Cancer and chemotherapy: there are perhaps no two words more unnerving in all the medical lexicon. Almost everyone has been touched by cancer in some way and many have witnessed the ravages chemotherapy visits upon those who undergo it.
Part of the reason chemotherapy is so damaging is that it cannot target cancer cells exclusively. The chemicals that make up chemotherapeutic cocktails typically attack cells that divide rapidly, including healthy cells in the bone marrow, digestive tract and hair follicles. Next generation chemotherapy drugs have narrower mechanisms of action that endeavor to avoid damaging non-cancer cells. A research team at Australia’s La Trobe University has recently identified one such molecule and they claim it is capable of selectively targeting and killing cancer cells.
In an ironic twist, the molecule is produced by a species of ornamental tobacco.
The Australian group published their results in the online journal eLife on April 1st. In their study, they examined NaD1, which is a type of “cationic antimicrobial peptide,” more commonly called a “definsin.”
According to an article entitled “Plant Definsins” available on the National Center for Biotechnology Information (NCBI) website, “defensins are diverse members of a large family of [positively charged] host defense peptides (HDP), widely distributed throughout the plant and animal kingdoms.”
There are a wide variety of definsins, both across species and within the genomes of single plants. According to the NCBI article, “the Arabidopsis genome alone contains more than 300 defensin-like (DEFL) peptides.”
In their normal role within plant tissues, “most plant defensins are involved in defense against a broad range of fungi,” according to the NCBI piece.
The research team at La Trobe wanted to know more about how NaD1 targeted invading organisms and how the molecule was subsequently able to destroy them. They suspected certain components on the invader cell’s membranes would attract the definsin, which would then bind to the cells and kill them.
According to the paper published in eLife, the researchers were successful in identifying a membrane lipid called PIP2 as the target of NaD1. This same lipid is found in the cell membranes of mammalian cells, which led the research team to try exposing various human cells to NaD1.
What they found was unexpected… and astounding.
Researcher Dr. Mark Hulett, quoted in a La Trobe University press release, said “we’ve found NaD1 can target cancerous cells and has little or no effect on those that are healthy.”
The release said, “The defense molecule, called NaD1, works by forming a pincer-like structure that grips onto lipids present in the membrane of cancer cells and rips it open, causing the cell to expel its contents and explode.”
In the conclusion of their eLife publication, the La Trobe team speculated why cancers cells are more sensitive to NaD1 than their healthy counterparts.
“The increased sensitivity of tumor cells to NaD1 compared with its effects on healthy primary cells may be attributed to a number of differences in the physical properties of the plasma membranes of these two cell types […],” the team wrote, “which could allow stronger initial electrostatic interactions between the [positively charged] NaD1 and the cell surface.”
“The precise mechanism of action for the increased sensitivity of mammalian tumor cells over normal cells to defensins and whether this approach can be harnessed for selective tumor cell killing remains to be determined,” it concluded.
There is a plentitude of research to be done before the true efficacy of NaD1 as a selective cancer-killer can be brought to light. There is a huge difference between demonstrating something works in the lab versus getting it to behave similarly within a human body, but Hulett and his team are optimistic. If they are successful, their discovery could usher in a new class of cancer drugs that is not only effective, but also far more gentile than chemotherapy and radiation.
