Biomaterial and Biomedicine, 2013, Vol.2, No.1, 1-5
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2
spectrum of tumour types in animal models (Rinehart
et al
.,
1999).
Early trial results have shown promising
activity of ET-743 in the treatment of advanced soft
tissue sarcoma (STS), osteosarcoma and metastatic
breast cancers. It was found that ET-743 prevents the
formation of P-glycoprotein, a protein associated with
multidrug-resistant tumours (Zewail-Foote et al., 1999).
Kahalalide F is a depsipeptide discovered in
Elysia
rufescens
,
a marine mollusc found in Hawaii. It caused
a disruption of lysosomal membranes and consequently
the formation of large vacuoles. This mechanism is
unique among anticancer agents and may cause
increasing acidification of the intra-cellular space, a
stimulatory event that initiates a pathway for apoptosis
(
Hamann et al., 1993). In addition, kahalaide F leads to
an inhibition of
erb
2
transmembrane tyrosine kinase
activity and inhibits TGF–a gene expression.
Discodermolide
is a polyhydroxylated lactone, isolated
from the deep-sea sponge
Discodermia
sp. It is an
immunosuppresive and cytotoxic agent (Gunasekera et
al., 1990). The study of its mechanism has revealed that
discodermolide was able to stabilise microtubules. In
1998,
Novartis Pharma AG
licensed this compound for
development as a candidate agent for treatment of
cancers.
Bryostatin 1
is a macrocyclic lactone isolated from the
marine bryozoan
Bugula neritina
(
Bugulidae). It has
many properties including activation of T-cells,
immunomodulation and stimulation of haematopoietic
progenitor cells. Bryostatin 1 was found to bind to
protein kinase C with high affinity, which may be the
mechanistic basis for both observed anticancer and
immunostimulating activities (De Vries et al., 1995).
Didemnin B is a depsipeptide isolated from the
Caribbean tunicate
Trididemnum solidum
.
It was found
to display antineoplastic, antiviral and subsequently
immunosuppresive activities (Rinehart et al., 1999).
Mechanistically, didemnin B acts at the GTP binding
protein elongation factor.
Ziconotide (Prialt) is a 25 amino acid peptide from the
venom of the predatory snail
Conus magnus
.
It acts by
binding to and inhibiting presynaptic calcium
channels, thereby preventing neurotransmitter release
(
Oliveira et al., 1985). It is licensed by Elan
Pharmaceuticals as Prialt. Prialt blocks nerve impulses
in a key region of the spinal cord, where pain fibres
from the body connect with the nerve cells that send
pain to the brain. This is why Prialt is 50 times more
potent than morphine.
In the present study an attempt has been made to
screen the cytotoxicity of marine sponge extracts of a
Aurora globostellata.
2.
Material and Methods
2.1
Sponge collection
Samples of
Aurora globostellata
were collected by
Scuba-divers at depths of 15 m (first collection) and 7
m (second collection), on Tuticorin Gulf of Mannar, in
the state of Tamilnadu. The sponge collection was
made in March - 2010 and these samples were directly
immersed in ethyl acetate. Samples from the second
collection, in May of 2011, were immediately frozen
under dry ice (-20
?
).
Both collections were sent to
Dept. of Zoology, Sri Paramakalyani College, and
Alwarkurichi. All samples were maintained at -20
?
,
and subsequently identified.
2.2.
Extract preparation
The sponge was extracted in ethyl acetate four times
by maceration in ethyl acetate (0.3 g/mL), over 4 days.
The ethyl acetate solution was reserved each of these
days. After the fourth day, the solutions were blended,
filtered, concentrated in a rotary evaporator and dried
in a Speed Vaccum evaporator. A portion of the
solution extracted from samples collected in 2011 was
partitioned against hexane (1:1, v/v) (100%), the lipid
portion was removed, and then the polar fraction was
dried in a SpeedVaccum evaporator. The sixteenth
fraction was tested for other activities
2.3.
Cell culture and cytotoxicity evaluation
The cell lines HeLa (Human cervical cancer), Raw
264.7 (
Mouse leukaemic monocyte macrophage cell
line) and HEK-293 (Human kidney cell line) were
obtained from American type culture collection
Manassas, VA, and cultured in Dulbecco's modified
Eagle's medium supplemented with 10% fetal bovine
serum (FBS), 2 mM glutamine and 100 µg/ml
Penicillin-Streptomycin incubated at 37
?
,
humidified