22.22 KV Channel as Therapeutic Target for Prostate
Cancer Treatment
The concept of KV channel as therapeutic target for prostate cancer treatment attracts
increasing interest, but the lack of effective and selective KV channel modulators has
hindered the progression of treatment strategy (Schönherr 2005). Exploring the
functional properties of ion channels in cancer progression and metastatic behavior
is emerging as a novel approach for the development of effective anticancer treatment. Potassium (K+) channels in the plasma membrane of tumor cells contribute to
a wide range of cellular processes including cell cycle progression, cell proliferation,
and apoptosis (Ouadid-Ahidouch and Ahidouch 2008). In particular, K+ channels
play a crucial role in cell proliferation, as its activation is a prime factor for cell cycle
progression through early G1 phase of the cell cycle (Wonderlin and Strobl 1996).
Hence, the blockage of K+ channel activity has shown to inhibit cell proliferation in
several cancer cell lines including prostate (Ouadid-Ahidouch and Ahidouch 2013).
In prostate cancer cells, KV channel is quite prominently expressed and involved in
cell proliferation (Prevarskaya et al. 2007). Blockade of KV channel by K+ channel
blocker 4-aminopyridine (4-AP) inhibited cell growth in both androgen-sensitive
(AT-2) and androgen-insensitive (MAT-LyLu) rat prostate cancer cell lines (Fraser
et al. 2000). Similarly, the channel blockers, dequalinium, amiodarone, and
glibenclamide have shown to induce apoptosis in PC-3 cells (Abdul and Hoosein
2002). Characterization of Kv channel in LNCaP and PC-3 Cells is presented in
Fig. 22.8, Concentration-dependent effect of piperine on IK in LNCaP cells
Fig. 22.9 and Concentration-dependent effect of piperine on IK in PC-3 cells
Fig. 22.10 (George et al. 2019; Rauscher et al. 2000).
22.23 Piperine Impairs the Migration and T
Cell-Activating Function of Dendritic Cells
Group of scientist attribute piperine-mediated inhibition of DC migration to
impairment of the chemokine receptor switch from CCR5 to CCR7 since CCL21
causes DC migration via stimulation of CCR7 (Yoshida et al. 1998). Reduced
in vivo migration of piperine-treated DCs was likely also caused by reduced
expression of CCR7. In addition, piperine-treated DCs exhibited decreased
LPS-induced expression of CD40 and MHC II molecules, as well as reduced
synthesis of the pro-inflammatory cytokines, TNF-a, IL-6, MCP-1. Furthermore,
exposure to piperine caused a significant decrease in MHC II high-expressing DC,
which is indicative of a reduction in highly mature DCs (Lutz et al. 1999). Taken
together, these findings suggest that exposure to piperine caused DCs to retain an
immature or semi-mature DC phenotype in spite of TLR4 stimulation with LPS.
Interestingly, piperine-treated DCs have increased phagocytic activity (Bae et al.
2012), which is also consistent with an immature DC phenotype. Our findings are in
776
N. Sachan et al.
Cancer Treatment
The concept of KV channel as therapeutic target for prostate cancer treatment attracts
increasing interest, but the lack of effective and selective KV channel modulators has
hindered the progression of treatment strategy (Schönherr 2005). Exploring the
functional properties of ion channels in cancer progression and metastatic behavior
is emerging as a novel approach for the development of effective anticancer treatment. Potassium (K+) channels in the plasma membrane of tumor cells contribute to
a wide range of cellular processes including cell cycle progression, cell proliferation,
and apoptosis (Ouadid-Ahidouch and Ahidouch 2008). In particular, K+ channels
play a crucial role in cell proliferation, as its activation is a prime factor for cell cycle
progression through early G1 phase of the cell cycle (Wonderlin and Strobl 1996).
Hence, the blockage of K+ channel activity has shown to inhibit cell proliferation in
several cancer cell lines including prostate (Ouadid-Ahidouch and Ahidouch 2013).
In prostate cancer cells, KV channel is quite prominently expressed and involved in
cell proliferation (Prevarskaya et al. 2007). Blockade of KV channel by K+ channel
blocker 4-aminopyridine (4-AP) inhibited cell growth in both androgen-sensitive
(AT-2) and androgen-insensitive (MAT-LyLu) rat prostate cancer cell lines (Fraser
et al. 2000). Similarly, the channel blockers, dequalinium, amiodarone, and
glibenclamide have shown to induce apoptosis in PC-3 cells (Abdul and Hoosein
2002). Characterization of Kv channel in LNCaP and PC-3 Cells is presented in
Fig. 22.8, Concentration-dependent effect of piperine on IK in LNCaP cells
Fig. 22.9 and Concentration-dependent effect of piperine on IK in PC-3 cells
Fig. 22.10 (George et al. 2019; Rauscher et al. 2000).
22.23 Piperine Impairs the Migration and T
Cell-Activating Function of Dendritic Cells
Group of scientist attribute piperine-mediated inhibition of DC migration to
impairment of the chemokine receptor switch from CCR5 to CCR7 since CCL21
causes DC migration via stimulation of CCR7 (Yoshida et al. 1998). Reduced
in vivo migration of piperine-treated DCs was likely also caused by reduced
expression of CCR7. In addition, piperine-treated DCs exhibited decreased
LPS-induced expression of CD40 and MHC II molecules, as well as reduced
synthesis of the pro-inflammatory cytokines, TNF-a, IL-6, MCP-1. Furthermore,
exposure to piperine caused a significant decrease in MHC II high-expressing DC,
which is indicative of a reduction in highly mature DCs (Lutz et al. 1999). Taken
together, these findings suggest that exposure to piperine caused DCs to retain an
immature or semi-mature DC phenotype in spite of TLR4 stimulation with LPS.
Interestingly, piperine-treated DCs have increased phagocytic activity (Bae et al.
2012), which is also consistent with an immature DC phenotype. Our findings are in
776
N. Sachan et al.