An Investigation of the Antiproliferative Effect of Rhododendron luteum Extract on Cervical Cancer (HeLa) Cells via Nrf2 Signaling Pathway

Abstract

The aim of the present study was to investigate the role of Rhododendron luteum extract (RLE) in the induction of Nrf2‑related oxidative stress and endoplasmic reticulum (ER) stress in human cervical cancer (HeLa) cells. The antiproliferative effect of RLE on HeLa and fibroblast cells was determined using the MTT assay. The effects of RLE on the cell cycle, apoptosis, and production of reactive oxygen species (ROS) in HeLa cells were evaluated using fluorescent probes. The mRNA expression levels of Nrf2 [and its targets glutamate-cysteine ligase catalytic subunit (GCLC), and glucose-6-phosphate dehydrogenase (G6PD)], and C/EBP homologous protein (CHOP, an ER stress marker were determined using reverse transcription‑quantitative polymerase chain reaction (RT-PCR). The results demonstrated that RLE exhibited a selective cytotoxic effect (2.9-fold) on HeLa cells compared to fibroblast cells. RLE arrested the cell cycle at the S phase, and induced apoptosis, ER stress, and ROS formation. In addition, RLE significantly suppressed the expression levels of Nrf2, GCLC and G6PD (0.65, 0.69, and 0.54-fold, respectively) and increased the expression of CHOP (4.48-fold) in HeLa cells at 72 h of treatment (p < 0.05). These results show that the antiproliferative effect of RLE occurs through the Nrf2 and ER stress pathways, and the results should now be supported by further in vivo studies.

Disclosure Statement

None of the authors had any financial or personal relationships with other individuals or organizations that might have inappropriately influenced their work during the submission process.

Author Contributions

I.T., S.D., Y.A., and A.M. designed the study. S.D., and I.T., planned experiments. S.D., S.O.Y., D.C., and I.T., performed the experimental work. All authors provided intellectual input and contributed to the preparation of the manuscript. All authors gave final approval of the version to be submitted.

Additional information

Funding

This study was supported by the Gumushane University Scientific Research Foundation (Gumushane, Turkey) under project number 16.F5119.02.02.