Sen S, Kawahara B, Chaudhuri G.Free Radic Biol Med. 2012 Oct 15;53(8):1541-51. doi: 10.1016/j.freeradbiomed.2012.06.030. Epub 2012 Jun 27.

Breast Cancer and Antioxidants: The Mechanism of Cancer Progression

Sen S, Kawahara B, Chaudhuri G.Free Radic Biol Med. 2013 Apr;57:210-20. doi: 10.1016/j.freeradbiomed.2012.10.545. Epub 2012 Oct 23.

Department of Obstetrics and Gynecology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA

GAUTAM CHAUDHURI

Production of Hydrogen Peroxide in Human Breast Cancer Cells: Comparisonwith Normal Human Breast Cells

Protein Expression /Specific Activity of Catalase in Human Breast Cancer Cells : Comparison with Normal Human Breast cells

MW

Catalase, 65 kDa →GAPDH, 36 kDa →

b

Production of Superoxide and its Correlation to the Specific Activity of Catalase:

Silencing of Catalase Induces Growth of Human Breast Cancer Cells

Decrease in Protein phosphatase 2A ( PP2A) Activity upon Silencing of Catalase:Activity of PP2A is Dependent on the Redox State of its Thiols.

MDA-MB-468

PP2A Activity was Inhibited by H2O2 but Induced by α-Tocopherol (A superoxideQuencher)

Catalase Superoxide H2O2αTocopherol

PP2AReduced Growth

0

50

100

150

200

250

e

****

** *

MDA-MB-468

Okadaic Acid

Pro

life

ra

tio

n (

%

Co

ntr

ol)

Inhibition of PP2A Activity Lead to Proliferation of Human Breast Cancer cells:

Catalase,65kDa

GAPDH,36kDa

a

Overexpression of Catalase Lead to a Reduction in H2O2 Levels Accompanied by a Reduction in Cell Viability

f

Annexin V-Cy3

MDAempty

MDAoxCAT

7-A

AD

43.6 18.8%

9.5 1.5%

GAPDH, 36 kDa

pAKT, 65kDa

BAX, 20kDa

Total AKT, 65kDa

i

Overexpression of Catalase Lead to Apoptosis in Human Breast Cancer cells

7-A

AD

Annexin V-Cy3

MCF-7empty MCF-7oxCAT9.2 2.3% 51.8 5.5%

HMECempty HMECoxCAT7.4 0.3% 7.9 1.4%

a

Overexpression of Catalase did not Induce Apoptosis in Normal Human Breast Cells

GAPDH, 36 kDa

Catalase, 65 kDa

b

0.0

100.0

200.0

300.0

400.0

500.0

Normal Tissue Tumor Tissue

a

Spe

cifi

c C

atal

ase

Act

ivit

y(L

um

/mO

D @

600

nm

)

Human Breast Cancer Tissues Exhibited Higher Catalase expression but LowerSpecific Activity when Compared to Normal Breast Tissues.

• J Natl Cancer Inst. 1993 Sep 15;85(18):1483-92.• Nutrition intervention trials in Linxian, China: supplementation with specific vitamin/mineral

combinations, cancer incidence, and disease-specific mortality in the general population.

The findings indicate that vitamin and mineral supplementation of the diet of Linxian adults, particularly with the combination of beta carotene, vitamin E, and selenium, may effect a reduction in cancer risk in this

population.

Ther Adv Med Oncol. 2014 Mar;6(2):52-68.Anti-inflammatory/antioxidant use in long-term maintenance cancer therapy: a new therapeutic

approach to disease progression and recurrence.

The high-activity catalase CC genotype was associated with an overall 17% reduction in risk of breast cancer compared with having at least one variant T allele (odds ratio = 0.83, 95% confidence interval: 0.69, 1.00). Vegetable and, particularly, fruit consumption contributed to the decreased risk associated with the catalase CC genotype. 

Biochem Pharmacol. 2011 Nov 15;82(10):1384-90. doi: 10.1016/j.bcp.2011.06.007. Epub 2011 Jun 13.Catalase overexpression in mammary cancer cells leads to a less aggressive phenotype and an altered response to chemotherapy.

Antioxidants associated with decreased risks of Breast Cancer

Endogenous Production Of Nitric Oxide Induces Growth in Human Breast CancerCells (ZR-75-30 & BT-474): ( Cross Talk with H2O2)

ZR-75-30

Endogenous Production Of Nitric Oxide Induces Growth in Human Breast CancerCells (ZR-75-30 & BT-474): ( Cross Talk with H2O2)

Endogenous Production Of Nitric Oxide Does Not Induce Growth in Normal Human Breast Cells (ZR-75-30 & BT-474)

Nitric Oxide Synthase Activity Present in Mitochondrial Fractions from Cancer cells

b

DCFDA (FL1-H)

Cel

l Cou

nt ← L-NAME, 5mM

← Control

Mitosox (FL2-H)

L-NAME, 5mM

Control

Cel

l Cou

nt

←

→

c

Inhibition of Nitric Oxide Formation Lowers Superoxide as well as Hydrogen Peroxide Production

Nitric Oxide (Produced Endogenously)

Cytochrome c oxidaseInhibits

[O2.- ][H2O2 ]Inhibits

PP2AIncreases

pERK/ERK

pAKT/AKT

Increased Growth

Catalase

Human Breast Cells

Summary