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J Biomed Sci. 2016 Apr 16;23:40. doi: 10.1186/s12929-016-0257-0.

Cytotoxicity and cell cycle arrest induced by andrographolide lead to programmed cell death of MDA-MB-231 breast cancer cell line.

Author information

1
Department of Microbiology, University of Kalyani, Kalyani, 741235, WB, India.
2
TCG Life Science Ltd., Bengal Intelligent Park, Tower-B, Block-EP & GP, Sector-5, Salt Lake, Kolkata, 700091, India.
3
Department of Biotechnology, Visva-Bharati, Santiniketan, 731235, India.
4
Department of Microbiology, University of Kalyani, Kalyani, 741235, WB, India. dr.samirmukherjee@gmail.com.

Abstract

BACKGROUND:

Breast cancer is considered as an increasing major life-threatening concern among the malignancies encountered globally in females. Traditional therapy is far from satisfactory due to drug resistance and various side effects, thus a search for complementary/alternative medicines from natural sources with lesser side effects is being emphasized. Andrographis paniculata, an oriental, traditional medicinal herb commonly available in Asian countries, has a long history of treating a variety of diseases, such as respiratory infection, fever, bacterial dysentery, diarrhea, inflammation etc. Extracts of this plant showed a wide spectrum of therapeutic effects, such as anti-bacterial, anti-malarial, anti-viral and anti-carcinogenic properties. Andrographolide, a diterpenoid lactone, is the major active component of this plant. This study reports on andrographolide induced apoptosis and its possible mechanism in highly proliferative, invasive breast cancer cells, MDA-MB-231 lacking a functional p53 and estrogen receptor (ER). Furthermore, the pharmacokinetic properties of andrographolide have also been studied in mice following intravenous and oral administration.

RESULTS:

Andrographolide showed a time- and concentration- dependent inhibitory effect on MDA-MB-231 breast cancer cell proliferation, but the treatment did not affect normal breast epithelial cells, MCF-10A (>80 %). The number of cells in S as well as G2/M phase was increased after 36 h of treatment. Elevated reactive oxygen species (ROS) production with concomitant decrease in Mitochondrial Membrane Potential (MMP) and externalization of phosphatidyl serine were observed. Flow cytometry with Annexin V revealed that the population of apoptotic cells increased with prolonged exposure to andrographolide. Activation of caspase-3 and caspase-9 were also noted. Bax and Apaf-1 expression were notably increased with decreased Bcl-2 and Bcl-xL expression in andrographolide-treated cells. Pharmacokinetic study with andrographolide showed the bioavailability of 9.27 ± 1.69 % with a Cmax, of 0.73 ± 0.17 μmol/L and Tmax of 0.42 ± 0.14 h following oral administration. AG showed rapid clearance and moderate terminal half lives (T1/2) of 1.86 ± 0.21 and 3.30 ± 0.35 h following IV and oral administration respectively.

CONCLUSION:

This investigation indicates that andrographolide might be useful as a possible chemopreventive/chemotherapeutic agent for human breast cancers.

KEYWORDS:

Andrographolide; Apoptosis; Bioanalysis; Breast cancer; Cell cycle arrest; Phytomedicine

PMID:
27084510
PMCID:
PMC4833932
DOI:
10.1186/s12929-016-0257-0
[Indexed for MEDLINE]
Free PMC Article

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