Exercise zaps cancer cells

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Exercise is a necessaty ingrediant in a healthy lifestyle, so don't skimp!

1}Studies shed new light on why exercise can protect against skin and

bowel cancers

Two studies published today (Saturday 13 May) have shown that exercise

can protect against skin and bowel cancer, and they have identified

new mechanisms that could be responsible for this effect.*

Published in the journal " Carcinogenesis " , one study found that female

mice that had 24-hour access to running wheels and were exposed to

ultraviolet B light (UVB) took longer to develop skin tumours,

developed fewer and smaller tumours, and had decreased amounts of body

fat compared to mice that did not have access to running wheels. The

second study looked at the development of pre-cancerous polyps in the

intestines of male mice and discovered that voluntary exercise and a

restricted diet reduced the number and size of polyps and improved

survival.

Dr Allan Conney, Garbe Professor of Cancer and Leukemia Research and

Director of the Lehman Cullman Laboratory for Cancer Research at

Rutgers University, New Jersey, USA, is one of the authors of the skin

cancer study. He said that programmed cell death (apoptosis),

triggered by exercise, might explain why the running wheel mice did

better.

" Preliminary indications from follow-up work in the laboratory suggest

that voluntary exercise enhances UVB-induced apoptosis in the skin,

and that it also enhances apoptosis in UVB-induced tumours. So,

although UVB is triggering the development of tumours, exercise is

counteracting the effect by stimulating the death of the developing

cancer cells.

" Our studies may be the first to suggest an apoptotic mechanism for

the effect of voluntary exercise in the development of cancer. In

addition, we found that voluntary exercise decreased body fat and that

the number of tumours decreased with decreasing amounts of fat. This

effect may also play an important role in the mechanism and warrants

further investigation, bearing in mind the growing rates of obesity in

the Western world, particularly in the USA and UK, " he said.

Dr Colbert, Assistant Professor at the University of

Wisconsin-Madison, USA, lead author of the bowel cancer study, said

that her study was the first to suggest that a negative energy

balance, produced by increasing the mice's energy output (by use of a

running wheel) while maintaining a restricted calorie intake, appeared

to be the important factor in inhibiting the growth of polyps (the

fore-runners of bowel tumours).

" Negative energy balance was indicated by a lower body weight among

the exercising mice, although they retained more body fat at the end

of the study than the non-exercising mice – an observation that might

be due to the fact that the exercising mice were healthier, while the

health of the non-exercising mice was beginning to decline due to

higher numbers of polyps. There were higher levels of hormones known

to be associated with the onset of cancer – insulin-like growth

factor-1 (IGF-1) and corticosterone – amongst the exercising mice, but

this did not correlate with higher total polyp numbers. These data

suggest that voluntary exercise that induces a negative energy balance

protects against the onset of cancer in these mice, but that the

mechanism is unlikely to be related to body composition, IGF-1 or

corticosterone. "

Dr Conney emphasised that it was not known yet whether exercise

decreased the risk of sunlight-induced skin cancer in humans, and

clinical trials were needed to investigate this further. However, in

bowel cancer, evidence from population studies already suggests that

physically active people have a reduced risk of developing the

disease, but the mechanisms remain unclear.

The skin cancer study involved two experiments. In a " high risk "

model, mice were exposed to UVB three times a week for 16 weeks, and

then for the subsequent 14 weeks, in the absence of further UVB

treatment, half the mice had access to running wheels in their cages

while the other half did not. In a second, " complete carcinogenesis "

model, mice were exposed to UVB twice a week for 33 weeks and, from

the beginning, half had access to a running wheel and half did not.

Mice not exposed to UVB acted as controls for the study. In both

models, the exercising mice increased their food intake and maintained

their normal body weight.

The exercising mice in the high risk model had an average of seven

weeks without tumours after the UVB exposure ceased, while the

non-exercising mice only had an average of 3.5 tumour-free weeks.

