“Tobacco Killing Cancer”: Say it Ain’t So
There’s a new research finding making the rounds on sensationalised mass media with breathless headlines about how a molecule from the tobacco plant can ‘explode’ and kill cancer cells. The work is actually very interesting, but as usual the #ScienceMediaHype is not warranted. So what is it all about?
✤ Scientists were looking at a molecule isolated from the flowers of the ornamental tobacco plant Nicotiana alata. This molecule, named NaD1 derives its name from Nicotiana alata defensin 1. NaD1 is part of a group of molecules known as defensins, which are really interesting in their own right.
✤ What are defensins? They are small protein molecules found across many different species of animals and plants. As their name implies, these molecules function as part of the host innate immune system; they have anti-microbial activity against bacteria, viruses and fungi. As a general rule, defensins bind to the cell membrane of the microbe causing changes to cell membrane structure, allowing essential ions and nutrients to leak out, thereby killing the cell. However, the exact mechanism by which defensins bind to the cell membrane has been unclear up until now.
✤ In this study, scientists identified that the defensin NaD1 binds to a small phospholipid (a lipid molecule with a phosphate molecule attached to it) known as PIP2. This binding results in a NaD1:PIP2 complex which they visualised using transmission electron microscopy. NaD1 is able to polymerise and form long string-like structures in the presence of PIP2. This binding is crucial for NaD1’s microbe-killing abilities.
✤ Next, the scientists tested the ability of NaD1 to cause changes in the cell membrane. They used a dye that normally does not cross the cell membrane to monitor cell membrane integrity; if the dye shows up inside the cells, the cell membrane is obviously damaged. Sure enough, NaD1 caused an influx of the dye into the cell, and also leakage of ATP molecules from the cell to the outside. Using scanning laser confocal microscopy, the scientists then visualised the effect of NaD1 on HeLa (cervical cancer) cells. The membrane blebbing (protrusions) and intake of the red dye can be seen in the gif.
✤ Since PIP2 is found in many different cell types, the scientists also evaluated NaD1’s cell membrane destroying capabilities in many different cell types. They found that immortal cells (i.e. tumor cells) were more susceptible to killing by NaD1 than normal cells. This is attributed to the different properties that cancer cell membranes have when compared against normal cell membranes, and the precise mechanism for this is yet to be discovered.
✤ Defensins are really interesting molecules with a whole range of functions. In this study, scientists identified the precise mechanism by which NaD1 destabilises the cell membrane by specifically binding to PIP2. They are capable of forming oligomers to carry out diverse functions within the immune system, and this study explains in detail one such mechanism. This is fascinating in its own right, and does not need to be labelled with a ridiculous ‘tobacco plant can cure cancer’ label to make it newsworthy!