Abstract
Abstract
Breast cancer remains the most common type of cancer in females, and remains to be one of the most leading causes of death worldwide. This led to increasing the interest to use adjuvant anti-cancer therapy to improve the efficacy of in-clinical use chemotherapeutic agents. Thymoquinone (TQ) is a naturally occurring bioactive compound which showed cumulative evidences of anticancer properties. Herein, we assessed the potential chemomodulatory effect of TQ as an adjuvant therapy in combination with paclitaxel (PTX) against breast cancer cells. Cytotoxic profiles of TQ alone or in combination with PTX were evaluated in MCF7 and T47D breast cancer cell lines. TQ showed cytotoxic effect against MCF7 and T47D cells with IC50’s of 64.93±14 µM and 165±2 µM, respectively. In MCF7, TQ did not change PTX’s IC50, and the combination index was indicative of antagonism (CI-value = 1.3). Similarly in T47D, combination of TQ with PTX increased PTX’s IC50 from 90±8 nM to 140±20 nM with CI-value of 1.5 indicating antagonism. However, it was found that TQ completely depleted PTX resistant fractions in both cancer cell lines under investigation. Moreover, apoptotic and autophagic cell death due to combination of PTX with TQ were significantly increased in T47D compared to PTX treatment alone by 5.6 and 1.7 folds, respectively. In MCF7, combination of TQ with PTX significantly increased autophagic cell death compared to PTX treatment alone. Furthermore, tumor associated stem cell clone (CD44(+)/CD24(-)/(low) was assessed by flow cytometry in MCF7 and T47D cells. TQ alone significantly decreased CD44+/CD24- tumor associated stem cell clone by 12.4±0.8%. In addition, combination of PTX with TQ further depleted CD44+/CD24- cell clone by 32.3±0.08%. Finally, TQ alone significantly downregulated TWIST-1, and upregulated SNAIL2 gene expression as an evidence to decreased cell resistance to PTX. In conclusion, TQ enhances PTX anticancer profile against breast cancer cells via depleting tumor associated stem cells clone rather than potentiating its direct cell killing effect.
Citation Format: Hanan A. Bashmail, Aliaa A. Alamoudi, Gehan A. Hegazy, Ghada M.A. Agabnoor, Abdulwahab Noorwali, Ahmed M. Al-Abd. Thymoquinone attenuates breast cancer cell resistance to paclitaxel via targeting tumor associated stem cell population [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2995.