Tannic acid ameliorates doxorubicin-induced cardiotoxicity and potentiates its anti-cancer activity: Potential role of tannins in cancer chemotherapy
Doxorubicin, an anthracycline antibiotic, is widely used in the treatment of various solid tumors including breast cancer. However, its use is limited due to a variety of toxicities including cardiotoxicity. The present study aimed to evaluate the effect of tannic acid, a PARG/PARP inhibitor and an antioxidant, on doxorubicin-induced cardiotoxicity in H9c2 embryonic rat heart myoblasts and its anti-cancer activity in MDA-MB-231 human breast cancer cells as well as in DMBA-induced mammary tumor animals. Doxorubicin-induced cardiotoxicity was assessed by measurement of heart weight, plasma LDH level and histopathology. Bcl-2, Bax, PARP-1 and p53 expression were examined by western blotting. Our results show that tannic acid prevents activation of PARP-1, reduces Bax and increases Bcl-2 expression in H9c2 cells, thus, preventing doxorubicin-induced cell death. Further, it reduces the cell viability of MDA-MB-231 breast cancer cells, increases p53 expression in mammary tumors and shows maximum tumor volume reduction, suggesting that tannic acid potentiates the anti-cancer activity of doxorubicin. To the best of our knowledge, this is the first report which shows that tannic acid ameliorates doxorubicin-induced cardiotoxicity and potentiates its anti-cancer activity both in vitro (H9c2 and MDA-MB-231 cells) as well as in in vivo model of DMBA-induced mammary tumor animals.
- OSTI ID:
- 21535253
- Journal Information:
- Toxicology and Applied Pharmacology, Vol. 251, Issue 3; Other Information: DOI: 10.1016/j.taap.2010.12.012; PII: S0041-008X(10)00469-2; Copyright (c) 2011 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; ISSN 0041-008X
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
ANTHRACENE
ANTIOXIDANTS
APOPTOSIS
CHEMOTHERAPY
DIMETHYLBENZANTHRACENE
DOXORUBICIN
HEART
HUMAN POPULATIONS
IN VITRO
IN VIVO
LACTATE DEHYDROGENASE
MAMMARY GLANDS
MYOBLASTS
NAD
NEOPLASMS
RATS
RIBOSE
TANNIC ACID
TOXICITY
ALDEHYDES
ANIMALS
ANTIBIOTICS
ANTI-INFECTIVE AGENTS
ANTINEOPLASTIC DRUGS
AROMATICS
BODY
CARBOHYDRATES
CARBOXYLIC ACIDS
CARDIOVASCULAR SYSTEM
COENZYMES
CONDENSED AROMATICS
DISEASES
DRUGS
ENZYMES
GLANDS
HEMIACETAL DEHYDROGENASES
HYDROCARBONS
HYDROXY COMPOUNDS
MAMMALS
MEDICINE
MONOSACCHARIDES
MUSCLES
NUCLEOTIDES
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
OXIDOREDUCTASES
PENTOSES
PHENOLS
POLYPHENOLS
POPULATIONS
PROTEINS
RODENTS
SACCHARIDES
THERAPY
VERTEBRATES