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Page 10 of 17 Gabriele et al. J Cancer Metastasis Treat 2018;4:17 I http://dx.doi.org/10.20517/2394-4722.2018.06

an increase in the expression of apoptotic proteins such as Bcl-2-associated X protein (Bax), cleaved poly
(ADP-ribose) polymerase (PARP), and cleaved caspase-3. Furthermore, it has been observed that Salen-Mn
induced expression of LC3-I/II in both dose- and time-dependent manner. It was documented that Salen-
Mn increased autophagy by means of AMPK phosphorylation. Therefore, Salen-Mn might represent a novel
promising candidate for the treatment of prostate cancer .
[129]

CONCLUDING REMARKS
Basal autophagy helps to maintain homeostasis by contributing to organelle and protein turnover, but
it is also a survival mechanism that is efficiently induced in stressed cells. Autophagy defects have been
implicated in various health states and diseases, including infection, myopathy, Crohn’s disease, neuro-
degeneration and cancer. However, the role of autophagy in cancer is quite complicated and still somewhat
controversial; it appears to be tumor suppressive during cancer development, but contributes to tumor cell
survival during cancer progression. Furthermore, tumor cells can use autophagy to resist to various anti-
cancer therapies. Cancer cells experience higher metabolic and energy demands and exposed to stresses
than normal cells because of their rapid proliferation and altered glycolytic metabolism. These cells depend
more heavily on autophagy for survival.

The therapeutic benefits of various cancer therapies have been improved because of the inhibition of autophagy,
which allows a methodology to specifically target cells characterized by higher levels of autophagy. There
is still much to be discovered about autophagy and its regulation, but the ongoing results are delineating
a promising pharmacological target for cancer treatment. However, it is necessary to discover additional
biomarkers to evaluate the complex dynamism of autophagy processes and to establish new methods to
assess autophagy in clinical samples.

The data here reviewed from the current scientific literature generally indicated that the modulation of
autophagy may be therapeutically beneficial in various tumors because of their ability to sensitize cancer
cells to the different therapies, including DNA-damaging agents, anti-hormone therapies and radiation and
chemotherapeutic combined strategies.

In particular, it is emerging that in prostate cancer, a promising combined treatment during androgen
deprivation therapy is to target metabolic stress-induced signaling pathways. These complex pathways
are intimately controlled by various molecular actors that play important roles in programmed cell death
pathways including autophagy and apoptosis. In particular, autophagy is clearly becoming a central regulator
of the main physiological and pathological processes, which through a precise and sensitive balancing
determine pro-death or pro-survival fate of the cell. Therefore, the modulation of autophagy process in
malignant cell types can be regarded as a potential strategy in cancer therapy.

DECLARATIONS
Authors’ contributions
Manuscript writing: Gabriele F, Martinelli C
Supervised the final version: Comincini S

Financial support and sponsorship
None.

Conflicts of interest
The authors declare that there is no conflict of interests regarding the publication of this paper.