cisplatinskull.JPGDid you know martinis are nothing but liquor with a spritz of vermouth? There I was finishing my third Classy Martini, a vodka martini with shaved ice, a shot of Dewar’s scotch (I substitute with Laphroiag), and blue cheese stuffed olives, when SUDDENLY, I noticed a guy was talking to me. This was odd because that guy wasn’t talking to me mere femtoseconds before hand and now, there he was, wobbling uncontrollably along with the rest of the room trying to give me a cigar bullet. Shit. The prior 20 minutes were totally missing from my life and, worse yet; neither the room nor the man was wobbling at all. Needless to say, a few minutes latter $32 dollars worth of Classy Martinis came roaring out of my mouth – the sonic boom woke the dog – and I wanted to die. I can’t come up with any decent way to connect an introductory story with Cisplatin, the drug of the week, aside from both alcohol and Cisplatin are toxic and yet so wonderful we refuse to let them go. So, there you go. Cisplatin is your mom.

Cisplatin is an anti cancer drug of notable repute. Indeed, it scarcely requires an introduction, though a reasonable review is certainly in order. The structural simplicity of this anticancer drug is in stark contrast to other anticancer drugs such as taxol. Cisplatin has been off patent for years and sales are a bit difficult to track, though its modern day equivalent, Paraplatin rakes in nearly a billion a year and is off patent as well (suck it cisplatin.JPGBristol-Myers Squibb.) Both drugs had been in hot contention for a number of years as BMS attempted to extend the patent of cisplatin illegally by fraudulently filing a duplicate patent with the (apparent) blessing of Michigan State (which was earning millions of dollars per year from royalties.) The action kept cisplatin expensive and forced states and patients to pay significantly more than what they should have. This appalling action is simply one of many in BMS’s long history of fraud and controversy.

Anyway…

basepaired.gifIt’s pretty well known that Cisplatin binds to DNA and crinkles the hell out of. (To the left you see platinum is where it shouldn’t be.) This deformation of DNA makes the cell freak out, and when it cant put the shambles of its immortalized life back together it pulls out a gun and apoptosilize its brains all over the cell membrane. You can read all that crapola and delve into the x-ray structure in this free very technical article if you’re interested. Briefly: The clorine-platinum bonds are labile. Where chlorine concentrations are low, such as inside the cell, they will effectively be displaced by water generating the charged, unstable, PtCl(NH3)2H2O+. It is this compound that binds to the N7 atom of a purine (though, it can bind elsewhere). The second chloride becomes displaces and the next base it connects to, usually another purine, totally screws up the helix because, naturally, purines aren’t supposed to be a wopping 1 atom apart. This makes the pretty double helix kink and suck at life.

cisplatingunnafuckyouupsucka2.GIF

This mechanism affects faster dividing (cancer) cells more so than normal cells. This also gives rise to cisplatin’s horrible toxicity. Nevertheless it is choice treatment for cancers of the balls, girly bits, lungs, lymphs and tummy tum tum. Most recently, it cured Lance Armstrong of testicular cancer, which had nothing to do with anabolic steroids because Lance doesn’t use them (wink wink). My fascination is with the history of the discovery.

lance did it

Cisplatin was identified in the olden days and forgotten, as so many things are, and rediscovered in 1960 after Barnett Rosenberg discovered his electrical fields were making E. coli super-sized and prohibited their cell division to make them into disgusting thingiees (top figure is normal, bottom figure is not). The real genius of Rosenberg was not this serendipitous discovery but the control experiments used to figure out what was causing this effect. Oddly, it was the platinum electrodes, first oxidized by electrolysis to Pt+2 which then reacted with the bacterial growth media which contained both sodium chloride and ammonium salts. Let’s give three hoorays for Cisplatin! HOORAY HOORAY HOORAY.