Objective:

2

To investigate the effects of asperuloside on cervical cancer based on endoplasmic reticulum (ER) stress and mitochondrial pathway.

Methods:

2

Different doses (12.5–800 μg/mL) of asperuloside were used to treat cervical cancer cell lines Hela and CaSki to calculate the half maximal inhibitory concentration (IC 50 ) of asperuloside. The cell proliferation was analyzed by clone formation assay. Cell apoptosis

intracellular reactive oxygen species (ROS) and mitochondrial membrane potential were determined by flow cytometry. The protein expressions of cleaved-caspase-3

Bcl-2

Bax

Cyt-c

cleaved-caspase-4 and glucose-regulated protein 78 (GRP78) were analyzed by Western blot. And the inhibitor of ER stress

4-phenyl butyric acid (4-PBA) was used to treat cervical cancer cells to further verify the role of ER stress in the apoptosis of cervical cancer cells induced by asperuloside.

Results:

2

Asperuloside of 325

650

and 1300 μg/mL significantly inhibited the proliferation and promoted apoptosis of Hela and CaSki cells (

P

<

0.01). All doses of asperuloside significantly increased intracellular ROS levels

reduced mitochondrial membrane potential

significantly reduced Bcl-2 protein expression level

and increased Bax

Cyt-c

GRP78 and cleaved-caspase-4 expressions (

P

<

0.01). In addition

10 mmol/L 4-PBA treatment significantly promoted cell proliferation and reduced apoptosis (

P

<

0.05)

and 650 μg/mL asperuloside could reverse 4-PBA-induced increased cell proliferation

decreased apoptosis and cleaved-caspase-3

-4 and GRP78 protein expressions (

P

<

0.05).

Conclusion:

2

Our study revealed the role of asperuloside in cervical cancer

suggesting that asperuloside promotes apoptosis of cervical cancer cells through ER stress-mitochondrial pathway.