hepatitis B, while HepG2 cells do not. Generally, HepG2 cells are
highly susceptible to chemical agents and drugs, while Hep3B cells
are more resistant because ofp53 deficiency [96]. As can be seen
(Table3), the cell line Hep3B shows a much greater value for the
entropy production rate compared to a HepG2.
The cell line PC3, which is known to have an increased invasive
ability and is more aggressive as compared to the LNCaP [97, 98],
shows a much greater value for the entropy production rate com-
pared to a LNCaP. These results corroborate, from the new point of
view of thermodynamics, what other studies have shown for the cell
line PC3, that is, it is more malignant, aggressive and has a higher
metastatic potential and is more resistant to treatment compared to
LNCaP [99]. It was found that the cellular line PC3 exhibits a
greater value of the entropy production rate compared to LNCaP.
As a fact, a similar result was found by us in previous work [49].
These results show how the entropy production rate can be a
useful tool to quantify the robustness and it may be used as a
quantitative index of the metastatic potential of tumors. (As can
be seen, this analysis suggests that the tumor cell lines that exhibit a
greater value of the entropy production rate have an increased
invasive ability and so they have more aggressive capacity. As a
matter of fact, the entropy production rate can be the useful tool
to quantify the robustness and it may be used as a quantitative index
of the metastatic potential of tumors.)4.1 The Influence
of Hypoxia, Normoxia,
and pH in Tumor Cells
The metabolism of cancer as a therapeutic target is under constant
investigation, along with the search for small molecules that are
capable of specifically inhibiting the key metabolic pathways asso-
ciated with cell growth [100]. Attenuation or inhibition of glycoly-
sis has been very helpful in preventing cancer development,
demonstrating that glycolysis is essential for proliferation, invasion,
and metastasis [100, 101]. Identification of the most important
reactions involved in the regulation of the glycolytic pathway is a
useful strategy to define therapeutic targets in oncology, and thus
can be a crucial step in cancer drug development. In addition,
research on the influence of intracellular pH in the robustness of
the glycolytic mechanism in neoplasic cells is equally important to
understand the cancer biology.
In previous studies we showed the way entropy production per
time can be used to select the main steps in a complex chemical
reactions network, as Belousov-Zhabotinsky reaction [102]. More-
over, we also showed that entropy production is a specific finger-
print of the behavior of tumor, related to cancer robustness and
prognostic of the disease [28]. The entropy production per time
unitS_iwithT,pfixed, disregarding diffusive and viscous effects of
each reaction of the glycolytic pathway, was assessed in [17]as
Eq. (4).148 Sheyla Montero et al.