108
S. B. Christensen et al.
144. Martin-Perez R, Palacios C, Yerbes R, Cano-Gonzalez A, Iglesias-Serret D, Gil J, Reginato
MJ, Lopez-Rivas A (2014) Activated ERBB2/HER2 licenses sensitivity to apoptosis upon
endoplasmic reticulum stress through a PERK-dependent pathway. Cancer Res 74:1766
145. Engedal N, Korkmaz CG, Saatcioglu F (2002) C-Jun N-terminal kinase is required for phorbol
ester- and thapsigargin-induced apoptosis in the androgen responsive prostate cancer cell line
LNCaP. Oncogene 21:1017
146. Engedal N, Torgersen ML, Guldvik IJ, Barfeld SJ, Bakula D, Satre F, Hagen LK, Patterson
JB, Proikas-Cezanne T, Seglen PO, Simonsen A, Mills IG (2013) Modulation of intracellular
calcium homeostasis blocks autophagosome formation. Autophagy 9:1475
147. Pinski J, Parikh A, Bova GS, Isaacs JT (2001) Therapeutic implications of enhanced G0/G1
checkpoint control induced by coculture of prostate cancer cells with osteoblasts. Cancer Res
61:6372
148. Xu C, Ma H, Inesi G, Al-Shawi MK, Toyoshima C (2004) Specific structural requirements
for the inhibitory effect of thapsigargin on the Ca 2+ ATPase SERCA. J Biol Chem 279:17973
149. Thastrup O, Cullen PJ, Drøbak BK, Hanley MR, Dawson AP (1990) Thapsigargin, a tumor
promoter, discharges intracellular Ca 2+ stores by specific inhibition of the endoplasmic
reticulum Ca 2+ -ATPase. Proc Natl Acad Sci USA 87:2466
150. Thastrup O, Dawson AP, Scharff O, Foder B, Cullen PJ, Drobak BK, Bjerrum PJ, Christensen
SB, Hanley MR (1989) Thapsigargin, a novel molecular probe for studying intracellular
calcium release and storage. Agents Actions 27:17
151. Søhoel H, Lund Jensen A-M, Moller JV, Nissen P, Denmeade SR, Isaacs JT, Olsen CE, Christensen SB (2006) Natural products as starting materials for development of second-generation
SERCA inhibitors targeted towards prostate cancer cells. Bioorg Med Chem 14:2810
152. Jakobsen CM, Denmeade SR, Isaacs JT, Gady A, Olsen CE, Christensen SB (2001) Design,
synthesis, and pharmacological evaluation of thapsigargin analogues for targeting apoptosis
to prostatic cancer cells. J Med Chem 44:4696
153. Caspersen C, Treiman M (1995) Thapsigargin discriminates strongly between Ca (+2) -ATPase
phosphorylated intermediates with different subcellular distributions in bovine adrenal
chromaffin cells. FEBS Lett 377:31
154. Wictome M, Holub M, East JM, Lee AG (1994) The importance of the hydroxyl moieties for
inhibition of the Ca 2+ -ATPase by trilobolide and 2,5-di(tert-butyl)-1,4-benzohydroquinone.
Biochem Biophys Res Commun 199:916
155. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A (2018) Global cancer
statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers
in 185 countries. CA Cancer J Clin 68:394
156. Siegel RL, Miller KD, Jemal A (2019) Cancer statistics 2019. CA Cancer J Clin 69:7
157. Chan KS, Koh CG, Li HY (2012) Mitosis-targeted anti-cancer therapies: where they stand.
Cell Death Dis 3:e411
158. Shackney SE, McCormack GW, Cuchural GJ Jr (1978) Growth rate patterns of solid tumors
and their relation to responsiveness to therapy: an analytical review. Ann Intern Med 89:107
159. Akinboye ES, Brennen WN, Denmeade SR, Isaacs JT (2019) Albumin-linked prostatespecific antigen-activated thapsigargin- and niclosamide-based molecular grenades targeting
the microenvironment in metastatic castration-resistant prostate cancer. Asian J Urol 6:99
160. Isaacs JT (2005) New strategies for the medical treatment of prostate cancer. BJU Int 96(Suppl
2):35
161. Berges RR, Vukanovic J, Epstein JI, Carmichel M, Cisek L, Johnson DE, Veltri RW, Walsh
PC, Isaacs JT (1995) Implication of cell kinetic changes during the progression of human
