200
effects. In traditional pharmaceutical approaches, drug delivery
systems were usually formulated using active anticancer drugs to
address clinical and pharmacological issues related to anticancer
drug properties, without changes in the fundamental pharmacokinetic properties of the active pharmaceutical ingredient, while the
major pharmaceutical challenges associated with newly discovered
potent anticancer drugs were poor aqueous solubility, cellular permeability, and low cellular drug bioavailability [6, 7].
Sphingolipids are substantial elements of human cell membranes. Currently, more than 300 sphingolipids (SPL) have been
detected. Sphingolipid metabolites, in particular, ceramide,
ceramide-1-phosphate (C1P), and sphingosine-1-phosphate (S1P),
are lipid agents which play the role of controlling sets of cellular
functions; this later contains cell growth, survival, migration,
immune cell trafficking, angiogenesis, apoptosis, autophagy, and
cancer [8, 9]. As a matter of fact, the generation of ceramide and
sphingosine is induced by chemotherapy, radiation, and/or oxidative stress, and these sphingolipids mediate cell death, senescence,
and/or cell cycle arrest. Nevertheless, metabolic conversion of
sphingosine-1-phosphate (S1P) to ceramide (Cer), sphingomyelin,
or glucosylceramide has anti-apoptotic and pro-survival roles [10].
Sphingolipids (SPL) are ubiquitous molecules essential for the
maintenance and development of living organisms. They are not
evenly distributed along the membrane but grouped as lipid microdomains called rafts. It has been thought for a long time that SPLs
have only a structural role. However, now it has been known that
they are playing a role in receptors and second messengers involved
in major functions of the cellular life and many genetic diseases
(sphingolipidoses) which are explained as a dysfunction of their
metabolism [11].
Recently, the outcomes of various studies have shown the
importance of total cell sphingosine lipids (in the phosphorylated
form) which play an essential role in cell death or cell survival message [12]. These studies have showed that different pathways of
the apoptosis occurrence, involving the internal, external, and
common pathway, will be quickly activated and the cell will soon
be directed to the planned death if this balance changes in any way
toward increasing total cellular ceramide [13]. On the contrary,
the segmentation of ceramides in the cytoplasm by increasing the
activity of diverse isoforms of ceramidase enzymes leads to a rise in
the levels of intracellular sphingosine [14]. Sphingosine, by mediating environmental evolution factors and excitant cytokines of
proliferation and division, is exposed to the action of the
sphingosine- 1-kinase. The phosphorylated sphingosine (through
the GPCR receptor) directly and indirectly catalyzes the contributory factors in cell division, such as PI3K and PLC [15]. It has
been shown that TNF stimulates apoptosis in tumor cells by raising
the output of ceramide; thus, ceramide does not need p53 [16].
Ali Ben Taleb et al.
effects. In traditional pharmaceutical approaches, drug delivery
systems were usually formulated using active anticancer drugs to
address clinical and pharmacological issues related to anticancer
drug properties, without changes in the fundamental pharmacokinetic properties of the active pharmaceutical ingredient, while the
major pharmaceutical challenges associated with newly discovered
potent anticancer drugs were poor aqueous solubility, cellular permeability, and low cellular drug bioavailability [6, 7].
Sphingolipids are substantial elements of human cell membranes. Currently, more than 300 sphingolipids (SPL) have been
detected. Sphingolipid metabolites, in particular, ceramide,
ceramide-1-phosphate (C1P), and sphingosine-1-phosphate (S1P),
are lipid agents which play the role of controlling sets of cellular
functions; this later contains cell growth, survival, migration,
immune cell trafficking, angiogenesis, apoptosis, autophagy, and
cancer [8, 9]. As a matter of fact, the generation of ceramide and
sphingosine is induced by chemotherapy, radiation, and/or oxidative stress, and these sphingolipids mediate cell death, senescence,
and/or cell cycle arrest. Nevertheless, metabolic conversion of
sphingosine-1-phosphate (S1P) to ceramide (Cer), sphingomyelin,
or glucosylceramide has anti-apoptotic and pro-survival roles [10].
Sphingolipids (SPL) are ubiquitous molecules essential for the
maintenance and development of living organisms. They are not
evenly distributed along the membrane but grouped as lipid microdomains called rafts. It has been thought for a long time that SPLs
have only a structural role. However, now it has been known that
they are playing a role in receptors and second messengers involved
in major functions of the cellular life and many genetic diseases
(sphingolipidoses) which are explained as a dysfunction of their
metabolism [11].
Recently, the outcomes of various studies have shown the
importance of total cell sphingosine lipids (in the phosphorylated
form) which play an essential role in cell death or cell survival message [12]. These studies have showed that different pathways of
the apoptosis occurrence, involving the internal, external, and
common pathway, will be quickly activated and the cell will soon
be directed to the planned death if this balance changes in any way
toward increasing total cellular ceramide [13]. On the contrary,
the segmentation of ceramides in the cytoplasm by increasing the
activity of diverse isoforms of ceramidase enzymes leads to a rise in
the levels of intracellular sphingosine [14]. Sphingosine, by mediating environmental evolution factors and excitant cytokines of
proliferation and division, is exposed to the action of the
sphingosine- 1-kinase. The phosphorylated sphingosine (through
the GPCR receptor) directly and indirectly catalyzes the contributory factors in cell division, such as PI3K and PLC [15]. It has
been shown that TNF stimulates apoptosis in tumor cells by raising
the output of ceramide; thus, ceramide does not need p53 [16].
Ali Ben Taleb et al.