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

Doaa Sayed¹Sally A Abdel-Halim²Mohamed-Elamir F Hegazy²Salwa Aljohani³Aljazi Abdullah Alrashidi⁴Mohamed A El-Desouky¹Hoda A. Ahmed³Mariusz Jaremko⁵Abdul-Hamid Emwas⁶Demiana Hanna^1*

• 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

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.