Prozac, the anti-cancer drug?

It’s common for cancer patients to be prescribed antidepressants as a means of helping them cope with an obviously traumatic diagnosis. But researchers in Israel have found that the selective serotonin-reuptake inhibitor Prozac (generic name fluoxetine) can increase the effectiveness of a common anti-cancer agent, doxorubicin, by tenfold.

A study [Dr. Dan Peer of the Department of Cell Research and Immunology at Tel Aviv University] and his colleagues recently completed validates that Prozac dramatically enhances the effectiveness of a widely used anti-cancer drug.
“The good news is that the medical community won’t have to wait – Prozac can be used for this purpose right away,” says Dr. Peer, noting that doctors in the U.S. already prescribe it to treat depression in chemotherapy patients.
“Prozac is a very interesting non-specific blocker of cancer resistance,” says Dr. Peer, whose study focused on colon cancer and the anti-cancer drug doxorubicin.
In their laboratory experiments, the Tel Aviv University scientists led by graduate student Mirit Argov together with Prof. Rimona Margalit, found that Prozac enhanced doxorubicin’s efficacy more than 1,000%. Prozac, in effect, worked to block the cancer drug from leaving the interior of the cancer cell and poisoning the healthy non-cancerous cells that surrounded it.
In animal models, a mild doxorubicin-fluoxetine treatment combination slowed down tumor progression significantly. These results suggest that pairing Prozac with chemotherapeutic drugs to curb drug resistance warrants further clinical study, says Dr. Peer.

It would be interesting to have more information on the exact mechanism of action involved here. At first I assumed that fluoxetine had been found to slow hepatic metabolism of doxorubicin or something like that, but it appears that fluoxetine’s “wingman” effects on the anticancer agent are indeed direct.
The study results will be published in Cancer Letters.

3 thoughts on “Prozac, the anti-cancer drug?”

  1. Interesting. in the Cancer Letters paper (now published online) they suggest that fluoxetine is acting by blocking the activity of the drug resistance protein P-glycoprotein, and according to their earlier work it can directly inhibit the activity of several multidrug resistance proteins
    Inhibiting multidrug resistance proteins should allow higher intracellular concentrations of doxorubicin to be achieved, enhancing anti-tumour effects and permitting lower doses to be used. Considering the serious toxicity associated with higher doses of doxorubicin this would be very useful.
    It’s also worth noting that the doses of fluoxetine used were equivalent to a quarter of the lowest dose used in treating depression, so hopefully while reducing doxorubicin toxicities it shouldn’t be adding any fluoxetine toxicity.

  2. How is this any different than verapamil? There are a number of marketed drugs that inhibit mutidrug resistance protein and none are still being looked at seriously (see this review). Inhibition of multidrug resistance is one of those things that sounds great, but despite plenty of in vitro success, there hasn’t been anything more than hints that it could be clinically useful.

  3. Well fluoxetine is significantly more potent and less toxic than the 1st generation multidrug resistance inhibitors such as verapamil, so there shouldn’t be such a need to reduce the dose of doxorubicin (or whatever drug is used) to compensate for drug interactions. Hopefully it can avoid the problems they encountered, and because it’s already licensed for other uses it should be easier to start clinical trials than is the case for other MDR inhbitors that are under development.
    I reckon it’s at least worth trying, since if it still doesn’t work and no dose limiting toxicities are the problem than we can clearly state that inhibiting MDR doesn’t help much…at the moment it hasn’t really been given a proper go.

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