Vol.:(0123456789) 1 3
Digestive Diseases and Sciences
https://doi.org/10.1007/s10620-018-4949-z
ORIGINAL ARTICLE
Chemoprevention by Probiotics During
1,2‑Dimethylhydrazine‑Induced Colon Carcinogenesis in Rats
Sohini Walia
1
· Rozy Kamal
2
· D. K. Dhawan
3
· S. S. Kanwar
1
Received: 3 January 2017 / Accepted: 23 January 2018
© Springer Science+Business Media, LLC, part of Springer Nature 2018
Abstract
Background Probiotics are believed to have properties that lower the risk of colon cancer. However, the mechanisms by
which they exert their benefcial efects are relatively unknown.
Aim To assess the impact of probiotics in preventing induction of colon carcinogenesis in rats.
Methods The rats were divided into six groups viz., normal control, Lactobacillus plantarum (AdF10)-treated, Lactobacil-
lus rhamnosus GG (LGG)-treated, 1,2-dimethylhydrazine (DMH)-treated, L. plantarum (AdF10) + DMH-treated and L.
rhamnosus GG (LGG) + DMH-treated. Both the probiotics were supplemented daily at a dose of 2 × 10
10
cells per day. DMH
at a dose of 30 mg/kg body weight was administered subcutaneously twice a week for the frst 4 weeks and then once every
week for a duration of 16 weeks. Glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione reductase
(GR), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and catalase as protein expression of genes involved
in apoptosis were assessed during DMH-induced colon carcinogenesis in rats.
Results DMH treatment decreased the activity of GSH, GPx, GST, SOD and catalase. However, AdF10 and LGG sup-
plementation to DMH-treated rats signifcantly increased the activity of these enzymes. Further, DMH treatment revealed
alterations in the protein expressions of various genes involved in the p53-mediated apoptotic pathway such as p53, p21,
Bcl-2, Bax, caspase-9 and caspase-3, which, however, were shifted towards normal control levels upon simultaneous sup-
plementation with probiotics.
Conclusion The present study suggests that probiotics can provide protection against oxidative stress and apoptotic-related
protein disregulation during experimentally induced colon carcinogenesis.
Keywords Probiotics · Colon cancer · Apoptosis · Oxidative stress · Animal model
Introduction
Colorectal cancer is the third most common type of malig-
nant disease worldwide with approximately 1 million
cases registered in 2008 [1]. Although chemotherapy and
radiotherapy are the available treatments for colon cancer,
their success rates vary with regard to local recurrence,
disease-free survival, and overall survival [2]. Therefore,
much attention has been focused on decreasing cancer risk
through diet management, particularly by increasing dietary
intake of probiotics. However, risk management by using
probiotics is another option which warrants consideration.
Probiotics are live microorganisms which benefcially afect
the host by improving its intestinal microbial balance [3].
There are a number of evidences to support the efcacy of
certain probiotic interventions in improving acute infectious
diarrhoea, antibiotic associated diarrhoea, irritable bowel
syndrome, pouchitis, ulcerative colitis and Crohn’s disease
[4, 5]. In addition, a possible role of lactic acid bacteria
(LAB) as a dietary supplement in the prevention of colon
cancer has received some attention. The diferent actions
which have been attributed to the anti-carcinogenic potential
of probiotic bacteria are binding and degradation of carcino-
gens, prevention of DNA damage, stimulation of protective
enzymes, augmentation in immune response, and production
* S. S. Kanwar
sskanwar1956@gmail.com
1
Department of Microbiology, CSK Himachal Pradesh
Agricultural University, Palampur, HP 176062, India
2
Centre for Nuclear Medicine, Panjab University,
Chandigarh 160014, India
3
Department of Biophysics, Panjab University,
Chandigarh 160014, India