Mechanistic Study of Macranthoside B Effects on Apoptotic Cell Death in Human Cervical Adenocarcinoma Cells

Li, Y.; Li, M.; Ahmed, K.; Yang, J.; Song, L.; Cui, Zheng-Guo; Hiraku, Yusuke

doi:10.14712/fb2022068050189

Folia Biologica > Archive > 2022, Vol. 68 > Issue 5-6 > Mechanistic Study of Macranthoside B…

Fol. Biol. 2022, 68, 189-200

https://doi.org/10.14712/fb2022068050189

Mechanistic Study of Macranthoside B Effects on Apoptotic Cell Death in Human Cervical Adenocarcinoma Cells

Y. Li¹, M. Li^2,3, K. Ahmed⁴, J. Yang¹, L. Song¹, Zheng-Guo Cui², Yusuke Hiraku²

¹School of Life Science and Technology, Henan Institute of Science and Technology, Xinxiang, China
²Department of Environmental Health, University of Fukui School of Medical Sciences, Fukui, Japan
³School of Medicine, Xizang Minzu University, Weicheng District, Xianyang, Shaanxi, China
⁴Faculty of Eastern Medicine, Hamdard University, Islamabad, Pakistan

Received October 2021
Accepted February 2023

Macranthoside B (MB) is a triterpenoid saponin extracted from Lonicera macranthoides, a traditional Chinese medicine. In the current study, we investigated the anticancer potential of MB in various cancer cells and elucidated its underlying mechanisms. MB exposure inhibited cell proliferation, induced mitochondrial membrane potential (MMP) loss, increased sub-G1 accumulation, and resulted in cleavage of caspase-3 and PARP, which are reflective of apoptosis. In HeLa cells, MB induced down-regulation of SOD2 and GPx1, phosphorylation of Akt and PDK1, and thus promoted ROS-mediated apoptosis. This was further supported by the protection of sub-G1 accumulation, MMP loss, cleavage of caspase-3 and PARP in the presence of N-acetylcysteine (NAC). Additionally, MB induced cell death via down-regulation of ubiquitin-like with PHD and ring-finger domains 1 (UHRF1) and Bcl-xL. Taken together, this study provides a new insight into the apoptosis-inducing potential of MB, and its molecular mechanisms are associated with an increase in oxidative stress and inhibition of the PDK1/Akt pathway.

Keywords

macranthoside B, oxidative stress, Akt/PDK1, antioxidant enzymes, apoptosis.

Funding

This study was supported by Key technologies R&D program of Henan Province (grant No. 202102110166), Key R&D special projects of Henan Province (grant No. 221111110300) and Key scientific and technological projects in Henan Province (grant No. 212102310876).