Abstract
Abstract
The use of total standardized plant extracts is frequently used in low-income countries for several diseases. Solanum sp. and Annona sp. are edible folk herbs with reported uses for the treatment of several malignancies. Natural herb products and folk medicine might not be a potent anticancer and might be recommended for combination therapy. 5- FU is a commonly used antimetabolite chemotherapeutic agent used for the treatment of several neoplastic disorders. In the current work, we mathematically evaluated the influence of adding total standardized extract of A. cherimola and S. nigrum to the cytotoxic profile of 5-FU in head and neck cancer cells. Cytotoxicity assessment and combination analysis were calculated after MTT assays followed by fitting to the 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‘s 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‘s 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‘s 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, a combination of A. cherimola or 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‘s 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, a 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, the 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 the relatively high influence of drug concentration. On the other hand, the n-value for 5-FU treatment was 0.37; this indicates a higher influence of drug exposure time compared to other treatments. The n-values of A. cherimola and its combination with 5-FU were 0.51 and 0.54, respectively; this indicates a comparable influence of both drug concentration and exposure time. Further PCR analysis showed over-expression of the apoptotic gene, BAX, after 5-FU combination with A. cherimola and decreased after combination with S. nigrum. In conclusion, some natural herbal 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 herbal remedies such as S. nigrum significantly antagonize its cytotoxic activity against head and neck cancer cells and should be avoided during the treatment with 5-FU
Citation Format: Serag Eldin I. Elbehairi, Fahad A. Alabbasi, Aly F. Mohamed, Nahla G. Mohamed, Mohammad I. Basuony, Mahmoud M. Salem, Metwaly M. Montaser, Mohammad Y. Alfaifi, Safaa Y. Eid, Ahmed M. Al-Abd. Mathematical analysis for the combinatorial cytotoxic properties of the standardized extract of Annona cherimola or Solanum nigrum with 5-FU against head and neck cancer cells [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6561.