Synthetic Molecule Makes Cancer Self-Destruct

Before It’s News – by Alton Parish

Researchers from The University of Texas at Austin and five other institutions have created a molecule that can cause cancer cells to self-destruct by ferrying sodium and chloride ions into the cancer cells.

These synthetic ion transporters, described this week in the journal Nature Chemistry,  confirm a two-decades-old hypothesis that could point the way to new anticancer drugs while also benefitting patients with cystic fibrosis.  

Synthetic ion transporters can induce apoptosis by facilitating chloride anion transport into cells.

Credit: University of Texas at Austin

Synthetic ion transporters have been created before, but this is the first time researchers have shown them working in a real biological system where transported ions demonstrably cause cells to self-destruct.

Cells in the human body work hard to maintain a stable concentration of ions inside their cell membranes. Disruption of this delicate balance can trigger cells to go through apoptosis, known as programmed cell death, a mechanism the body uses to rid itself of damaged or dangerous cells.

One way of destroying cancer cells would be to trigger this innate self-destruct sequence by skewing the ion balance in cells. Unfortunately, when a cell becomes cancerous, it changes the way it transports ions across its cell membrane in a way that blocks apoptosis.

Almost two decades ago, a natural substance called prodigiosin was discovered that acted as a natural ion transporter and has an anticancer effect.

Since then, it has been a “chemist’s dream,” said Jonathan Sessler, professor in The University of Texas at Austin’s College of Natural Sciences and co-author of the study, to find “synthetic transporters that might be able to do exactly the same job, but better, and also work for treating diseases such as cystic fibrosis where chloride channels don’t work.”

Sessler and his collaborators, led by professors Injae Shin of Yonsei University and Philip A. Gale of the University of Southampton and King Abdulaziz University, were able to bring this dream to fruition.

The University of Texas members of the team created a synthetic ion transporter that binds to chloride ions. The molecule works by essentially surrounding the chloride ion in an organic blanket, allowing the ion to dissolve in the cell’s membrane, which is composed largely of lipids, or fats. The researchers found that the transporter tends to use the sodium channels that naturally occur in the cell’s membrane, bringing sodium ions along for the ride.

Gale and his team found that the ion transporters were effective in a model system using artificial lipid membranes.

Shin and his working group were then able to show that these molecules promote cell death in cultured human cancer cells. One of the key findings was that the cancer cell’s ion concentrations changed before apoptosis was triggered, rather than as a side effect of the cell’s death.

“We have thus closed the loop and shown that this mechanism of chloride influx into the cell by a synthetic transporter does indeed trigger apoptosis,” said Sessler. “This is exciting because it points the way towards a new approach to anticancer drug development.”

Sessler noted that right now, their synthetic molecule triggers programmed cell death in both cancerous and healthy cells. To be useful in treating cancer, a version of a chloride anion transporter will have to be developed that binds only to cancerous cells. This could be done by linking the transporter in question to a site-directing molecule, such as the texaphyrin molecules that Sessler’s lab has previously synthesized.

The results were a culmination of many years of work across three continents and six universities.

“We have demonstrated that this mechanism is viable, that this idea that’s been around for over two decades is scientifically valid, and that’s exciting,” said Sessler. “We were able to show sodium is really going in, chloride is really going in. There is now, I think, very little ambiguity as to the validity of this two-decades-old hypothesis.”

The next step for the researchers will be o take the synthetic ion transporters and test them in animal models.

Sessler’s co-authors are Sung-Kyun Ko (Yonsei University and Korea Research Institute of Bioscience and Biotechnology); Sung Kuk Kim, Andrew Share and Vincent Lynch (UT Austin); Jinhong Park and Wan Namkung (Yonsei University); Wim Van Rossom and Nathalie Busschaert (University of Southampton); Philip Gale (University of Southampton and King Abdulaziz University); and Injae Shin (Yonsei University). Sung-Kyun Ko and Sung Kuk Kim were the lead authors on this study. Sessler, Gale and Shin were the corresponding authors.

This work was supported by the National Creative Research Initiative program in South Korea; the Office of Basic Energy Sciences in the U.S. Department of Energy; and the Chemical Biology Research Center in the Korea Research Institute of Bioscience and Biotechnology.

Contacts and sources: Steve Franklin, University of Texas at Austin

7 thoughts on “Synthetic Molecule Makes Cancer Self-Destruct

  1. ya know the cure is already out there in the form of b17, and Hemp resin oil which do the same thing. Wonder why b.i.n. doesn’t report that.

    1. Funny you should mention B17, Paul…
      I stopped by a RiteAid yesterday, while enroute elsewhere. I could not find any there. The women working there couldn’t find it on their list, and had never heard of it. I made a bad joke by saying ‘not the airplane’, which went over their heads just as quick as my inquiry about the supplement. I’ll find it, eventually. (I always look local before considering anything online) We have a bulk-food/general nutrition retailer 20 minutes away that usually has these kinds of things, just not the resins you mentioned. They do have hemp seed galore, though. (cripes, who doesn’t?) 🙂

      1. the resin oil is not allowed. it is a considered controlled substance buy our wonderful leaders. The b17 i acquire from an on line source that is trustworthy. #1nwohatre knows a lot about b17, and bitter apricot kernels which have been an effective medicine for a long time. btw the kernels taste terrible. 🙂

        1. Holy crap, I just realized that the way I wrote that reply it looks like that vendor has hemp oil, which if she does, it’s not on the shelves near the seeds. I wish she did have it. I think the PA gov. more recently introduced legislation for the medicinal oils… after Governor Corbett said something to the effect that he wouldn’t legalize cannabis even if his grandchild was dying. (paraphrasing here)
          That was a very telling moment when the asshole said that, and as you might expect he realized that’s political suicide to say something that harsh about your own family.
          I don’t know where his “opponent” Wolf stands on the issue. (like most, he probably represents ‘big money’)

          Anyway, thanks Paul. If I can’t find the B17 I’ll let you all know somehow. I like to visit that store I mentioned, as they are Mennonite owned… no Sunday sales of course! I live close to Amish and actually worked with some for a few months. That was quite an experience, and in stark contrast to my old line of work.

  2. I wrote the governor of West Virginia with regards to hemp oil.

    No response . . still holding breath.

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