83
Neovastat were serious setbacks to its use in cancer treatment” (Patra and Sandell
2012 ). Thus, it was reported that sharks shown symptoms of both malignant and
benign neoplasms. According to Finkelstein ( 2005 ), because of absence of really
existing antiangiogenic and anti-invasive substances in cartilage, there is no logic
for additional justifi cations for using shark cartilage. The fact that some people
believe shark cartilage consumption can cure cancer seems to be an example of
pseudoscience. Moreover, such negative outcomes as a diversion of patients from
effective cancer treatments as well as increased decline in shark populations have
been registered (Ostrander et al. 2004 ).
However, other authors reported about suppression of carcinogenesis (Sato et al.
2004 , 2008 ), growth of tumor, as well as angiogenesis in animal models (see for
review Kitahashi et al. 2012 ) by oral administration of shark cartilage. Especially,
low molecular weight proteins (smaller than 20 kDa) have been suggested to be
involved in the benefi cial effects by oral administration of shark-cartilage-based
products (Bargahi and Rabbani–Chadegani 2008 ; Kitahashi et al. 2012 ). These low
molecular weight substances exerting antiangiogenesis, immunostimulation, and
MMP-9 inhibitory activities. Additional “positive” example is the squalamine
(Moore et al. 1993 ; Li et al. 2002 ), which is isolated from liver and stomach of the
dogfi sh shark ( Squalus acanthias ). This aminosterol inhibited solid tumor growth
and angiogenesis in vivo (Sills et al. 1998 ).
The next example, Neovastat, is a naturally occurring multifunctional antiangiogenic drug (Falardeau et al. 2001 ). Neovastat (or AE-941) contains a mix of watersoluble components less than approximately 500 kDa derived after homogenisation
of the shark cartilage in water followed by sequential extraction to remove inactive
and water-insoluble molecules. The drug is prepared by a proprietary manufacturing process developed by Aeterna Laboratories (Quebec, Canada) (Dupont et al.
1997 ). The effects observed after Neovastat treatments are listed by Patra and
Sandell ( 2012 ) as follow:
– “it induced a concentration-dependent inhibition of cell proliferation in human
umbilical vein endothelial cells (HUVECs) and bovine endothelial cells;
– it inhibited the formation of blood vessels induced by basic fi broblast growth
factor (FGF) in the chicken chorioallantoic membrane model;
– it severely inhibited in vivo the vascular invasion of bFGF-containing Matrigel
implanted in C57BL6 mice fed orally with Neovastat;
– it inhibited lung metastases in the murine Lewis lung carcinoma model,” (Patra
and Sandell 2012 ).
In addition, Neovastat shown synergetic effect being combined with, a conventional anticancer agent named cisplatin . It exhibited greater anticancer activity than
cisplatin alone (Patra and Sandell 2012 ).
Studies involving the isolation of novel functional biomolecules from shark cartilage are still on-going. For example, as recently reported by O’Connell et al.
( 2012 ), Trimethylamine N-oxide (TMAO), extracted from shark cartilage is a kind
of a natural osmolyte, that induce protein folding, and counteracts the destabilizing
effect of the high concentrations of urea stored by the fi sh.
2.1 From Non-mineralized to Mineralized Cartilage
Neovastat were serious setbacks to its use in cancer treatment” (Patra and Sandell
2012 ). Thus, it was reported that sharks shown symptoms of both malignant and
benign neoplasms. According to Finkelstein ( 2005 ), because of absence of really
existing antiangiogenic and anti-invasive substances in cartilage, there is no logic
for additional justifi cations for using shark cartilage. The fact that some people
believe shark cartilage consumption can cure cancer seems to be an example of
pseudoscience. Moreover, such negative outcomes as a diversion of patients from
effective cancer treatments as well as increased decline in shark populations have
been registered (Ostrander et al. 2004 ).
However, other authors reported about suppression of carcinogenesis (Sato et al.
2004 , 2008 ), growth of tumor, as well as angiogenesis in animal models (see for
review Kitahashi et al. 2012 ) by oral administration of shark cartilage. Especially,
low molecular weight proteins (smaller than 20 kDa) have been suggested to be
involved in the benefi cial effects by oral administration of shark-cartilage-based
products (Bargahi and Rabbani–Chadegani 2008 ; Kitahashi et al. 2012 ). These low
molecular weight substances exerting antiangiogenesis, immunostimulation, and
MMP-9 inhibitory activities. Additional “positive” example is the squalamine
(Moore et al. 1993 ; Li et al. 2002 ), which is isolated from liver and stomach of the
dogfi sh shark ( Squalus acanthias ). This aminosterol inhibited solid tumor growth
and angiogenesis in vivo (Sills et al. 1998 ).
The next example, Neovastat, is a naturally occurring multifunctional antiangiogenic drug (Falardeau et al. 2001 ). Neovastat (or AE-941) contains a mix of watersoluble components less than approximately 500 kDa derived after homogenisation
of the shark cartilage in water followed by sequential extraction to remove inactive
and water-insoluble molecules. The drug is prepared by a proprietary manufacturing process developed by Aeterna Laboratories (Quebec, Canada) (Dupont et al.
1997 ). The effects observed after Neovastat treatments are listed by Patra and
Sandell ( 2012 ) as follow:
– “it induced a concentration-dependent inhibition of cell proliferation in human
umbilical vein endothelial cells (HUVECs) and bovine endothelial cells;
– it inhibited the formation of blood vessels induced by basic fi broblast growth
factor (FGF) in the chicken chorioallantoic membrane model;
– it severely inhibited in vivo the vascular invasion of bFGF-containing Matrigel
implanted in C57BL6 mice fed orally with Neovastat;
– it inhibited lung metastases in the murine Lewis lung carcinoma model,” (Patra
and Sandell 2012 ).
In addition, Neovastat shown synergetic effect being combined with, a conventional anticancer agent named cisplatin . It exhibited greater anticancer activity than
cisplatin alone (Patra and Sandell 2012 ).
Studies involving the isolation of novel functional biomolecules from shark cartilage are still on-going. For example, as recently reported by O’Connell et al.
( 2012 ), Trimethylamine N-oxide (TMAO), extracted from shark cartilage is a kind
of a natural osmolyte, that induce protein folding, and counteracts the destabilizing
effect of the high concentrations of urea stored by the fi sh.
2.1 From Non-mineralized to Mineralized Cartilage