Comparative Assessment of the Antioxidant and Anticancer Activities of Plicosepalus acacia and Plicosepalus curviflorus: Metabolomic Profiling and In Silico Studies

Enas E Eltamany; Marwa S Goda; Mohamed S Nafie; Abdelghafar M Abu-Elsaoud; Rawan H Hareeri; Mohammed M Aldurdunji; Sameh S Elhady; Jihan M Badr; Nermeen A Eltahawy

doi:10.3390/antiox11071249

Comparative Assessment of the Antioxidant and Anticancer Activities of Plicosepalus acacia and Plicosepalus curviflorus: Metabolomic Profiling and In Silico Studies

Antioxidants (Basel). 2022 Jun 25;11(7):1249. doi: 10.3390/antiox11071249.

Authors

Enas E Eltamany¹, Marwa S Goda¹, Mohamed S Nafie², Abdelghafar M Abu-Elsaoud³, Rawan H Hareeri⁴, Mohammed M Aldurdunji⁵, Sameh S Elhady⁶, Jihan M Badr¹, Nermeen A Eltahawy¹

Affiliations

¹ Department of Pharmacognosy, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt.
² Department of Chemistry, Faculty of Science, Suez Canal University, Ismailia 41522, Egypt.
³ Department of Botany and Microbiology, Faculty of Science, Suez Canal University, Ismailia 41522, Egypt.
⁴ Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
⁵ Department of Clinical Pharmacy, College of Pharmacy, Umm Al-Qura University, P.O. Box 13578, Makkah 21955, Saudi Arabia.
⁶ Department of Natural Products, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia.

Abstract

This study presents a comparison between two mistletoe plants-P. acacia and P. curviflorus-regarding their total phenolic contents and antioxidant and anticancer activities. P. curviflorus exhibited a higher total phenolics content (340.62 ± 19.46 mg GAE/g extract), and demonstrated higher DPPH free radical scavenging activity (IC₅₀ = 48.28 ± 3.41µg/mL), stronger reducing power (1.43 ± 0.54 mMol Fe⁺²/g) for ferric ions, and a greater total antioxidant capacity (41.89 ± 3.15 mg GAE/g) compared to P. acacia. The cytotoxic effects of P. acacia and P. curviflorus methanol extracts were examined on lung (A549), prostate (PC-3), ovarian (A2780) and breast (MDA-MB-231) cancer cells. The highest anticancer potential for the two extracts was observed on PC-3 prostate cancer cells, where P. curviflorus exhibited more pronounced antiproliferative activity (IC₅₀ = 25.83 μg/mL) than P. acacia (IC₅₀ = 34.12 μg/mL). In addition, both of the tested extracts arrested the cell cycle at the Pre-G1 and G1 phases, and induced apoptosis. However, P. curviflorus extract possessed the highest apoptotic effect, mediated by the upregulation of p53, Bax, and caspase-3, 8 and 9, and the downregulation of Bcl-2 expression. In the pursuit to link the chemical diversity of P. curviflorus with the exhibited bioactivities, its metabolomic profiling was achieved by the LC-ESI-TOF-MS/MS technique. This permitted the tentative identification of several phenolics-chiefly flavonoid derivatives, beside some triterpenes and sterols-in the P. curviflorus extract. Furthermore, all of the metabolites in P. curviflorus and P. acacia were inspected for their binding modes towards both CDK-2 and EGFR proteins using molecular docking studies in an attempt to understand the superiority of P. curviflorus over P. acacia regarding their antiproliferative effect on PC-3 cancer cells. Docking studies supported our experimental results; with all of this taken together, P. curviflorus could be regarded as a potential prospect for the development of chemotherapeutics for prostate cancer.

Keywords: P. acacia; P. curviflorus; anticancer; antioxidant; chemical profiling; docking studies; drug discovery; industrial development.

Grants and funding

This research was funded by the Deanship of Scientific Research (DSR) at King Abdulaziz University (KAU), Jeddah, Saudi Arabia, under grant number RG-44-166-43.