prostatic cancer. Clin Cancer Res 1:473
162. Rautio J, Karkkainen J, Sloan KB (2017) Prodrugs—recent approvals and a glimpse of the
pipeline. Eur J Pharm Sci 109(Suppl):146
163. Aloysius H, Hu L (2015) Targeted prodrug approaches for hormone refractory prostate cancer.
Med Res Rev 35:554
164. Sharma SK, Bagshawe KD (2017) Antibody directed enzyme prodrug therapy (ADEPT):
trials and tribulations. Adv Drug Deliv Rev 118:2
S. B. Christensen et al.
144. Martin-Perez R, Palacios C, Yerbes R, Cano-Gonzalez A, Iglesias-Serret D, Gil J, Reginato
MJ, Lopez-Rivas A (2014) Activated ERBB2/HER2 licenses sensitivity to apoptosis upon
endoplasmic reticulum stress through a PERK-dependent pathway. Cancer Res 74:1766
145. Engedal N, Korkmaz CG, Saatcioglu F (2002) C-Jun N-terminal kinase is required for phorbol
ester- and thapsigargin-induced apoptosis in the androgen responsive prostate cancer cell line
LNCaP. Oncogene 21:1017
146. Engedal N, Torgersen ML, Guldvik IJ, Barfeld SJ, Bakula D, Satre F, Hagen LK, Patterson
JB, Proikas-Cezanne T, Seglen PO, Simonsen A, Mills IG (2013) Modulation of intracellular
calcium homeostasis blocks autophagosome formation. Autophagy 9:1475
147. Pinski J, Parikh A, Bova GS, Isaacs JT (2001) Therapeutic implications of enhanced G0/G1
checkpoint control induced by coculture of prostate cancer cells with osteoblasts. Cancer Res
61:6372
148. Xu C, Ma H, Inesi G, Al-Shawi MK, Toyoshima C (2004) Specific structural requirements
for the inhibitory effect of thapsigargin on the Ca 2+ ATPase SERCA. J Biol Chem 279:17973
149. Thastrup O, Cullen PJ, Drøbak BK, Hanley MR, Dawson AP (1990) Thapsigargin, a tumor
promoter, discharges intracellular Ca 2+ stores by specific inhibition of the endoplasmic
reticulum Ca 2+ -ATPase. Proc Natl Acad Sci USA 87:2466
150. Thastrup O, Dawson AP, Scharff O, Foder B, Cullen PJ, Drobak BK, Bjerrum PJ, Christensen
SB, Hanley MR (1989) Thapsigargin, a novel molecular probe for studying intracellular
calcium release and storage. Agents Actions 27:17
151. Søhoel H, Lund Jensen A-M, Moller JV, Nissen P, Denmeade SR, Isaacs JT, Olsen CE, Christensen SB (2006) Natural products as starting materials for development of second-generation
SERCA inhibitors targeted towards prostate cancer cells. Bioorg Med Chem 14:2810
152. Jakobsen CM, Denmeade SR, Isaacs JT, Gady A, Olsen CE, Christensen SB (2001) Design,
synthesis, and pharmacological evaluation of thapsigargin analogues for targeting apoptosis
to prostatic cancer cells. J Med Chem 44:4696
153. Caspersen C, Treiman M (1995) Thapsigargin discriminates strongly between Ca (+2) -ATPase
phosphorylated intermediates with different subcellular distributions in bovine adrenal
chromaffin cells. FEBS Lett 377:31
154. Wictome M, Holub M, East JM, Lee AG (1994) The importance of the hydroxyl moieties for
inhibition of the Ca 2+ -ATPase by trilobolide and 2,5-di(tert-butyl)-1,4-benzohydroquinone.
Biochem Biophys Res Commun 199:916
155. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A (2018) Global cancer
statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers
in 185 countries. CA Cancer J Clin 68:394
156. Siegel RL, Miller KD, Jemal A (2019) Cancer statistics 2019. CA Cancer J Clin 69:7
157. Chan KS, Koh CG, Li HY (2012) Mitosis-targeted anti-cancer therapies: where they stand.
Cell Death Dis 3:e411
158. Shackney SE, McCormack GW, Cuchural GJ Jr (1978) Growth rate patterns of solid tumors
and their relation to responsiveness to therapy: an analytical review. Ann Intern Med 89:107
159. Akinboye ES, Brennen WN, Denmeade SR, Isaacs JT (2019) Albumin-linked prostatespecific antigen-activated thapsigargin- and niclosamide-based molecular grenades targeting
the microenvironment in metastatic castration-resistant prostate cancer. Asian J Urol 6:99
160. Isaacs JT (2005) New strategies for the medical treatment of prostate cancer. BJU Int 96(Suppl
2):35
161. Berges RR, Vukanovic J, Epstein JI, Carmichel M, Cisek L, Johnson DE, Veltri RW, Walsh
PC, Isaacs JT (1995) Implication of cell kinetic changes during the progression of human
prostatic cancer. Clin Cancer Res 1:473
162. Rautio J, Karkkainen J, Sloan KB (2017) Prodrugs—recent approvals and a glimpse of the
pipeline. Eur J Pharm Sci 109(Suppl):146
163. Aloysius H, Hu L (2015) Targeted prodrug approaches for hormone refractory prostate cancer.
Med Res Rev 35:554
164. Sharma SK, Bagshawe KD (2017) Antibody directed enzyme prodrug therapy (ADEPT):
trials and tribulations. Adv Drug Deliv Rev 118:2