Abstract
Abstract
Phytochemicals of natural origin constitutes very initiative field of anticancer drug discovery. Annona sp. and Solanum nigrum are folk herbs with reported use for the treatment of several neoplasias. Natural herb products and folk medicine might not be potent anticancer remedies and are recommended for combination therapy. In the current work, we mathematically evaluated the influence of combining standardized extracts of A. cherimola and S. nigrum to the cytotoxic profile of 5-FU against head and neck cancer cells (HEP-2). Cytotoxicity assessment and combination analysis were calculated after MTT assays followed by fitting to Emax model and calculating the combination index (CI-value). After 24 h exposure, both A. cherimola and S. nigrum extracts were more potent than 5-FU with IC50 of 29.4±4.4, 7.3±1.3 and 3.4±4.4 µg/ml, respectively. Both A. cherimola and S. nigrum extracts significantly decreased the IC50 of 5-FU to 5.2±0.55 and 7.6±0.85 µg/ml, respectively; however the CI-values were indicative of additive and antagonistic interactions, respectively (0.91 and 2.49, respectively). After 48 h of exposure, the IC50 of 5-FU, A. cherimola and S. nigrum extracts were 3.1±0.45, 0.87±0.22 and 7.2±0.65 µg/ml, respectively. Similarly, combination of A. cherimola and S. nigrum extracts with 5-FU showed additive and antagonistic interaction with CI-values of 1.05 and 3.37, respectively. After 72 h of exposure, the IC50 of 5-FU, A. cherimola and S. nigrum extracts were 1.9±0.1, 2.1±0.24 and 2.1±0.1 µg/ml, respectively. Similarly, combination of A. cherimola and S. nigrum extracts with 5-FU showed additive and antagonistic interaction with CI-values of 1.2 and 2.21, respectively. Then, CnT model was used to assess the relative influence of drug concentration and exposure time on the cytotoxic profile of treatments under investigation. For S. nigrum and its combination with 5-FU, n-values were 0.9 and 0.63 which is indicative of relatively high influence of drug concentration. On the other hand, n-value for 5-FU treatment was 0.37; this indicates higher influence of drug exposure time compared to other treatment. The n-values of A. cherimola and its combination with 5-FU were 0.51 and 0.54, respectively; this indicate comparable influence of both drug concentration and exposure time. As a confirmatory measure, expression of the apoptotic gene, BAX, was increased after 5-FU combination with A. cherimola and decreased after combination with S. nigrum. In conclusion, some natural herb remedies such as A. cherimola might influence the cytotoxic profile of 5-FU and particularly after short exposure time; while on the other hand, some herb remedies such as S. nigrum significantly antagonizes its cytotoxic activity against head and neck cancer cells.
Citation Format: Serag Eldin I. Elbehairi, Aly F. Mohamed, Nahla G. Mohamed, Mohammad I. Basuony, Mahmoud M. Salem, Metwally M. Montaser, Mohammad Y. Alfaifi, Ayman M. Noreddin, Ahmed M. Al-Abd. Time dependent analysis for the combination of standardized Annona cherimola and Solanum nigrum extracts with 5-FU against head and neck cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1085. doi:10.1158/1538-7445.AM2017-1085