Nitric Oxide (smog) Cures Cancer?

Or maybe causes it….

So, under California Prop. 65 rules, if being treated for cancer with NO gas, you would need to be told your medicine causes cancer…

The good NO treatment:

Nitric Oxide:
Just say NO to Cancer and Much More

Nitric oxide (NO)—a simple molecule consisting of one nitrogen atom and one oxygen atom—is everywhere. Blood vessels use it to relax, neurons use it to communicate, and innate immune cells use it to kill dangerous invaders. NO researchers won the Nobel Prize in 1998, barely a decade after its identification as the biological activity known as endothelial-derived relaxing factor (EDRF). As the initially controversial evidence began to accumulate that NO is a key player in several biological processes, Larry Keefer, Ph.D., Chief of CCR’s Laboratory of Comparative Carcinogenesis, was ready with the tools to manipulate it for biomedical research. An organic chemist working on NO-related chemistry as a means to understand and ultimately prevent the carcinogenic effects of the nitrosamines found in a variety of foodstuffs, environmental sources, and manufacturing processes, Keefer was poised to jump into the NO fray with the first reliable chemical donor with which to study the effects of authentic NO in culture and in vivo. Since then, he has initiated several collaborations to develop and study agents that can selectively target NO’s power to destroy cancerous cells. His goal is to see one of these agents enter the clinic.

A volatile gas on its own, nitric oxide (NO) is produced where it is needed in the body, and it cannot be directly administered to most biological tissues. Instead, it must be released from other compounds, as in the case of nitroglycerin, which was used to treat heart pain a hundred years before the mechanism producing dilation of blood vessels was shown to be NO.

“My group is [almost entirely] chemists,” said Keefer. “We know how to make compounds, make them pure, and design them with specific structural features. That’s been our forte. We try to interest collaborators who know how to do the rest of it.” One of his most fruitful collaborations has been with University of Utah oncologist Paul Shami, M.D., to study the use of NO to fight cancer.

NO to Leukemia

Shami demonstrated several years ago that acute myeloid leukemia cells are particularly sensitive to NO toxicity at concentrations of a NO-releasing drug substantially lower than those that safely maintain normal healthy endothelial or liver cells.

“NO had long been known as a toxic air pollutant, cigarette smoke constituent, and precursor of carcinogenic nitrosamines. But as its numerous bioeffector roles attest, NO turns out to be essential for proper health just about everywhere in your body,”
explained Keefer. “So, evolution has provided our cells with ways to deal with its toxic potential.” Shami’s leukemia cells had apparently lost some of that ability. This led him to the hypothesis that administering a NO-releasing drug into the general circulation might preferentially eliminate the NO-sensitive leukemia cells without collateral harm to normal tissues. This proved to be the case in a mouse xenograft model of leukemia—a research model in which human cancer cells are grafted under the skin of mice with impaired immune systems to prevent rejection of the foreign graft. The lead compound Shami identified, JS-K, cut the growth rate of the mice’s tumors in half without any apparent toxic effects; it also induced more necrotic cell death, relative to controls, in the tumor mass that remained.

Having learned of Shami’s success with the in vivo leukemia model, Tanyel Kiziltepe, Ph.D., and Kenneth Anderson, M.D., at Harvard Medical School, demonstrated that JS-K also inhibits proliferation of human myeloma cells in vitro as well as in xenograft models. Because of JS-K’s cell specificity, the doses required to see an effect in mice did not, as expected, cause major changes in vascular tension. The researchers have also studied the mechanisms through which JS-K damages cancer cells and have found evidence for NO-induced DNA damage leading to apoptosis. “I can’t put together the whole story on the mechanism yet,” noted Keefer. “You look at the structure and chemistry, and there are clearly other pathways by which the compound can be active.” Nonetheless, the preclinical evidence is mounting for JS-K’s potential as a novel anticancer agent. In a paper published earlier this year in Leukemia Research, the team demonstrated that JS-K has a synergistic effect with the antileukemia drug cytarabine in inhibiting proliferation of leukemia cell lines. Shami, in the meantime, has founded a biotechnology company with a confidently optimistic name—JSK Therapeutics.

