Betulinic Acid Induces ROS-Dependent Apoptosis and S-Phase Arrest by Inhibiting the NF-κB Pathway in Human Multiple Myeloma
Joint Authors
Hu, Yiqiang
Shen, Min
Yang, Yan
Wang, Lanlan
Yang, Xin
Wang, Bo
Huang, Mei
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2019, Issue 2019 (31 Dec. 2019), pp.1-14, 14 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2019-06-09
Country of Publication
Egypt
No. of Pages
14
Main Subjects
Abstract EN
Betulinic acid (BA), as a prospective natural compound, shows outstanding antitumor bioactivities against many solid malignancies.
However, its mechanism against multiple myeloma (MM) remains elusive.
Herein, for the first time, we studied the antitumor activity of BA against MM both in vivo and in vitro.
We showed that BA mediated cytotoxicity in MM cells through apoptosis, S-phase arrest, mitochondrial membrane potential (MMP) collapse, and overwhelming reactive oxygen species (ROS) accumulation.
Moreover, when the ROS scavenger N-acetyl cysteine (NAC) effectively abated elevated ROS, the BA-induced apoptosis was partially reversed.
Our results revealed that BA-mediated ROS overproduction played a pivotal role in anticancer activity.
Molecularly, we found that BA resulted in marked inhibition of the aberrantly activated NF-κB pathway in MM.
As demonstrated by using the NF-κB pathway-specific activator TNF-α and the inhibitor BAY 11-7082, BA-mediated inhibition of the NF-κB pathway directly promoted the overproduction of ROS and, ultimately, cell death.
Furthermore, BA also exerted enormous tumor-inhibitory effects via repressing proliferation and inhibiting the NF-κB pathway in our xenograft model.
Overall, by blocking the NF-κB pathway that breaks redox homeostasis, BA, as a potent NF-κB inhibitor, is a promising therapeutic alternative for MM.
American Psychological Association (APA)
Shen, Min& Hu, Yiqiang& Yang, Yan& Wang, Lanlan& Yang, Xin& Wang, Bo…[et al.]. 2019. Betulinic Acid Induces ROS-Dependent Apoptosis and S-Phase Arrest by Inhibiting the NF-κB Pathway in Human Multiple Myeloma. Oxidative Medicine and Cellular Longevity،Vol. 2019, no. 2019, pp.1-14.
https://search.emarefa.net/detail/BIM-1203929
Modern Language Association (MLA)
Shen, Min…[et al.]. Betulinic Acid Induces ROS-Dependent Apoptosis and S-Phase Arrest by Inhibiting the NF-κB Pathway in Human Multiple Myeloma. Oxidative Medicine and Cellular Longevity No. 2019 (2019), pp.1-14.
https://search.emarefa.net/detail/BIM-1203929
American Medical Association (AMA)
Shen, Min& Hu, Yiqiang& Yang, Yan& Wang, Lanlan& Yang, Xin& Wang, Bo…[et al.]. Betulinic Acid Induces ROS-Dependent Apoptosis and S-Phase Arrest by Inhibiting the NF-κB Pathway in Human Multiple Myeloma. Oxidative Medicine and Cellular Longevity. 2019. Vol. 2019, no. 2019, pp.1-14.
https://search.emarefa.net/detail/BIM-1203929
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1203929