Home | Articles
Published on:May 2021
Indian Journal of Pharmaceutical Education and Research, 2021; 55(2):556-565
Original Article | doi:10.5530/ijper.55.2.94

Lyophilized Fruit Juice of Citrus sinensis Triggers Mitochondria-mediated Apoptosis via Downregulation of PI3K/AKT in MCF-7 Cell Line

Authors and affiliation (s):

Jayasindu Mathiyazhagan1, John Arul Daniel1, George Priya C. Doss1, Rama Jayaraj2, Kodiveri Muthukaliannan Gothandam1,*

1School of Bio Sciences and Technology, Vellore Institute of Technology (VIT), Vellore-14, Tamil Nadu, INDIA.

2Theme Lead, Flinders NT, Flinders University, Northern Territory 0909, AUSTRALIA.


Background: Breast cancer is prevalent cancer among women and a major cause of death worldwide due to various genetic and environmental factors. Citrus sinensis is widely taken fruit juice in most countries that are believed to reduce breast cancer risk. However, the mechanism through which it acts remains unclear. Our objective was to explore the mechanism through which Citrus sinensis acts as a cytotoxic agent. Materials and Methods: FT-IR and GC-MS analyses of lyophilzed orange juice (LOJ) were performed to find phytocompounds that were subjected to in silico docking analysis against phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway. The proteins that showed the low free energy of binding was taken for gene expression analysis. RT-PCR analysis was carried out to observe PI3K/AKT/mTOR genes inhibition in LOJ treated cells. Cytotoxicity, apoptosis, caspase 9 activity were performed against the human breast cancer cell line (MCF-7). Results: The docking analysis against PI3K/AKT/mTOR with LOJ compounds showed the best interactions. Further down-regulation of PI3K/AKT and moderate up-regulation of mTOR was confirmed using gene expression analysis. LOJ showed concentration-dependent cytotoxicity, apoptosis, decreased mitochondrial membrane stability and caspase 9 against the MCF-7 cell line. Conclusion: This study concludes that LOJ can induce apoptosis in MCF-7 cells via PI3K and AKT inhibition.

Key words: Lyophilized orange juice, Molecular docking, Apoptosis, MCF-7 cell line, PI3K/AKT/mTOR.



Impact Factor

IJPER - An Official Publication of Association of Pharmaceutical Teachers of India is pleased to announce continued growth in the Latest Release of Journal Citation Reports (source: Web of Science Data).


Impact Factor® as reported in the 2021 Journal Citation Reports® (Clarivate Analytics, 2022): 0.843

The Official Journal of Association of Pharmaceutical Teachers of India (APTI)
(Registered under Registration of Societies Act XXI of 1860 No. 122 of 1966-1967, Lucknow)

Indian Journal of Pharmaceutical Education and Research (IJPER) [ISSN-0019-5464] is the official journal of Association of Pharmaceutical Teachers of India (APTI) and is being published since 1967.


IJPER uses reference linking service using Digital Object Identifiers (DOI) by Crossref. Articles from the year 2013 are being assigned DOIs for its permanent URLs