Anticancer Studies Of Koetjapic Acid Purified From Sandoricum Koetjape Merr
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Date
2011-02
Authors
Nassar, Zeyad D.
Journal Title
Journal ISSN
Volume Title
Publisher
Universiti Sains Malaysia
Abstract
Colorectal cancer which involves the colon, rectum and the anal canal is the third
most common malignancy worldwide. The disease is characterized by extensive
angiogenesis and perturbation of a variety of oncogenes and tumor suppressor genes
including, p53, Wnt, hypoxia, NF-кB, Notch, MAP kinase. Targeting one or more of
these pathways increases the selectivity of the chemotherapeutic agents as these
pathways are important for cancer cells growth and proliferation. Koetjapic acid is a
naturally occurring seco-A-ring oleanene triterpene present in the Sandoricum
koetjape species that grows in Malaysia and the Southeast Asian region. In this
study, a new method of koetjapic acid purification was developed to produce pure
koetjapic acid crystals at high yield. The structure of the compound was resolved and
confirmed using various physical and chemical methods which include: X-ray
crystallography, 1H NMR, IR, and mass spectra, and melting point determination.
The cytotoxic activity of koetjapic acid was assessed using MTT test against four
human cancer cell lines namely; colorectal carcinoma (HCT 116), hormone sensitive
breast cancer (MCF 7), hormone resistance breast cancer (MDA-MB-231) and liver
cancer (Hep G2) cell lines, in addition, two normal human cell line were tested;
colon (CCD-18Co) and umbilical vascular endothelial cells (HUVECs) . The results
showed that KA is a modest cytotoxic agent but exhibited selectivity against HCT
116 cell line with IC50 18.88 μg/ml. The cellular and molecular mechanisms of
anticancer activity of koetjapic acid towards human colorectal cancer were
investigated. Here we find that koetjapic acid induces apoptosis in HCT 116
colorectal cancer cells. The early changes accompanying the apoptosis process were
investigated by assessment of caspase activation. Koetjapic acid was found to cause
activation of downstream and upstream caspases.
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Keywords
Anticancer studies of koetjapic acid purified , from sandoricum koetjape merr