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How wild cabbage bred several varieties with anticancer properties

Every so often, a new treatment or trial drug shows overwhelming promises that, unfortunately, fail to materialize right away. The last of such announcements states that a small-molecule oral cancer drug kills 100% of solid tumors across 70 cancer types with no discernible side effects.

The results have been achieved in lab and rodent tests, though human trials are underway.

The new drug is a small molecule that interferes with the critical molecule boosting cancer replication, PCNA, preventing it from attaching against each other and building the scaffolding of invasive cell replication. According to a headline by Fierce Biotech, this PCNA inhibitor “works like a snowstorm shutting down an airport.”

Market Scene, painting by Pieter Aertsen (1569)

As the phase 1 trials are on their way on this new drug, headlines already promise what seems to be no less than the medical equivalent of reaching the singularity: a “cancer-killing pill” that appears to “annihilate” solid tumors could make the most significant medical impact in modern history.

Fighting the Emperor of all maladies

Before we read the cautionary articles that could follow the overly optimistic, game-changing ones being published now, the breakthrough seems important enough to share the optimism as it is now being tested on humans: are we now closer to the moment in which people affected by advanced-stage cancer will have the chance to fight their gloomy prospects with a non-invasive treatment capable of destroying solid tumors?

While searching for the ultimate medical solutions that could help cure the second most common cause of death in the US after heart disease, its prevention is also evolving fast thanks to immunotherapies, which use the power of the immune system to fight such a complex and wide-ranging malady, according to Siddhartha Mukherjee, author of a 2010 book with the allure of epic battles:

“In a sense, this is a military history—one in which the adversary is formless, timeless, and pervasive. Here, too, there are victories and losses, campaigns upon campaigns, heroes and hubris, survival and resilience—and inevitably, the wounded, the condemned, the forgotten, the dead. In the end, cancer truly emerges, as a nineteenth-century surgeon once wrote in a book’s frontispiece, as “the emperor of all maladies, the king of terrors.”

Nature vs. nurture

Prevention is never as consequential and quantifiable as treatment can be; despite the efforts by oncologists to acknowledge in the last years that cancer is not one single malady, nor one that can be easily isolated from the intricacies of the human body, misunderstandings persist in establishing unequivocal causalities between genetic predisposition, ambient stressors, and lifestyle choices affecting anybody’s odds of developing some cancer on their lifetime.

The medical community has determined nonetheless the choices that can help prevent any cancer or increase the odds of any cancer diagnosed early on: avoiding tobacco and heavy pollution, limiting ultraprocessed foods and drinks, protecting our skin from persistent radiation, or avoiding as much as possible the contact with substances known to cause cancer.

But defining prevention by the things people should avoid taking or doing is a reductionist and compartmentalized remnant of malady treatments that eluded more holistic approaches to the organism, nervous system, and environment.

Oncologists have been making an effort in the last few years to integrate in their practice the evidence liking proactive ways of taking care of ourselves (physically and mentally) as a decisive factor to have better health and elude cancer even when there’s a strong genetic predisposition to develop some tumor.

A very particular healthy choice

Despite the growing evidence of the impact of certain foods and lifestyle choices in preventing cancer and improving the odds of its cure after early detection, medical advice is still generalist, conservative, and merely prescriptive. “Eating a healthy diet” can mean different things to different people, and “being physically active” can be misinterpreted as well.

Among the unprocessed food linked to cancer prevention by studies and evidence are those antioxidant-rich like berries (remember, tomatoes are berries too, gigantic ones for that matter), fruits, nuts, seeds, vegetables, or some traditionally-processed foods (certain vegetable oils, fermented or germinated foods).

Several plants domesticated early on is an outlier both for their availability and the number of functional properties with anticancer properties. Despite its variability, the genus Brassica includes cruciferous vegetables, cabbages, and mustard plants. Native from Western Europe, the Mediterranean basin, and temperate regions of Asia, it was already edible in different distinctive cultivars during Greek and Roman times, and recent studies link its early domestication to the Eastern Mediterranean.

Brassica oleracea and its wild cultivars

With at least 30 wild species and hybrids still in cultivation, the genus is so beneficial and versatile that each cultivar has exploited the edible properties and size of the root (turnip), leaves (cabbage, kale), stems (kohlrabi), flowers (broccoli, cauliflower), seeds (for oil or mustard production), or buds (Brussels sprouts, cabbage).

More precisely, one single plant species, Brassica oleracea or “wild cabbage,” is the ancestor of broccoli, cabbage, Brussels sprouts, kohlrabi, kale, cauliflower, collard greens, Savoy cabbage, kohlrabi, and gai lan. A jack of all trades, indeed.

The Brassica oleracea family is rich in vitamins, minerals, fiber, and antioxidants that help reduce inflammation, regulate blood sugar levels, and reinforce the immune system —hence its praise as a vital part of any diet aiming at reducing the risk of several cancers.

