Naslov
Antitumor activity of anthrols that photochemically generate quinone methides or reactive oxygen species and their selectivity towards cancer stem cells

Autori
Uzelac, Lidija ; Škalamera, Đani ; Mlinarić-Majerski, Kata ; Basarić, Nikola ; Kralj, Marijeta

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
10th Joint Meeting on Medical Chemistry : Book of Abstracts / Basarić, Nikola ; Namjesnik, Danijel ; Perković, Ivana ; Stepanić, Višnja - Zagreb : Hrvatsko kemijsko društvo, 2017, 144-144

ISBN
978-953-55232-8-4

Skup
10th Joint Meeting of Medicinal Chemistry

Mjesto i datum
Dubrovnik, Hrvatska, 25.06.2017. - 28.06.2017

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
Cancer stem cells ; Antiproliferative activity ; Phototherapy, Anthracenes, Quinone methides

Sažetak
Cancer stem cells (CSCs) are a subpopulation of cancer cells that share properties of embryonic stem cells like pluripotency and self-renewal. They are responsible for tumor formation, relapse and metastasis and also exhibit resistance to a whole range of drugs with different cellular targets. Mechanisms of resistance include enhanced survival pathways, increased activation of drug efflux pumps and enhanced capability for reactive oxygen species (ROS) defense. Targeting CSC, rather than cancer cells in general, is a novel and highly promising strategy for cancer treatment.[1, 2] As a result of current treatments failing to target CSCs, novel therapies such as photodynamic therapy (PDT) are being investigated. PDT involves the treatment of cancer cells with an inactive and nontoxic photosensitizer (PS), which is activated by light with specific wavelength, matching its absorbance spectrum. This leads to reactive oxygen species (ROS) generation, which causes cancer cell death. Further development of cancer treatment approaches and search for new targets and compound leads, requires discovery and elucidation of novel phototherapy mechanisms on molecular level. A promising group of phototherapeutic agents are reactive intermediates - quinone methides (QMs). One of the methods for the generation of QMs is photodehydration or phototautomerization of phenol derivatives.[3, 4] The objective of the proposed research is to test anticancer potential of anthracene derivatives 1-4 that can generate either QMs, or ROS upon the irradiation with near visible light at λ > 400 nm. Special attention was put to demonstrate the potential selectivity of these compounds towards the cells with CSC-like properties. We performed a detailed photochemical and photobiological investigation on anthrol derivatives 1-4. While upon the excitation 1-2 can give QMs, 3-4 cannot undergo photodehydration and deliver QM, but lead to the singlet oxygen formation. Their activity was tested on a panel of human tumor cell lines (HCT116, MCF-7, H460 and SUM 159), as well as on a unique transgenic CSC model (HMLEshEcad/HMLEshGFP).[1] The antiproliferative ability was tested by MTT, colony formation assay, and cell cycle analysis. Confocal microscopy was used to demonstrate the localization of compounds in the cells, and ROS measurements were conducted to evaluate the ability of 3 and 4 to induce oxidative stress. We demonstrated an intriguing cytotoxic activity of anthrols, and selectivity towards CSC cell model of those that produced ROS. This study forms the basis for further research on cancer phototherapy, as well as for the elucidation of CSC selectivity based on oxidative stress activation.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Temeljne medicinske znanosti

POVEZANOST RADA