The efficacy of JS-K appears to extend beyond leukemia and multiple myeloma cells. Similar cytostatic effects have been observed in rodent liver and prostate cancer models.
Keefer is also collaborating with Lucy Anderson, Ph.D., Head of the Cellular Pathogenesis Section at CCR, to study JS-K in the multiple human lung cancer cell lines that she and her colleagues have characterized for NO research. Working across the two laboratories, Research Associate Anna Maciag, Ph.D., has unpublished data demonstrating that JS-K is not only effective against lung cancer cells but that it also appears to have an even greater potency in lung cancer cells that have high levels of reactive oxygen species (ROS). “Now we’re talking about personalized medicine,” commented Keefer. “If a tumor contains high levels of ROS, perhaps it will be an ideal candidate for our drug.”

Then, the other side of the coin:

Nitric oxide shown to cause colon cancer

Study offers proof of compound’s role in disease

Anne Trafton, News Office
January 19, 2009

Researchers long ago established a link between inflammation, cancer and the compound nitric oxide, which may be produced when the immune system responds to bacterial infections, including those of the colon. However, the exact nature of the relationship was unknown –Â until now.

Scientists from MIT’s Division of Comparative Medicine and Department of Biological Engineering have found that nitric oxide produced by inflammatory cells during bacterial infection can cause colon cells to become cancerous. The finding suggests that blocking the compound may help prevent or treat colon cancer, the third most common form of cancer in the United States.

The researchers, led by James Fox, director of the Division of Comparative Medicine (DCM), report their findings in the Jan. 19 online edition of the Proceedings of the National Academy of Sciences.

Many years ago it was discovered that gastrointestinal infection by H. pylori is often linked to cancer in humans; a related bacteria called H. hepaticus has similar effects in mice.

So there you have it. In California, just like coffee, cancer treatment with NO would require a notice that your treatment causes cancer…

But wait, there’s more!

Since Nitric Oxide is fundamental in animal metabolism and control, and also present in plants: ALL plant and animal products MUST carry a California Prop. 65 warning that they contain chemicals known to the State Of California to cause cancer or reproductive harm. The law just mandates it, no questions about concentration or actual effect are applied. If the stuff is there, the sign MUST go up. So make sure ALL food is so labeled. If not, it’s a $2500 / person / day of “exposure” fine. Since “everybody eats”: that’s $2500 per person per day for every person in California, in fines just waiting to be laid and collected. Get cracking you Lawyers!

Sigh. So much stupid. So little mind…

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About E.M.Smith

A technical managerial sort interested in things from Stonehenge to computer science. My present "hot buttons' are the mythology of Climate Change and ancient metrology; but things change...
This entry was posted in Biology Biochem, Science Bits and tagged , , , , , . Bookmark the permalink.

13 Responses to Nitric Oxide (smog) Cures Cancer?

  1. Sandy MCCLINTOCK says:

    Well said ;) . …and then there is the impact on heart disease…
    “Though NO’s structure is simple, nitric oxide is now regarded as the most significant molecule in the body, absolutely crucial to your well-being. I am convinced that the nitric oxide can age-proof your cardiovascular system, keeping it much fitter than your chronological age would indicate.” “Repairing the damage wrought by cardiovascular disease without risky and often ineffective surgery had long been considered impossible. I was awarded the noble prize in Medicine for making that thinking obsolete. Now we know we can reverse cardiovascular impairment naturally – with the body’s internally manufactured ‘wonder drug’ nitric oxide.
    ”Louis Ignarro, Ph.D., Nobel Laureate in Medicine (1998) and author ‘No More Heart Disease’

  2. Eric Fithian says:

    Gary North’s “Three Laws of Bureaucracy”
    1. Some bureaucrat will inevitably enforce an official rule to the point of imbecility.
    2. To fix the mess which this causes, the bureaucracy will write at least two new rules.
    3. Law #1 applies to each of the new rules.

    Rinse & Repeat …

    It sounds as though the way to prevent NO prompting malignancy in the colon, that bacterial infection should be minimized, or inflammation be reduced….

    Could be a Catch-22: Have to be in to get in….

    Mayhap I need more Vitamin C and sunlight…?
    And a lead-free tinfoil hat!

