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The recent article by Westekemper et al. was highly interesting [1]. Nemorosone may exert a number of anti-neoplastic effects in a number of systemic malignancies.
Nemorosone acts on estrogen receptors α, and thereby attenuates tumor growth in breast malignancies. Nemorosone administration results in attenuated expression of pERK1/2 and pAkt [2]. The resulting effect is decreased intra-tumoral apoptosis in G0/G1 phase blockage.
Nemorosone is also effective in the management of gastro-intestinal malignancies. For instance, it activates the unfolded protein response (UPR) network in pancreatic malignancies and thereby accentuates tumor apoptosis in these cancers [3]. UPR-mediated apoptosis is regulated primarily by DNA damage inducible transcript 3. Simultaneously, the mitochondrial membrane potential is reduced. A simultaneous accentuation of cytochrome c release is seen. Nemorosone also exerts anti- proliferative effects in leukemias by altering hematopoiesis. It mediates these effects in part by modulating Akt/PKB function [4]. The key advantage of nemorosone is that it helps overcome chemo-resistance in leukemias. A simultaneous decline in cyclins A and c-Myb is noticed. Down-regulation of p38 MAPK also accompanies nemorosone administration in leukemia’s.
Nemorosone is also effective in inhibiting growth in androgen-dependent prostate malignancies. For instance, 7-epi-nemorosone targets MEK1/2 and thereby induces cytotoxic effects in prostate carcinomas [5]. Nemorosone administration results in a decline in S phase cells and an increase in G0/G1 phase cells. CDK 4/6 is also down-regulated. Attenuation of PSA levels occurs subsequently, resulting in better tumor growth control. Nemorosone is also effective in the management of intracranial tumors such as neuroblastomas. It mediates these anti-neoplastic effects by down-regulating N-myc levels [6]. An increase in the activity of caspase-3, and simultaneous inhibition of Akt/PKB also contributes to these anti-neoplastic effects.
The above examples clearly illustrate the effectiveness of nemorosone in attenuating tumor growth in a number of systemic malignancies.
References
Westekemper H, Freistuehler M, Bornfeld N, Steuhl KP, Scheulen M, Hilger RA (2013) Chemosensitivity of conjunctival melanoma cell lines to target-specific chemotherapeutic agents. Graefes Arch Clin Exp Ophthalmol 251:279–284
Popolo A, Piccinelli AL, Morello S (2011) Cytotoxic activity of nemorosone in human MCF-7 breast cancer cells. Can J Physiol Pharmacol 89:50–57
Holtrup F, Bauer A, Fellenberg K, Hilger RA, Wink M, Hoheisel JD (2011) Microarray analysis of nemorosone-induced cytotoxic effects on pancreatic cancer cells reveals activation of the unfolded protein response (UPR). Br J Pharmacol 162:1045–1059
Diaz-Carballo D, Malak S, Freistuhler M, Elmaagacli A, Bardenheuer W, Reusch HP (2008) Nemorosone blocks proliferation and induces apoptosis in leukemia cells. Int J Clin Pharmacol Ther 46:428–439
Diaz-Carballo D, Gustmann S, Acikelli AH (2012) 7-epi-nemorosone from Clusia rosea induces apoptosis, androgen receptor down-regulation and dysregulation of PSA levels in LNCaP prostate carcinoma cells. Phytomedicine 19(14):1298–1306 [PMID: 22981203]. doi: 10.1016/j.phymed.2012.08.004
Diaz-Carballo D, Malak S, Bardenheuer W, Freistuehler M, Reusch HP (2008) Cytotoxic activity of nemorosone in neuroblastoma cells. J Cell Mol Med 12:2598–2608
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Kapoor, S. Nemorosone and its emerging anti-neoplastic effects. Graefes Arch Clin Exp Ophthalmol 251, 2487 (2013). https://doi.org/10.1007/s00417-013-2395-3
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DOI: https://doi.org/10.1007/s00417-013-2395-3