Abstract：
:Natural products are characterized by extreme structural diversity and thus they offer a unique source for the identification of novel anti-tumor agents. Herein, we report that the herbal substance acteoside being isolated by advanced phytochemical methods from Lippia citriodora leaves showed enhanced cytotoxicity against metastatic tumor cells; acted in synergy with various cytotoxic agents and it sensitized chemoresistant cancer cells. Acteoside was not toxic in physiological cellular contexts, while it increased oxidative load, affected the activity of proteostatic modules and suppressed matrix metalloproteinases in tumor cell lines. Intraperitoneal or oral (via drinking water) administration of acteoside in a melanoma mouse model upregulated antioxidant responses in the tumors; yet, only intraperitoneal delivery suppressed tumor growth and induced anti-tumor-reactive immune responses. Mass-spectrometry identification/quantitation analyses revealed that intraperitoneal delivery of acteoside resulted in significantly higher, vs. oral administration, concentration of the compound in the plasma and tumors of treated mice, suggesting that its in vivo anti-tumor effect depends on the route of administration and the achieved concentration in the tumor. Finally, molecular modeling studies and enzymatic activity assays showed that acteoside inhibits protein kinase C. Conclusively, acteoside holds promise as a chemical scaffold for the development of novel anti-tumor agents.
journal_name
Redox Bioljournal_title
Redox biologyauthors
Cheimonidi C,Samara P,Polychronopoulos P,Tsakiri EN,Nikou T,Myrianthopoulos V,Sakellaropoulos T,Zoumpourlis V,Mikros E,Papassideri I,Argyropoulou A,Halabalaki M,Alexopoulos LG,Skaltsounis AL,Tsitsilonis OE,Aligiannis NN,Tdoi
10.1016/j.redox.2018.02.015subject
Has Abstractpub_date
2018-06-01 00:00:00pages
169-178issn
2213-2317pii
S2213-2317(18)30040-5journal_volume
16pub_type
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