  3. Graeme No.3 says:

    Reminds me of the temporary status of Coca Cola in Australia in the 1970’s. As new labelling laws were introduced a public servant in Qld. Ignored the exemption for products containing less than 0.5% phosphoric acid. As a consequence Coca Cola found that they were expected to sell their product in a black plastic bottle embossed POISON and with a label stating IF SWALLOWED SEEK MEDICAL ADVICE.
    I believe that Coca Cola exerted a good deal of pressure on the Politicians nominally in charge of the Department, and a number of public servants, initially uninterested in correcting the error, were suddenly woken up to a threat to their future career prospects.

  4. pouncer says:

    I become more and more tempted to learn Spanish, tint my hide, join “La Raza” and help the region of Aztlan (a.k.a. California) secede and form a new and fully independent nation, unhindered by the sanity of paler, Anglo-centric, regions East and North.

  5. cdquarles says:

    I have long said that cancer ‘can not be cured’ because it is a disease of long life and of each individual’s local immune system. The very processes that guide multicellular development from the fertilized egg cell to adulthood are capable of destroying said body from within. Mortal man, doomed to die. And the span of a man’s years shall be 120. Given that one can shorten this, we have the expectancy of 3 score and 10.

    For 20 years I’ve had colitis. For more years I’ve had issues with an overactive immune system and several family members have had complications from various infections. I have been on immune modulators for 20 years. One of these days, I’m going to get that call after a colonoscopy with the dreaded “C” word, if I live long enough. Most in my family make it to the mid 70s and up to the mid 90s. One made it to 106.

  6. E.M.Smith says:


    You might want to consider a fasting regime to remove any potential allergens from your digestive tract and starve out of existence most of the gut flora and fauna; then slowly add back in one food at a time and see: IF things are better; then IF any particular food(s) when added cause issues.

    I’d likely use an unfamiliar food for the first one added back so the immune system was more naive about it. Goat Yogurt (plain) is pretty much a complete food, has only beneficial bacteria in it, and is unlikely to be an issue. Then you can start adding some simple jams to it the 2nd or 3rd day to improve the flavor and interest (and see if added sugars causes a yeast flare up that’s related to the problem…). Alternatively, I’d start with eggs and butter (as you can’t make decent scrambled eggs without butter ;-) and it, too, is a complete nutritional package. Then add chicken in a day or two. After that, I’d add leafy vegetables.

    FWIW, I did a very similar “elimination diet” a couple of times. Found out “Cow Stuff” causes me to have an arthritic flare up. Some protein fragment from cows does not completely get broken down in digestion and gets incorporated into the wear points as part of repair, then the immune system says “What’s this cow stuff doing here?” and attacks it… That’s the theory anyway.

    I’d been listening to a tech radio show and they had a panel of immunology doctors on discussing allergies and food issues. The panel had an interesting observation: THE thing that sets off your allergic reaction is often NOT the main problem. There will often be some other factor that’s getting the immune system keyed up, but not over the top; then just about anything that comes along and causes any added response “sets you off”. They listed things like grasses and pollen as the triggers, but diet as often being part of the basic immune stimulus. Pointing out the top 5 foods causing allergic issues as usual causes. IIRC it was something like: Wheat, Dairy, Seafood, Eggs, Nuts. Some folks divide seafood into fish and shellfish and some folks split out peanuts from generic nuts; that brings it up to 7. Since soy sets off a lot of folks, sometimes that’s added to make up the “big 8”. In theory the “first food” ought to avoid them.

    I started chicken as my first food. (I also allowed some oil to fry it in…) Second food I added was potatoes. When I added milk I flared… Oddly, I did not react with just butter, so buttered mashed potatoes stayed in while I added the rest of the foods. Generally speaking, few folks react to any greens or roots other than potatoes. (Potatoes have starches that can feed a yeast problem and some folks react to anything with solanine in it. Potatoes & Tomatoes.) It takes about 2 weeks for your immune response to fade (or get keyed up) and I was surprised to find that 2 weeks of “nothing but chicken” was hard to do… as I really like chicken. OTOH, I stopped sneezing and wheezing… The second week of just chicken & potatoes was a bit easier. By the time I had 4 ingredients to work with it was easy.

