctly hypothesized these amphiphilic amines would have high antitumor activity and high bioavailability."
The novel treatment will require further testing before it will potentially be available, but it represents a new type of treatment that may target cancer via multiple mechanisms, including being directly harmful to cancer cells and serving as drug-delivery vehicles. The researchers wrote in Pharmaceutical Research:
“In summary, we have developed a novel, multimechanistic antitumor drug class that shows promise for cancer therapy.
These amphiphilic amines bind to and induce anticancer activity by several mechanisms of action with differential effects on normal cells, resulting in a clinically significant therapeutic window.
Furthermore, these agents are useful for encapsulating traditional chemotherapies and thereby enhancing their efficacy and reducing their side-effects.”
Sources:
Pharmaceutical Research July 25, 2016
Medical Xpress July 27, 2016
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