Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Sep;37(9):2121-2132.
doi: 10.1002/tox.23555. Epub 2022 May 7.

Antitumor activity of pachymic acid in cervical cancer through inducing endoplasmic reticulum stress, mitochondrial dysfunction, and activating the AMPK pathway

Ting Yang  1 , Sijuan Tian  1 , Yaohui Wang  1 , Jing Ji  1 , Juan Zhao  1
Affiliations

Antitumor activity of pachymic acid in cervical cancer through inducing endoplasmic reticulum stress, mitochondrial dysfunction, and activating the AMPK pathway

Ting Yang et al. Environ Toxicol. 2022 Sep.

Abstract

Pachymic acid has various pharmacological effects, including anti-inflammatory, antioxidant, immunomodulatory, and antitumor. However, the role of pachymic acid in cervical cancer remains unclear. So, we investigated the effects of pachymic acid in cervical cancer and elucidated the underlying mechanisms. We treated HeLa cells and normal cervical epithelial cells (HUCECs) with pachymic acid (0, 10, 20, 40, 80, or 160 μM) for 72 h, and found the cell activity was decreased in cells treated with 160 μM pachymic acid for 48 h or 80 μM pachymic acid for 72 h, while HUCECs viability without effect. Next, we observed that endoplasmic reticulum (ER) related gene expression, mitochondrial membrane potential (MMP) changes, ATP depletion, reactive oxygen species (ROS) generation and apoptosis were increased. Moreover, we observed that cytochrome C (Cytc) expression was increased and apoptosis-inducing factor (AIF) was decreased in the cytoplasm of pachymic acid-treated HeLa cells. Tauroursodeoxycholic acid (TUDCA) of ER stress inhibitor reversed the effects of pachymic acid on HeLa cells. Phosphorylation of AMPK and acetyl-CoA carboxylase (ACC) of the AMPK pathway key protein was upregulated in pachymic acid-induced HeLa cells. Finally, we subcutaneously implanted HeLa cells into female nude mice and treated them with pachymic acid (50 mg/kg) for 3 weeks (5 days/week), and observed in pachymic acid induced xenograft mice, tumor growth was suppressed, cell apoptosis, ER-related gene expression, and ROS levels in tumor tissues were increased. Therefore, these findings demonstrated that pachymic acid plays an anti-tumor activity in cervical cancer through inducing ER stress, mitochondrial dysfunction, and activating the AMPK pathway.

Keywords: AMPK pathway; ER stress; cervical cancer; mitochondrial dysfunction; pachymic acid.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

References

REFERENCES

    1. Small W Jr, Bacon MA, Bajaj A, et al. Cervical cancer: a global health crisis. Cancer. 2017;123(13):2404-2412.
    1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020;70(1):7-30.
    1. Pimple SA, Mishra GA. Global strategies for cervical cancer prevention and screening. Minerva Ginecol. 2019;71(4):313-320.
    1. Duenas-Gonzalez A, Gonzalez-Fierro A. Pharmacodynamics of current and emerging treatments for cervical cancer. Expert Opin Drug Metab Toxicol. 2019;15(8):671-682.
    1. Akhtar F, Bokhari SRA. Apoptosis. StatPearls. Vol 12. StatPearls Publishing Copyright © 2022, StatPearls Publishing LLC; 2022:925-930.