Some of Brassica oleracea’s most pervasive cultivars (cultivars are varieties developed by desired traits, remaining essentially the same plant)

Several studies acknowledge the status of Brassica oleracea as a “preventive biomaterial” for cancer:

“Broccoli contains a number of functional properties including anticancer activity. Sulforaphane, an active potential component in broccoli and other isothiocyanates, showed evidence to inhibit cancer by interfering with multiple cellular targets and mechanisms.”

Wild cabbage offspring and oxidative stress

Present in cruciferous vegetables such as broccoli, Brussels sprouts, cabbage, and the other mentioned varieties, sulforaphane is a chemical compound that helps increase blood flow to the organs and brain, reduce swelling, and activate the immune system’s pathways linked to a reduction of oxidative stress (or the inability of our body to properly shield our body from the damage inflicted by free radicals and other oxidative reactions.

The pathways helping reduce oxidative stress will ultimately determine how our body handles cell repair and inflammation. Along with other environmental factors and lifestyle choices, a very high level of damage increases the risk of cancer. Hence the medical interest in studying sulforaphane, the naturally-occurring compound that turns cruciferous vegetables in general—and the family Brassica oleracea in particular—into nutrients of special interest when it comes to preventing and fighting cancer.

That said, studies attest that there’s no clinical evidence showing causation between consuming cruciferous vegetables and preventing or improving the outcome of any early-stage cancer treatment. However, the benefits of sulforaphane in the immune system are attested.

Digesting vegetables rich in sulforaphane could impact the body’s ability to use iodine, used by the thyroid gland to make thyroid hormone, which regulates the body’s metabolism and development.

Domesticating a very useful hardy plant

Exploring the Brassica oleracea family is a culinary feast with positive health consequences. When our ancestors stumbled upon the nutritive (and medicinal?) potential of the oily wild mustard, they welcomed it into their diet. Over time, and since its domestication in the Eastern Mediterranean, the species was selected for as many properties as the plant allows.

Over time, farmers selected variants with the enlarged wanted character: terminal buds, lateral buds, stems, leaves, flowers, roots, and clusters. This process is still ongoing: as recently as in 1993, a Japanese seed shop bred broccolini, a hybrid between broccoli and a traditional Chinese variety, kai-lan.

In his encyclopedic compendium Naturalis Historia, Roman naturalist Pliny the Elder dedicates the book 20 to drugs obtained from common garden plants, the family of “cabbages” among them. He used “brassica” to designate the cabbage-like domestic vegetables. Then he goes on to chapter 33 to enunciate that Cato (quoting Greek sources, mainly Hippocrates, but some of them fragmentary or fully lost) had already mentioned eighty-seven remedies coming out of cabbages.

Pliny the Elder’s chapter on Brassica

Today, most statements would be considered fallacious, though his diverse mentions make us recall the potential effects of sulforaphane on the immune system:

“It would be too lengthy a task to enumerate all the praises of the cabbage, more particularly as the physician Chrysippus has devoted a whole volume to the subject, in which its virtues are described in reference to each individual part of the human body. Dieuches has done the same, and Pythagoras too, in particular. Cato, too, has not been more sparing in its praises than the others; and it will be only right to examine the opinions which he expresses in relation to it, if for no other purpose than to learn what medicines the Roman people made use of for six hundred years.”

“The most ancient Greek writers have distinguished three1 varieties of the cabbage; the curly cabbage, to which they have given the name of ‘selinoïdes,’ from the resemblance of its leaf to that of parsley, beneficial to the stomach, and moderately relaxing to the bowels; the ‘helia,’ with broad leaves running out from the stalk—a circumstance, owing to which some persons have given it the name of ‘caulodes’— of no use whatever in a medicinal point of view; and a third, the name of which is properly ‘crambe,’ with thinner leaves, of simple form, and closely packed, more bitter than the others, but extremely efficacious in medicine.”

Modernity of an old pharmacopeia

According to Cato (Pliny the Elder goes on), brassica varieties are good for “headache, dimness of the sight, and dazzling6 of the eyes, the spleen, stomach, and thoracic organs, taken raw in the morning, in doses of two acetabula, with oxymel, coriander, rue, mint, and root of silphium.” Due to their strong flavor, Cato recommended dressing them with condiments or even including them in a sauce.

Pliny, the Elder’s mainly fantastic descriptions of Ancient erudition regarding the medicinal use of cabbage-like garden plants, hint nonetheless at the effective pre-modern use of some varieties to treat high-mortality maladies until recently: red cabbage was used as a pectoral (tuberculosis, pleurisy), whereas fermented round cabbage (sauerkraut), especially rich in vitamin C, was successfully used to prevent scurvy in long sea voyages (Captain James Cook included sauerkraut on his long travels. Science would need to wait until the 1930s to establish the link between the chemical ascorbic acid found (vitamin C) and the body’s ability to use carbohydrates, fats, and protein efficiently.

In knowing the relation and benefits of sulforaphane, the beneficial chemical compound found in brassica plants, are we in a similar position as James Cook when he established the correlation between bringing fermented cabbage and the prevention of deadly scurvy during his long voyages? Correlation is not causation.

Until sometimes (just sometimes), it happens to be.