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are thermolabile, and therefore cooked forms of cruciferous vegetables provide considerably less PEITC
[13]
to the body than raw forms . Recent studies of PEITC have focused on the phytochemical’s possible
role in cancer chemoprevention. Specifically, prostate cancer prevention has received attention, owing to
its long latency and because dietary exposure to PEITC is noninvasive and rather promising. Androgen
[14]
receptor signaling plays a significant role in many aspects of prostate cancer cell growth , suggesting the
utility of androgen responsive LNCaP cells, which are commonly used in many different prostate cancer
[15]
studies . The mitochondria’s role in metabolism makes it a major source of cellular energy. Therefore,
inhibiting mitochondrial function also depletes the available cellular energy, forcing the cells to destroy
[16]
themselves and use their contents for energy . Studies explored the mitochondrial structural alterations
and formation of autophagosomes upon treatment with PEITC in prostate cancer cells [17,18] . PEITC-induced
autophagyalong with apoptosis, contributing to growth suppression of prostate cancer cells both in cell
culture and in a transgenic mouse model of prostate cancer [19,20] .

Glycolysis refers to the aerobic or anaerobic catabolism of glucose, which results in pyruvate, NADH,
and ATP. Certain metabolic intermediates of glycolysis can also benefit cancer cells, as they promote
macromolecular biosynthesis, which enhances the available nutrient supply . Without the products of
[21]
glycolysis, cancer cells utilize the autophagic response, where they degrade cytosolic organelles to generate
energyfor survival . The effect of PEITC on glycolysis, miRNA, and the matrix metalloprotease (MMP),
[22]
MMP2/MMP9 signaling pathway was shown to slow the spread of prostate cancer. This study further
explored how PEITC could affect c-Myc-regulated glycolysis. PEITC exposure increased the level of c-Myc
proteins, known to inhibit the expression of the enzymeshexokinase 2 (HKII), pyruvate kinase isozyme 2
[23]
(PKM2), and lactate dehydrogenase A (LDHA), whichpromote glycolysis . PEITC exposure was shown
to inhibit glycolysis, as revealed by suppressed expression of important markers including HKII, PKM2,
[23]
and LDHA in LNCaP and 22Rv1 cells . This is a revolutionary finding, as PEITC-mediated inhibition of
glycolysis in cancer cells would eliminate a major energy store for prostate cancer cells, allowing for a new
type of chemotherapy, utilizing the cell’s natural autophagic response system. In addition, by inhibiting
glycolysis in cancer cells, PEITC has the potential to eliminate the common problem of multidrug-resistant
(MDR) hypoxia [24,25] , which is a major complication for other chemopreventive treatments. Hypoxia, a
known factor that transforms cancer cells into MDR cancer cells, also promotes cellular glycolysis through
what is known as the Pasteur effect. Hypoxia does this by manipulating cancer cells’ metabolism, resulting
[25]
in the induction of cellular quiescence . Therefore, hypoxia is a major cause of chemotherapeutic drug
resistance. Thus, PEITC’s role in inhibiting glycolysis in cancer cells may limit the hypoxic environment
and minimize the transformation of MDR cancer cells.

PEITC was also shown to induce autophagic response through the regulation of MMP2/MMP9 signaling
pathways. Both MMP2 and MMP9 proteins are responsible for extracellular matrix collagen/protein
degradation. Activation of MMP proteins can promote angiogenesis and limit cellular apoptosis, allowing
cancers to proliferate [26,27] . MMP2, MMP9, and c-myc work together in cancer progression. PEITC
was shown to downregulate the expression of MMP2, MMP9and c-myc proteins and simultaneously
[26]
induceautophagy . A study using hepatoma-derived growth factor resulted in tumor growth inhibition,
and proved a linkage between autophagy and MMP2, MMP9, and c-myc proteins. It also proved that by
modulating the signal pathway of the MMP2 and MMP9 proteins, prostate cancer cell migration and
[28]
invasion could be inhibited . MMP2 is also a downstream effector of the JAK/STAT pathway, involved in
tumorigenesis and metastasis. PEITC was shown to suppress the JAK/STAT-MMP2 pathway and induce
autophagy in vitroand in a lung cancer mouse xenograftmodel. However, autophagy induced by PEITC
[29]
preserved metastasis potential, which was abrogated in the presence of chloroquine . A different study
that explored PEITC’s epigenetic regulatory effects on miRNA in prostate cancer cells found that PEITC
influenced miR-194 levels and downregulated the expression of oncogenic MMP2 and MMP9 proteins.
[30]
The downregulation of MMP2 and MMP9 proteins ultimately reduced prostate cancer metastasis . It has