04.2020 | THE SCIENTIST 41sex hormones, insulin, and inflamma-
tory molecules.^4 However, this effect is
only seen if exercise training is accom-
panied by weight loss, and researchers
have not yet established causal direct
links between regular exercise training
and the reductions in the basal levels
of these risk factors.^5 Alternatively, the
anticancer effect of exercise could also
be the result of something that occurs
within individual sessions of exercise,
during which muscles are known to
release spikes of various hormones and
other factors into the blood.
To learn more about the effects of
individual bouts of exercise versus long-
term training regimens, Christine Deth-
lefsen, a graduate student in my labora-
tory, incubated breast cancer cells with
serum obtained from cancer survivors
at rest before and after a six-month
training intervention that began after
patients completed primary surgery,
chemotherapy, and radiotherapy. For
comparison, she incubated other cells
with serum obtained from blood drawn
from these patients immediately after
a two-hour acute exercise session dur-
ing their weeks-long course of chemo-
therapy. Her study revealed that serum
obtained following an exercise session
reduced the viability of the cultured
breast cancer cells, while serum drawn
at rest following six months of training
had no effect.^6
These data suggest that cancer-fighting
effects are driven by repeated acute exer-
cise, and each bout matters. In Deth-
lefsen’s study, incubation with serum
obtained after a single bout of exercise
(consisting of 30 minutes of warm-up,
60 minutes of resistance training, and a
30-minute high-intensity interval spin-
ning session) reduced breast cancer cell
viability by only 10 to 15 percent com-
pared with control cells incubated with
serum obtained at rest. But a reduction
in tumor cell viability by 10 to 15 per-
cent several times a week may add up to
clinically significant inhibition of tumor
growth.^7 Indeed, in a separate study, my
colleagues and I found that daily, vol-
untary wheel running in mice inhib-
its tumor progression across a range of
tumor models and anatomical locations,
typically by more than 50 percent.^8Exercise’s molecular messengers
One prime candidate for helping to
explain the link between exercise and
anticancer effects is a group of pep-
tides known as myokines, which are
produced and released by muscle cells.
Several myokines are released only dur-
ing exercise, and some researchers have
proposed that these exercise-dependent
myokines contribute to the myriad ben-
eficial effects of physical activity for all
individuals, not just cancer patients,
perhaps by mediating crosstalk between
the muscles and other parts of the body,
including the liver, bones, fat, and brain.
The best-characterized myokine is
interleukin-6, levels of which increase
exponentially during exercise in humans.
At least in mice, interleukin-6 is involved
in directing natural killer (NK) cells to
tumor sites. But there are approximately
20 known exercise-induced myokines,
and the list continues to grow. Prelim-
inary studies show that myokines can
reduce cancer growth in cell culture and
in mice. For example, when treated with
irisin, a myokine best known for its ability
to convert white fat into brown fat, cul-
tured breast cancer cells were more likely
to lose viability and undergo apoptosis
than were control cells.^9 A study I led
found that oncostatin M, another myo-
kine that is upregulated in murine mus-
cles after exercise, also inhibits breast
cancer proliferation in vitro.^10 And a team
led by Toshikazu Yoshikawa of Kyoto Pre-
fectural University determined that in a
mouse model of colon cancer, a myokine
known as secreted protein acidic and rich
in cysteine (SPARC) reduced tumorigene-
sis in the colon of exercising mice.^11 Over-
all, skeletal muscle cells may be secret-
ing several hundred myokine types, but
of these, only about 5 percent have been
investigated for their biological effects.
And researchers have tested fewer for
whether they regulate cancer cell growth.
Not all of the molecular messengers
released in response to exercise come fromSeveral myokines are
released only during
exercise, and some
researchers have
proposed that these
exercise-dependent
myokines contribute
to the myriad
beneficial effects of
physical activity for
all individuals, not
just cancer patients.