1. HPLC-ESI/MS-MS metabolic profiling of white pitaya fruit and cytotoxic potential against cervical cancer: Comparative studies, synergistic effects, and molecular mechanistic approaches.
- Author
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El-Nashar HAS, Al-Azzawi MA, Al-Kazzaz HH, Alghanimi YK, Kocaebli SM, Alhmammi M, Asad A, Salam T, El-Shazly M, and Ali MAM
- Subjects
- Humans, Chromatography, High Pressure Liquid methods, HeLa Cells, Female, Animals, Vero Cells, Chlorocebus aethiops, Seeds chemistry, Antineoplastic Agents, Phytogenic pharmacology, Flavonoids pharmacology, Flavonoids analysis, Antioxidants pharmacology, Phenols pharmacology, Phenols analysis, Metabolomics methods, Uterine Cervical Neoplasms drug therapy, Uterine Cervical Neoplasms metabolism, Fruit chemistry, Plant Extracts pharmacology, Plant Extracts chemistry, Spectrometry, Mass, Electrospray Ionization methods, Tandem Mass Spectrometry methods, Cactaceae chemistry, Apoptosis drug effects, Cisplatin pharmacology, Drug Synergism
- Abstract
Natural approach became a high demand for the prevention and treatment of such diseases for their proven safety and efficacy. This study is aimed to perform comparative phytochemical analysis of white pitaya (Hylocereus undatus) peel, pulp and seed extracts via determination of total flavonoid content, phenolic content, and antioxidant capacity, coupled with HPLC-ESI/MS-MS analysis. Further, we evaluated the synergistic cytotoxic potential with Cisplatin against cervical cancer cells with investigation of underlying mechanism. The highest content of phenolics and antioxidants were found in both seed and peel extracts. The HPLC-ESI/MS-MS revealed identification of flavonoids, phenolic acids, anthocyanin glycosides, lignans, stilbenes, and coumarins. The cytotoxicity effects were evaluated by MTT assay against prostate, breast and cervical (HeLa) and Vero cell lines. The seed and peel extracts showed remarkable cytotoxic effect against all tested cell lines. Moreover, the selectivity index confirmed high selectivity of pitaya extracts to cancer cells and safety on normal cells. The combined therapy with Cisplatin effectively enhanced its efficacy and optimized the treatment outcomes, through the apoptotic ability of pitaya extracts in HeLa cells, as evaluated by flow cytometry. Besides, RT-PCR and western blotting analysis showed downregulation of Bcl-2 and overexpression of P53, BAX among HeLa cells treated with pitaya extracts, which eventually activated apoptosis process. Thus, pitaya extract could be used as adjuvant therapy with cisplatin for treatment of cervical cancer. Furthermore, in-vivo extensive studies on the seed and peel extracts, and their compounds are recommended to gain more clarification about the required dose, and side effects., Competing Interests: Declaration of Competing Interest The authors claimed to have no possible conflicts of interest. Conflict of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)
- Published
- 2024
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