Dr Conney said: " In both the no running wheel and running wheel

groups, the number of tumours per mouse increased with time, but

throughout the 14 weeks of tumour development, animals with access to

running wheels had a decreased number of tumours per mouse compared to

animals with no running wheels. At all times, the tumour size in the

no running wheel group was greater than in the running wheel group; on

average, the tumour size per mouse for the no wheel group was just

over three times more than for the exercise group. "

In the complete carcinogenesis model, mice with no running wheel

started to develop tumours 20 weeks after the start of UVB exposure,

while tumours in the running wheel group started after 23 weeks. The

average tumour-free time was 25 weeks for the no running wheel group

and 27 weeks for the running wheel group.

Dr Conney said: " The rate of increase in tumour numbers per mouse for

the no running wheel group was significantly greater than that for the

running wheel group. On average, the tumour size per mouse for the no

running wheel group was about 3.5 times more than in the exercise group.

" In both models, voluntary running decreased the number of

non-malignant tumours per mouse by 34%. Exercise substantially

decreased the size of non-malignant tumours and malignant tumours: in

the high risk model, the non-malignant tumour size per mouse was

decreased by 54% and the malignant tumour size per mouse by 73%, and

in the complete carcinogenesis model, tumour size per mouse was

decreased by 75% and 69% respectively. "

For the bowel cancer study, Dr Colbert and her co-authors used mice

(APC Min mice) that had a genetic mutation that predisposed them to

develop intestinal polyps. " Our studies are relevant for humans in

that these Min mice have a mutation in one of the same genes, APC,

that is also mutated in human colon cancer, " she explained. " The

protective effect of exercise and lower body weight in our mice is

consistent with epidemiological evidence in humans that suggests

higher levels of activity and lower body weight reduces the risk of

colon cancer. "

Mutations in the APC gene in humans are responsible for an inherited

condition called familial adenomatous polyposis (FAP). FAP affects

about one in 10,000-15,000 people worldwide, 95% of whom will develop

numerous polyps in the bowel which eventually develop into colon

cancer, usually before the age of 40. The gene is mutated in sporadic

forms of colon cancer as well.

The researchers randomly assigned seven-week-old male mice to either

voluntary wheel running or to no exercise for 10 weeks. For the first

three weeks both groups had the same amount of food and water, but

after that the exercising mice were fed the amount that the

non-exercising mice had eaten the week before so that their food

consumption was unable to rise with their increased activity, thereby

producing a negative energy balance.

By the end of the ten weeks, six of the 23 control mice had died due

to the number of polyps that had grown and the resulting anaemia,

while all the 24 exercising mice were still alive.

" The exercising mice ran an average of 3.8 km a day, and the further

they ran the fewer polyps they had. Exercise significantly reduced

total polyp number and polyp size, as well as prolonging survival, "

said Dr Colbert. " On average there were 16 polyps per mouse in the

exercising mice compared to 22 polyps in the control mice – a decrease

of 25%. "

2)Inhibitory effects of voluntary running wheel exercise on

UVB-induced skin carcinogenesis in SKH-1 mice

Michna 1, C. Wagner 2, You-Rong Lou 3, Jian-Guo Xie 3,

Qing-Yun Peng 3, Yong Lin 4, Kirsten Carlson 2, Weichung Joe Shih 4,

Allan H. Conney 3, and Yao-Ping Lu 3 *

1 Joint Graduate Program in Toxicology, Rutgers, The State University

of New Jersey and The University of Medicine and Dentistry of New

Jersey- Wood Medical School, Piscataway, NJ, 08854

2 Department of Psychology, Rutgers, The State University of New

Jersey, Piscataway, NJ, 08854

3 Lehman Cullman Laboratory for Cancer Research, Department of

Chemical Biology, School of Pharmacy, Rutgers, The State University of

New Jersey, Piscataway, NJ, 08854

4 The Cancer Institute of New Jersey, New Brunswick, NJ, 08901

* To whom correspondence should be addressed.

Yao-Ping Lu, E-mail: sago@...

