Annona muricata leaves induce G₁ cell cycle arrest and apoptosis through mitochondria-mediated pathway in human HCT-116 and HT-29 colon cancer cells.

Article about Soursop

Reference

View article Open link

Abstract

  1. J Ethnopharmacol. 2014 Oct 28;156:277-89. doi: 10.1016/j.jep.2014.08.011. Epub
    2014 Sep 4.

Annona muricata leaves induce G₁ cell cycle arrest and apoptosis through
mitochondria-mediated pathway in human HCT-116 and HT-29 colon cancer cells.

Zorofchian Moghadamtousi S(1), Karimian H(2), Rouhollahi E(3), Paydar M(3),
Fadaeinasab M(4), Abdul Kadir H(5).

Author information:
(1)Biomolecular Research Group, Biochemistry Program, Institute of Biological
Sciences, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia.
(2)Department of Pharmacy, Faculty of Medicine, University of Malaya, 50603 Kuala
Lumpur, Malaysia.
(3)Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603
Kuala Lumpur, Malaysia.
(4)Department of Chemistry, Faculty of Science, University of Malaya, Kuala
Lumpur 50603, Malaysia.
(5)Biomolecular Research Group, Biochemistry Program, Institute of Biological
Sciences, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia.
Electronic address: [email protected]

ETHNOPHARMACOLOGICAL RELEVANCE: Annona muricata known as "the cancer killer" has
been widely used in the traditional medicine for the treatment of cancer and
tumors. The purpose of this study is to investigate the anticancer properties of
ethyl acetate extract of Annona muricata leaves (EEAM) on HT-29 and HCT-116 colon
cancer cells and the underlying mechanisms.
MATERIALS AND METHODS: The effect of EEAM on the cell proliferation of HT-29 and
HCT-116 cells was analyzed by the MTT
(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium) assay. High content
screening system (HCS) was applied to investigate the cell membrane permeability,
mitochondrial membrane potential (MMP), nuclear condensation and cytochrome c
translocation from mitochondria to cytosol. Reactive oxygen species (ROS)
formation, lactate dehydrogenase (LDH) release and activation of caspase-3/7, -8
and -9 were measured while treatment. Flow cytometric analysis was used to
determine the cell cycle distribution and phosphatidylserine externalization. The
protein expression of Bax and Bcl-2 was determined using immunofluorescence
analysis. In addition, the potential of EEAM to suppress the migration and
invasion of colon cancer cells was also examined.
RESULTS: EEAM exerted significant cytotoxic effects on HCT-116 and HT-29 cells as
determined by MTT and LDH assays. After 24 h treatment, EEAM exhibited the IC₅₀
value of 11.43 ± 1.87 µg/ml and 8.98 ± 1.24 µg/ml against HT-29 and HCT-116
cells, respectively. Flow cytometric analysis demonstrated the cell cycle arrest
at G1 phase and phosphatidylserine externalization confirming the induction of
apoptosis. EEAM treatment caused excessive accumulation of ROS followed by
disruption of MMP, cytochrome c leakage and activation of the initiator and
executioner caspases in both colon cancer cells. Immunofluorescence analysis
depicted the up-regulation of Bax and down-regulation of Bcl-2 proteins while
treated with EEAM. Furthermore, EEAM conspicuously blocked the migration and
invasion of HT-29 and HCT-116 cells.
CONCLUSIONS: These findings provide a scientific basis for the use of A. muricata
leaves in the treatment of cancer, although further in vivo studies are still
required.

Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

DOI: 10.1016/j.jep.2014.08.011
PMID: 25195082 [Indexed for MEDLINE]