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Killing two birds with one stone: a new (nano) curcumin and doxorubicin study

Posted Jul 16 2012 6:18am

Okay, this is a bit of exciting news…A new study that gives us a fine and promising example of integrative oncology…

And I say: it’s about time!

A group of Johns Hopkins researchers has recently come up with a way to combine curcumin (nanocurcumin) WITH doxorubicin (nanodoxorubicin). Their invention, called “NanoDoxCurc” (NDC), is a huge improvement over doxorubicin used by itself. For many reasons, as we will see.

Finally, a chemo drug PLUS curcumin…stuck together inside a nanoformulation. (And yes, nanoformulation appears to be a proper word.) 

As we can see from the full study (which you can access here: http://goo.gl/YFpY9 ), the presence of curcumin lessened at least two of the well-known and very serious side effects of doxorubicin, namely, its extremely harmful effects on the heart and bone marrow. 

It also overcame the stubborn chemoresistance of three different cancer cell lines, including a myeloma one. Multi drug resistance, as we know, is a huge problem in cancer treatment. HUGE.

The study begins with a discussion of chemoresistance and the related issue of doxorubicin dose escalation. When cancer cells become resistant to doxorubicin, you can increase the chemo dose and overcome that resistance to some degree, but this carries with it a series of problems, including damage to the heart (e.g., congestive heart failure) and bone marrow suppression. Damned if you do, damned if you don’t…

Many attempts, the authors write, have been made to overcome chemoresistance with synthetic substances (small molecules and antibodies), but most have failed.

And that brings us to this exciting bit: Natural products are gaining attention in MDR inhibition due to their low cytotoxicity profiles. For example, the role of the phytochemical curcumin (derived from Curcuma longa) in inhibiting multiple MDR pumps in cancer cells has been widely studied, including in combination with DOX. (DOX = doxorubicin; MDR = multidrug resistance). As I said, ABOUT TIME! 

Because of curcumin’s well-known poor bioavailability, the researchers developed a polymer nanoparticle formulation of curcumin (NanoCurc or NC) that significantly enhances the systemic bioavailability of this agent. (I WAAAAAANT SOME! But it seems as though it isn’t currently for sale…?) And then they combined NC with a nanoformulation of doxorubicin (or ND) and, poof!, created NDC.

The authors discovered that their nanocurcumin was able, and I quote, to overcome DOX resistance in a variety of human and murine cancer cell lines in vitro as well as in vivo. Notably, we also find that systemic NDC shows no evidence of cardiotoxicity or bone marrow suppression, even at cumulative dosages at which such demonstrable adverse effects are readily observed in free DOX or Doxil®-treated mice, thus overcoming some of the greatest limitations of DOX-based chemotherapy. So, even at high doses, the mice treated with NDC were okay. Isn’t that amazing?

Jumping to the “Results,” now. Here we can read that treating the drug resistant cancer cell lines (including a myeloma one, as I mentioned) with NDC reduced the drug resistance of the cancer cells dramatically compared to nanodoxorubicin alone. Dramatically! 

Before I go on, I have to say that I really hate to talk/write or even think about mice in a lab setting, especially whenever toxicity is mentioned…but I must.

Please check out Figure 4 on page 6: this shows that the mice treated only with doxorubicin ended up with HOLES in their little hearts (ugh). Those treated with the nanodoxcurcumin formulation instead didn’t have any heart damage.

But how well did this new formulation work against the three different types of cancer? : NDC SIGNIFICANTLY DECREASED the proliferation of all of the cell lines. :)

And check this out: Interestingly, NC alone showed greater potency than ND in all three DOX-resistant cell lines. Wowsers! :)

Well, there is lots more info in the Results section, such as glutathione levels and body weight. For example, the mice on ND and NDC didn’t lose a lot of weight compared to the control group, which is important. Later on, you see, we discover that the mice on DOX and DOXIL (the latter is a liposomal formulation of DOX) lost of their body AND heart weight! Eeeeeekkkk!

Another interesting tidbit concerns hemoglobin (Hb) levels. Compared to the 12.5 g/dL of the control group, the Hb of the mice in the DOX group dropped to 7.5 g/dL. They became anemic, in other words. Their lymphocyte counts were also very low, leaving them vulnerable to infections. Nothing of the sort occurred in the ND and NDC-treated creatures. So that’s another important finding…

Nanocurcumin also protects healthy cells from damage: Our recent studies with nanoparticulate curcumin have confirmed its ability to ameliorate oxidative damage to non-neoplastic tissues, such as in hepatocytes and neuronal cells, through induction of a favorable intracellular redox environment. I’ve posted many times about this particular ability of curcumin, in fact…

Okay, if you don’t have time to read the full study, just skip down to the Discussion. It summarizes all the important bits, such as the following:

  • Nanocurcumin protects the heart from DOX-induced injury.
  • Nanocurcumin also reduces multi drug resistance. Strongly.
  • The new nanocurcumindoxorubicin (= NDC) formulation can whack cancer cells much more strongly than nanodoxorubicin (ND) alone.
  • Hemoglobin and lymphocyte counts in the NDC-treated mice were similar to those of the control group.
  • The NDC-treated mice maintained their body weight and didn’t show any evidence of toxicity. They behaved normally.
  • A group of NDC-treated mice infected with an extremely aggressive and chemoresistant form of leukemia survived 50% longer than mice in the control group and those in the ND-alone group.

I’ll end with an important excerpt: Interestingly, while both ND and NC each showed a degree of tumor growth inhibition, the composite nanoparticle NDC showed nearly complete growth inhibition (>90%) over the duration of the study.

90%…

Written by Margaret

July 16th, 2012 at 12:18 pm

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