Dr. Weeks’ Comment: I will save my comment until after you have read this new report on a precursor drug for aspirin being so helpful. ~
A novel aspirin prodrug inhibits NFκB activity and breast cancer stem cell properties
Introduction
Activation of cyclooxygenase (COX)/prostaglandin and nuclear factor κB (NFκB) pathways can promote breast tumor initiation, growth, and progression to drug resistance and metastasis. Thus, anti-inflammatory drugs have been widely explored as chemopreventive and antineoplastic agents. Aspirin (ASA), in particular, is associated with reduced breast cancer incidence but gastrointestinal toxicity has limited its usefulness. To improve potency and minimize toxicity, ASA ester prodrugs have been developed, in which the carboxylic acid of ASA is masked and ancillary pharmacophores can be incorporated. To date, the effects of ASA and ASA prodrugs have been largely attributed to COX inhibition and reduced prostaglandin production. However, ASA has also been reported to inhibit the NFκB pathway at very high doses. Whether ASA prodrugs can inhibit NFκB signaling remains relatively unexplored.
Results
While we identified multiple ASA prodrugs that are capable of inhibiting the NFκB pathway, several were associated with cytotoxicity. Of particular interest was GTCpFE, an ASA prodrug with fumarate as the ancillary pharmacophore. This prodrug potently inhibits NFκB activity without innate cytotoxicity. In addition, GTCpFE exhibited selective anti-CSC activity by reducing mammosphere growth and the CD44 + CD24 − immunophenotype. Moreover, GTCpFE pre-treated cells were less tumorigenic and, when tumors did form, latency was increased and growth rate was reduced. Structure-activity relationships for GTCpFE indicate that fumarate, within the context of an ASA prodrug, is essential for anti-NFκB activity, whereas both the ASA and fumarate moieties contributed to attenuated mammosphere growth.
Conclusions
These results establish GTCpFE as a prototype for novel ASA-and fumarate-based anti-inflammatory drugs that: (i) are capable of targeting CSCs, and (ii) may be developed as chemopreventive or therapeutic agents in breast cancer.
END OF ARTICLE
Dr. Weeks’ Comment: Good news? Yes! Now. Want better news? Here it is..
Take aspirin! Really, just take aspirin! You read it here first. Yup – cheap and effective aspirin. Has the doctor treating your prostate cancer too you to take aspirin? Has the oncologist treating your breast cancer told you to take aspirin? Has your oncologists told you that taking aspirin BEFORE chemotherapy treatments makes the chemotherapy more effective and helps reduce side-effects? Nope. Aspirin is too cheap for corporate doctors (i.e. doctors who work on you but who work for corporations) to recommend. Aspirin, when taken appropriately is just as beneficial as the new aspirin pro-drug GTCpFE at a fraction of the price. (Note: when not taking appropriately, aspirin and other over-the-counter non steroidal anti-inflammatory drugs (NSAIDs) can cause liver and kidney damage, macular degeneration and death by bleeding in your lungs or your gut which is why aspirin, if invented today, is potentially lethal enough to only be available by prescription.)
This is yet another shameful example of Big Pharma not using their billions to advise us of what really works (anti-inflammatory diet, exercise to oxygenate the blood and restore Krebs cycle to aerobic respiration and additional careful use of over-the counter anti-inflammatory agents like aspirin. No – Big Pharma and corporate doctors are focused on profits and benefit when you buy the patented and expensive “pro-drug” of aspirin. Why not just Eat the seeds! and take something which is more “centsible” (safer, more effective and more cost effective) than aspirin? (which, by the way comes with a satisfaction guarantee or your money back on the first box purchased for $65)
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