    I based this on the diet from a book called “The Arthritics Cook Book” by a Dr. Dong. (There’s another book with the same title that is NOT the right one…) He had very good success treating his patients with a diet of fish, selected vegetables (i.e. not tomatoes or other vegetables that are actually fruits) and rice. I blended his approach with the process I learned from that panel of doctors discussing auto-immune diseases and diet (and elimination diets).

    My guess is that IF colitis has an immune component, it would be a similar process OR a reaction to some guy flora / fauna and so starving them out and applying new might improve things. IIRC, there has also been some success with “fecal transplants” where they move some shit from a person without problems (so a better mix of gut bacteria) to a person with problems. In the Government Over-regulation Department: The FDA now mandates all their rules must apply to any shit used in that process…. Yes, you MUST use Government Certified shit… No joke… at least not by me…

    Hope some of this is helpful.

  7. philjourdan says:

    Life expectancy raced forward from the mid 19th to the mid (late) 20th century. Now it is receding. The reason?

    Ask California.

  8. cdquarles says:

    Not interested in that, EM. I am lactose intolerant, which began 30 days after my 17th birthday, but otherwise food does not give me trouble. I am old, though not quite as old as you are; and grew up with all of the ‘childhood’ illnesses. I have had many of these cross-react. Been there, done that, got the T-shirt. Interestingly, poison ivy does not do much to me, though hymenoptera stings do; and I live in Fire Ant territory.

    WRT yogurt, I love it.

    If you ask me, food ‘allergies’ are real, but over-diagnosed.

  9. cdquarles says:

    On the other hand, I am very fond of rice and Asian cuisine. Yeah, I have to watch the soy, though.

  10. cdquarles says:

    The other thing I try to do is mix it up. I still need the modulators, though. I suspect what got me was moving into an area where the bugs were different but not different enough, so I was bitten by the cross-reaction. I still get flares from time to time, with the last one just before mom died. So yeah, stress is an immune modulator, too.

  11. John F. Hultquist says:

    Here is a dietary supplement:
    neo40: LINK

    Contains Beet Root powder,Hawthorn Berry extract, L-citrulline, Sodium Nitrite

  12. H.R. says:

    Okay. On the previous thread, my little jab at California requiring Breathe signs may not be so farfetched after all.

    If your license plate ends in an odd number, you breathe on even-numbered days to take IN nitric oxide and stop breathing on odd-numbered days to AVOID inhaling nitric oxide.

    If your license plate ends in an even number, you breathe on odd-numbered days to take IN nitric oxide and stop breathing on even-numbered days to AVOID inhaling nitric oxide.

    That seems about right since it will satisfy Gary North’s “Three Laws of Bureaucracy” that Eric Fithian posted above.

    In order to simplify things California will tie in breathing to trash pickup and lawn watering days. So on your days to breathe, your trash will be picked up, but you can’t water your lawn, unless your adjusted gross income in the previous year was between $32,000 and $65,000 and you are single head of household or married and filing separately, but only if you itemized deductions.

    And remember, when they outlaw breathing, only outlaws will breathe.

  13. E.M.Smith says:


    You do understand California!

    We have mandated “no watering” times, but also “urban blight” laws that say you must keep nice green tidy lawns.

    We have gasoline at $4 / gallon for super in San Francisco, yet you get to spend 2 to 3 hours commuting to work as it costs too much to live there.

    Your company can be fined for losing email and your CIO sent to prison, but you can be put out of business if you have the wrong things said in your email.

    CEOs are required to give quarterly “Guidance” on expected earnings, but if that turns out to be unexpected your stock price can plunge, or if it is what was expected but then some surprise causes things to change so it’s not true any more the SEC can take your money away and toss you under the bus, or in one headed to a Federal Institution.

    You MUST hire the right number and mix of any and all Special Protected Classes (women, blacks, Hispanics, Asians, etc. including old folks – over 50 IIRC) but the only people NOT in a protected class are Non-Hispanic Christian Straight White Males between 18 and 50. Go figure. If ANY ONE % isn’t right, you can be sued. But you can’t discriminate in hiring and are supposed to just hire the best candidate. So if you need an additional Asian woman to get your stats right, you can’t go looking for an Asian woman… but if you don’t hire one you can be punished.

    I could go on, but I’m out of Scotch and I really need pain killers if I start to think about it too much.

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