Abstract

Earlier studies showed that oral administration of green tea or

caffeine to SKH-1 mice inhibited UVB-induced skin carcinogenesis,

decreased dermal fat thickness and increased locomotor activity

(Michna et al., 2003). In the present study, the effects of voluntary

running wheel exercise on thickness of dermal fat as well as on

UVB-induced tumorigenesis in SKH-1 mice were studied in UVB-initiated

high-risk and UVB-induced complete carcinogenesis models. In the

high-risk model, animals were exposed to UVB (30 mJ/cm2) 3 times/week

for 16 weeks. For 14 weeks subsequent to UVB exposure, half of the

animals had access to running wheels in their cages while the other

half did not. In the complete carcinogenesis model, animals were

exposed to UVB (30 mJ/cm2) twice/week for 33 weeks. From the

beginning, half of the animals had access to running wheels while the

other half did not. At the conclusion of each study, body weights were

not different between groups, although animals with running wheels

consumed significantly more food and water than animals without

running wheels. In addition, animals with running wheels had decreases

in parametrial fat pad weight and thickness of the dermal fat layer.

In both UVB-initiated high-risk and complete carcinogenesis models,

voluntary running wheel exercise delayed the appearance of tumors,

decreased the number of tumors per mouse and decreased tumor volume

per mouse. Histopathology studies revealed that running wheel exercise

decreased the number of nonmalignant tumors (primarily

keratoacanthomas) by 34% and total tumors per mouse by 32% in both

models, and running wheel exercise decreased the formation of squamous

cell carcinomas in the UVB-induced complete carcinogenesis model by

27%. In addition, the size of keratoacanthomas and squamous cell

carcinomas were decreased substantially in both models. The effects

described here indicate that voluntary running wheel exercise inhibits

UVB-induced skin tumorigenesis and may also inhibit tumor growth.

(This study was supported in part by NIH Grants ES05022, CA80759 and

CA88961 as well as a State of New Jersey Commission on Cancer Research

Grant 05-1976-CCR-EO).

3)Negative energy balance induced by voluntary wheel running inhibits

polyp development in APCMin mice

H. Colbert 1 *, Volker Mai 2, Janet A. Tooze 3, N. Perkins

4, Berrigan 4, and D. Hursting 5

1 Department of Kinesiology and Comprehensive Cancer Center,

University of Wisconsin, Madison, WI

2 Department of Epidemiology and Preventive Medicine, University of

land, Baltimore, MD

3 Wake Forest University School of Medicine, Winston-Salem, NC

4 National Cancer Institute, Bethesda, MD

5 Department of Human Ecology, University of Texas, Austin, TX

* To whom correspondence should be addressed.

H. Colbert, E-mail: lhcolbert@...

Abstract

Treadmill running of ~0.9 km/day has had inconsistent effects on

spontaneous intestinal polyp development in C57BL/6J-ApcMin/J (Min)

mice; the amount of energy expenditure and/or a lack of hormonal

changes could account for this variability. The purpose of this study

was to examine the effects of a negative energy balance induced by

voluntary wheel running on polyps, insulin-like growth factor-1

(IGF-1), and corticosterone in Min mice. Seven-week-old male Min mice

were randomly assigned to control (CON, n=23) or wheel running (EX,

n=24) conditions for a 10-wk study period. All mice had water and

AIN-76A diet ad libitum for the first ~3 wks on study, after which the

EX group was pair-fed to the CON group to maintain a negative energy

balance due to the exercise. EX mice voluntarily ran 3.8 km/d (2.7 -

6.0 km/d) (median, interquartile range) and weighed less than CON mice

throughout the study. More CON mice died prior to the end of the study

vs. EX mice (26% vs. 0%, p<0.01). CON mice had significantly more

polyps vs. EX mice (21.6 ± 1.5 vs. 16.9 ± 2.0, p<0.01; mean ± SE), and

daily running distance in EX was inversely correlated with total polyp

number (r= -0.70, p<0.01). Urinary corticosterone output (p<0.01), and

serum IGF-1 were significantly higher in EX than CON (p<0.001);

however, total polyp number was unrelated to corticosterone (r=0.05,

p=0.84) and IGF-1 (r=-0.01, p=0.93). In this study, a negative energy

balance produced by wheel running exercise and restricted feeding

decreased polyp burden in male Min mice and appeared to have a

dose-response effect on polyp number. Although EX affected IGF-1 and

corticosterone, neither marker was related to total polyp number.

PS don't try speculate on this just do it