| Title: | TMPE Derived from Saffron Natural Monoterpene as Cytotoxic and Multidrug Resistance Reversing Agent in Colon Cancer Cells |
| Author(s): | Sroda-Pomianek K; Palko-Labuz A; Pola A; Ferens-Sieczkowska M; Wesolowska O; Koziol A; |
| Address: | "Department of Biophysics and Neurobiology, Wroclaw Medical University, ul. Chalubinskiego 3, 50-368 Wroclaw, Poland. Department of Chemistry and Immunochemistry, Wroclaw Medical University, ul. M. Sklodowskiej-Curie 48/50, 50-369 Wroclaw, Poland" |
| ISSN/ISBN: | 1422-0067 (Electronic) 1422-0067 (Linking) |
| Abstract: | "Terpenes constitute one of the largest groups of natural products. They exhibit a wide range of biological activities including antioxidant, anticancer, and drug resistance modulating properties. Saffron extract and its terpene constituents have been demonstrated to be cytotoxic against various types of cancer cells, including breast, liver, lung, pancreatic, and colorectal cancer. In the present work, we have studied anticancer properties of TMPE, a newly synthesized monoterpene derivative of beta-cyclocitral-the main volatile produced by the stigmas of unripe crocuses. TMPE presented selective cytotoxic activity to doxorubicin-resistant colon cancer cells and was identified to be an effective MDR modulator in doxorubicin-resistant cancer cells. Synergy between this derivative and doxorubicin was observed. Most probably, TMPE inhibited transport activity of ABCB1 protein without affecting its expression level. Analysis of TMPE physicochemical parameters suggested it was not likely to be transported by ABCB1. Molecular modeling showed TMPE being more reactive molecule than the parental compound-beta-cyclocitral. Analysis of electrostatic potential maps of both compounds prompted us to hypothesize that reduced reactivity as well as susceptibility to electrophilic attack were related to the lower general toxicity of beta-cyclocitral. All of the above pointed to TMPE as an interesting candidate molecule for MDR reversal in cancer cells" |
| Keywords: | "ATP Binding Cassette Transporter, Subfamily B, Member 1/antagonists & inhibitors/chemistry/metabolism Aldehydes/chemistry *Antineoplastic Agents/chemical synthesis/pharmacology Binding Sites Cell Proliferation/drug effects Colonic Neoplasms/*metabolism Cr;" |
| Notes: | "MedlineSroda-Pomianek, Kamila Palko-Labuz, Anna Pola, Andrzej Ferens-Sieczkowska, Miroslawa Wesolowska, Olga Koziol, Agata eng Switzerland 2020/10/18 Int J Mol Sci. 2020 Oct 13; 21(20):7529. doi: 10.3390/ijms21207529" |
