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ORIGINAL RESEARCH article

Front. Pharmacol.

Sec. Experimental Pharmacology and Drug Discovery

Volume 16 - 2025 | doi: 10.3389/fphar.2025.1676006

This article is part of the Research TopicBiotechnology Frontiers in PharmacologyView all articles

In Vitro Antiproliferative Potential of Essential Oil Extract from Carica papaya L. Seeds Against Cervical Cancer

Provisionally accepted
Doaa SayedDoaa Sayed1Sally A Abdel-HalimSally A Abdel-Halim2Mohamed-Elamir F HegazyMohamed-Elamir F Hegazy2Salwa AljohaniSalwa Aljohani3Aljazi Abdullah AlrashidiAljazi Abdullah Alrashidi4Mohamed A El-DesoukyMohamed A El-Desouky1Hoda A. AhmedHoda A. Ahmed3Mariusz JaremkoMariusz Jaremko5Abdul-Hamid EmwasAbdul-Hamid Emwas6Demiana HannaDemiana Hanna1*
  • 1Cairo University Faculty of Science, Giza, Egypt
  • 2National Research Centre,, 33 El Bohouth St., Dokki 12622, Giza,, Egypt
  • 3Chemistry Department, Faculty of Science at Yanbu, Taibah University,, Yanbu, Saudi Arabia
  • 4Faculty of Science, Department of Chemistry, University of Hail, Hail, Saudi Arabia, Saudi Arabia, Saudi Arabia
  • 56Smart-Health Initiative (SHI) and Red Sea Research Center (RSRC), Division of Biological and Environmental Sciences and Engineering (BESE), King Abdullah University of Science and Technology, Thuwal, Jeddah, KAUST, Saudi Arabia
  • 67King Abdullah University of Science and Technology, Core Labs,, Thuwal, Saudi Arabia

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Cervical cancer, the third most common cancer worldwide, is primarily caused by human papillomavirus (HPV) infection. This study aimed to develop natural extracts from Carica papaya L. seeds using the hydrodistillation method to evaluate their anticancer effects against HeLa cells. The essential oil's phytochemical composition was analyzed using gas chromatography-mass spectrometry (GC-MS), revealing benzyl isothiocyanate as the dominant compound (99.49%). The cytotoxic effects of the oil on HeLa cell proliferation, apoptosis, cell cycle regulation, migration, and colony formation were investigated. Results demonstrated that the essential oil had a high cytotoxic effect, with an IC50 value of 16.78 µg/mL in the MTT assay. Apoptosis analysis indicated a significant increase in early and late apoptotic HeLa cells (23.45%). Flow cytometry revealed a G2/M phase arrest, which impeded cell division. The oil also exhibited a stronger inhibition of cancer cell migration (38.7%) than Methotrexate (45.9%). Additionally, the clonogenic assay revealed a drastic reduction in colony formation (0.004% surviving fraction, 0.25% plating efficiency). ELISA results showed a profound effect on apoptosis-related proteins, reducing BCL-2, MMP-2, and CDK1/cyclin B1 expression, supported by molecular docking studies comparing its efficacy to Methotrexate (−5.52, −6.29, and −5.75 vs −5.49, −5.44, and 5.18 kcal mol−, respectively). The findings suggest that Carica papaya seed essential oil may serve as a potential anticancer treatment for cervical cancer; however, further in vivo studies are required for validation in animal models.

Keywords: Carica papaya, Essential oil, HeLa cancer cell line, Apoptosis, Migration, molecular docking

Received: 29 Jul 2025; Accepted: 04 Sep 2025.

Copyright: © 2025 Sayed, Abdel-Halim, Hegazy, Aljohani, Alrashidi, El-Desouky, Ahmed, Jaremko, Emwas and Hanna. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Demiana Hanna, Cairo University Faculty of Science, Giza, Egypt

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

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