Unraveling the Ferroptosis-inducing Potential of Methanol Leaves Extract of Prosopis Juliflora Via Downregulation of SLC7A11 and GPX4 mRNA Expression in A549 Lung Cancer Cells

Nawaf Alshammari; Pratibha Pandey; Alya Redhwan; Hadeel R Bakhsh; Sorabh Lakhanpal; Safia Obaidur Rab; Ajay Singh; Mohd Saeed; Fahad Khan; Mohd Asif Shah

doi:10.2174/0109298673343133241011072425

Unraveling the Ferroptosis-inducing Potential of Methanol Leaves Extract of Prosopis Juliflora Via Downregulation of SLC7A11 and GPX4 mRNA Expression in A549 Lung Cancer Cells

Curr Med Chem. 2024 Oct 24. doi: 10.2174/0109298673343133241011072425. Online ahead of print.

Authors

Nawaf Alshammari¹, Pratibha Pandey^{2

3}, Alya Redhwan⁴, Hadeel R Bakhsh⁵, Sorabh Lakhanpal⁶, Safia Obaidur Rab⁷, Ajay Singh⁸, Mohd Saeed¹, Fahad Khan⁹, Mohd Asif Shah¹⁰

Affiliations

¹ Department of Biology, College of Science, University of Hail, Hail, Saudi Arabia.
² Centre for Research Impact and Outcome, Chitkara University Institute of Engineering and Technology, Chitkara University, Rajpura, 140401, Punjab, India.
³ Centre for Research Impact and Outcome, Chitkara College of Pharmacy, Chitkara University, Rajpura, 140401, Punjab, India.
⁴ College of Health and Rehabilitation Sciences, Coordinator of Microbiology and Immunology Unit at the Health Sciences Research Center, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi Arabia.
⁵ Department of Rehabilitation Sciences, College of Health and Rehabilitation Sciences, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh11671, Saudi Arabia.
⁶ School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab.
⁷ Department of Clinical Laboratory Sciences, College of Applied Medical Science, King Khalid University, Abha, Saudi Arabia.
⁸ School of Applied and Life Sciences, Uttaranchal University, Dehradun.
⁹ Center for Global Health Research Saveetha Medical College, Saveetha Institute of Medical and Technical Sciences, Chennai, India.
¹⁰ Kardan University, Parwane Du, 1001, Kabul, Afghanistan.

PMID: 39449336
DOI: 10.2174/0109298673343133241011072425

Abstract

Introduction: Prosopis juliflora has been employed in many traditional treatments. As evidenced by our earlier research, Prosopis juliflora leaf methanol extract (PJME) has a promising future in the fight against lung cancer. It may also be used in conjunction with other treatments to effectively manage lung cancer.

Aims and objective: The main objective of this study was to explore the potential of PJME to inhibit lung cancer in A549 cells, along with its underlying mechanisms of action.

Method: The antiproliferative effects were determined using MTT and LDH tests. Apoptosis- inducing capacity was evaluated using the DAPI staining, caspase-3 test, cytochrome C assay, PARP cleavage, and qRT-PCR. To investigate the mechanism of action of PJME in lung cancer, the levels of ROS, MMP, GSH, MDA, and specific ferroptosis indicators were measured.

Results: The experimental data of the current study indicated that exposure of A549 cells to PJME reduced cell viability and increased cellular cytotoxicity. The apoptosis-inducing ability of PJME in A549 cells was validated by enhanced nuclear condensation, level of the caspase- 3, cytochrome C, and PARP release. In addition, qRT-PCR investigations verified that the administration of PJME led to a decrease in the expression of anti-apoptotic gene Bcl2 while enhancing the mRNA level of pro-apoptotic genes, such as Bax and caspase-3, in A549 cells.

Conclusion: The study also found that PJME has the ability to activate ferroptosis pathways, as evidenced by elevated reactive oxygen species (ROS) generation, changes in the levels of antioxidant markers (MDA and GSH), and decreased expression of SLC7A11 and GPX4. The results of the present study clearly showed that PJME inhibited the proliferation of A549 cells and induced ferroptosis by reducing the expression of the important targets SLC7A11 and GPX4. Further research is necessary to fully understand the clinical efficacy of PJME before it can be investigated as supplemental or adjuvant therapy for lung cancer.

Keywords: Prosopis juliflora; anticancer; apoptosis; ferroptosis.; molecular target.