Probiotics in treatment of cancer

1. Navaira Arif
B.S. Biotechology
Institute of Biochemistry and
Biotechnology
University of The Punjab,
Lahore.

2. Breast cancer is when a cancerous tumor
occurs inside the breast
the most frequent invasive tumor
diagnosed in women, causing over
400,000 deaths yearly worldwide
One in 8 women will develop breast cancer
during her lifetime
the lowest incidence among Asians and
the highest among North Americans

3. Environment
Lifestyle
Medical Treatment
Genetics and Mutations
1. BRCA1 and BRCA2
2. P53

4.  First described in 1979
 First tumor suppressor gene to be identified
 Known as “Guardian of Genome”
 P53 signalling pathway remain in “standby”
mode in normal cellular functions
 Activation occurs in response to cellular
stresses
 involved in apoptosis since it protects
damaged DNA from being passed on

5. Oncogenic
stress
DNA
damage
Phosphoryltion
of serine 15
P21
transcriptional
upregulation
Cell cycle
arrest at G1
phase
Activation of
apoptotic
proteins (BAX)
Down-
regulation of
antiapoptotic
proteins
Induce
apoptosis

6. less frequently than in other solid tumours
About 20 to 35% of breast tumours are
due to mutant p53
Most are point missense mutations leading
to synthesis of malfunctioned protein
The most aggressive type of Breast
Cancer, Triple Negative Breast Cancer,
has more frequent p53 mutations

7. Most of p53 mutations are of somatic
origin
Sequence analysis of p53 revealed
mutations in N and C termini of proteins
 Missense mutation in codon 220
 Over-representation of TAC to TGC
alteration at codon 163
Accounts for 2% of all breast cancers

8.  localized in DNA binding domain (binding
site for ASPP1 and ASPP2)
ASPP1is no longer able to bind protein
Thus, providing anti-apoptotic actions

9.  A hereditary Li–Fraumeni syndrome is
associated with germ line Tp53 mutations.
 Of all tumors, this syndrome confers high risk
~25% for breast cancers
 This implies an important role for p53
inactivation in mammary carcinogenesis
 Mutations of BRCA1and BRCA2
 BRCA1, a scaffold for p53 response

10. A study on Southern Brazilian population
shows similarity of 65% mis-sense
mutations with somatic ones
Germline alteration occurs in codon 337

11. Study of expression of mutant p53 in
breast cancer cell lines
Ist case
• Loss of heterozygosity in p53 gene
along with mutated residual alleles
2nd Case
• Loss of heterozygosity in p53 gene
retain a wild type p53
• Almost 60% of breast cancers retain
wild type allele

12. Phosphorylation of p53 in response to γ-
irradiation occurs via ATM
ATM- the gene mutated in ataxia-
telangiectasia (A-T)
A-T patients have a high incidence of
breast cancer
Study showing heterozygosity for
truncating mutations in approximately one
in 50 patients

13. σ is a direct transcriptional target for p53
Analysis in primary breast carcinomas
shows the silencing of σ results in its down
regulation
Hence, loss of expression of p53 occurs.

14. MDM2 is antagonist of p53
Amplification of MDM2 causes p53
inactivation
Usually infrequent in breasts cancers.

15. Detection of tumor specific DNA in plasma
P53 mutations were found in the blood
The most adverse prognostic marker of
survival in breast cancer patients

16. P53 dysfunction leads to immuno
suppression
the production of inflammatory cytokines is
enhanced
shifts the balance between tolerance and
inflammation towards inflammation

17. Probiotics can suppress
the growth of Breast
Cancer due to their
immunomodulative
property

18. Greek word
Pro meaning "promoting,"
and biotic meaning "life."
Live microorganisms
Discovered in 20th
century by Elie
Metchnikoff, known as
the "father of probiotics“.

19. Modification of
gut microbiota
Strengthening of
the gut epithelial
barrier
Modulation of the
immune system

20. by contacting with the immune
components of the GI tract
by interacting with epithelial and dendritic
cells (DCs), monocytes/macrophages and
lymphocytes
by cytokine production and modification of
T-cell function

21. Different kinds of probiotics play
role in reduced breast tumor
growth by cytokine production
and anti tumoral cell activation

22. Cell wall components of
lactobacilli induce
activation of DCs
Produce
proinflammatory
cytokines
Actiavte natural killer
cells

23. Isolated from home made yogurt and neonatal
stool
Treatment of
L.acidophilus
with 4T1 tumor
bearing mice
Cytokine (IL-12)
production
increases
Production of
IFN-Y from T-
cells
Shift to Th1
pattern
Favor anti-tumor
activity

24.  Traditional probiotic
beverage
 fermentation of kefir grains
with milk or water
 Microbial flora includes
L.acidophilus,L.casei, and
Lactococcus lactis subsp
Lactis.
 Give anti-inflammatory,
immunomodulation, and
anticancer effects

25. Tumor Proliferation Immunomodulation Anti-angiogenesis
Cell cycle arrest at G1
Induction of apoptosis
Upregulation in
BAX-BCL ratio
Increase in p53-
independent p21
expression
CD4 and CD8
production
Cytokines IL-2
and IFN-Y
Anti-tumor
response
Down regulation of
IL-1B and VEGF

26. After 28 days of treatment, size and weight of tumors
in kefir water was reduced

27. Soy based products
Soymilk prevented the development of
mammary tumors
L. casei Shirota suppressed tumor growth
Inverse association of soy based products
with breast cancer incidence in Japanese
women
Enhanced NK activity

28. Fermented dairy products
Study in BALB/c mice
IL-10 cytokines
were increased
in mice fed with
fermented milk
Regulation of
immune
response in
mammary
glands

29. 4T1 breast cancer bearing mice were
given selenium nanoparticle-enriched L.
plantarum
elevation of the pro-inflammatory cytokines
IFN-γ, TNF-α and IL-2 levels
increased NK cell activity

30.  Somatic and germline p53 mutations are
observed in a significant minority of breast
cancers
 P53 dysfunction in tumor microenvironment
leads to immune suppression
 Breast microbiome and probiotic supplements
intake can play a major role in the
effectiveness of therapies for breast cancer
by improving health of immune system