HPLC-ESI/MS-MS metabolic profiling of white pitaya fruit and cytotoxic potential against cervical cancer: Comparative studies, synergistic effects, and molecular mechanistic approaches

• Published in: Journal of pharmaceutical and biomedical analysis 2024-07, Vol.244, p.116121, Article 116121
• Main Authors: El-Nashar, Heba A.S., Al-Azzawi, Mahmood A., Al-Kazzaz, Hassan Hadi, Alghanimi, Yasemin Khudiar, Kocaebli, Shaden Mohamed, Alhmammi, Moaz, Asad, Ahmed, Salam, Tarek, El-Shazly, Mohamed, Ali, Mohamed A.M.
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents, Phytogenic - pharmacology; Antioxidants - pharmacology; Apoptosis - drug effects; Cactaceae - chemistry; Cervical cancer; Chlorocebus aethiops; Chromatography, High Pressure Liquid - methods; Cisplatin - pharmacology; Drug Synergism; Female; Flavonoids - analysis; Flavonoids - pharmacology; Flow cytometry; Fruit - chemistry; HeLa; HeLa Cells; Humans; Hylocereus undatus; Metabolomics - methods; Phenolics; Phenols - analysis; Phenols - pharmacology; Plant Extracts - chemistry; Plant Extracts - pharmacology; Seeds - chemistry; Spectrometry, Mass, Electrospray Ionization - methods; Tandem Mass Spectrometry - methods; Uterine Cervical Neoplasms - drug therapy; Uterine Cervical Neoplasms - metabolism; Vero Cells; White pitaya
• ISSN: 0731-7085; 1873-264X; 1873-264X
• DOI: 10.1016/j.jpba.2024.116121

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. •White pitaya is a well-known edible fruit belonging to the family Cactaceae.•Comparative phytochemical studies of fruit parts were performed.•The anticancer efficacy was investigated in cervical, prostate, and breast cells.•Synergism of extracts with cisplatin was studied.•RT-PCR and western blotting analysis were carried out.