Oleanolic acid inhibits cervical cancer Hela cell proliferation through modulation of the ACSL4 ferroptosis signaling pathway. 2021

Jiang Xiaofei, and Shi Mingqing, and Sui Miao, and Yuan Yizhen, and Zhang Shuang, and Xia Qinhua, and Zhao Kai
Xuzhou City Hospital of Chinese Medicine, Xuzhou, Jiangsu, 221009, China.

Cervical cancer remains the leading cause of cancerous death among women worldwide. Oleanolic acid (OA) is a substance that occurs naturally in the leaves, fruits, and rhizomes of plants and has anti-cancer activity. In this study, tumor-bearing mice were used as the animal model and Hela cells were used as cellular model. In vivo experiments have showed that OA significantly reduced the size and mass of cervical cancer tumors in mice. In vitro experiments have showed that OA significantly reduced the viability and proliferative capacity of Hela cells. In both in vivo and in vitro assays, OA increased the oxidative stress levels and Fe2+ content, and increased the expression of ferroptosis-related proteins. We found that ACSL4 was highly expressed in both xenograft models and cervical carcinoma cells with OA treatment. Further use of siRNA to interfere with ACSL4 expression in cervical cancer cells revealed that the inhibitory effect of OA on cell viability and proliferative capacity was counteracted, while a decrease in ROS levels and GPX4 was detected, suggesting that OA activated ferroptosis in Hela cells by promoting ACSL4 expression, thereby reducing the survival rate of Hela cells. Therefore, promotion of ACSL4-dependent ferroptosis by OA may be a potential approach for the treatment of cervical cancer.

UI MeSH Term Description Entries
D007501 Iron A metallic element with atomic symbol Fe, atomic number 26, and atomic weight 55.85. It is an essential constituent of HEMOGLOBINS; CYTOCHROMES; and IRON-BINDING PROTEINS. It plays a role in cellular redox reactions and in the transport of OXYGEN. Iron-56,Iron 56
D008297 Male Males
D008807 Mice, Inbred BALB C An inbred strain of mouse that is widely used in IMMUNOLOGY studies and cancer research. BALB C Mice, Inbred,BALB C Mouse, Inbred,Inbred BALB C Mice,Inbred BALB C Mouse,Mice, BALB C,Mouse, BALB C,Mouse, Inbred BALB C,BALB C Mice,BALB C Mouse
D008819 Mice, Nude Mutant mice homozygous for the recessive gene "nude" which fail to develop a thymus. They are useful in tumor studies and studies on immune responses. Athymic Mice,Mice, Athymic,Nude Mice,Mouse, Athymic,Mouse, Nude,Athymic Mouse,Nude Mouse
D009828 Oleanolic Acid A pentacyclic triterpene that occurs widely in many PLANTS as the free acid or the aglycone for many SAPONINS. It is biosynthesized from lupane. It can rearrange to the isomer, ursolic acid, or be oxidized to taraxasterol and amyrin. Oleanol,Hederins,Oleanane Triterpenes,Triterpenes, Oleanane
D002470 Cell Survival The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. Cell Viability,Cell Viabilities,Survival, Cell,Viabilities, Cell,Viability, Cell
D002583 Uterine Cervical Neoplasms Tumors or cancer of the UTERINE CERVIX. Cancer of Cervix,Cancer of the Cervix,Cancer of the Uterine Cervix,Cervical Cancer,Cervical Neoplasms,Cervix Cancer,Cervix Neoplasms,Neoplasms, Cervical,Neoplasms, Cervix,Uterine Cervical Cancer,Cancer, Cervical,Cancer, Cervix,Cancer, Uterine Cervical,Cervical Cancer, Uterine,Cervical Cancers,Cervical Neoplasm,Cervical Neoplasm, Uterine,Cervix Neoplasm,Neoplasm, Cervix,Neoplasm, Uterine Cervical,Uterine Cervical Cancers,Uterine Cervical Neoplasm
D003066 Coenzyme A Ligases Enzymes that catalyze the formation of acyl-CoA derivatives. EC 6.2.1. Acyl CoA Synthetase,Acyl CoA Synthetases,Acyl Coenzyme A Synthetase,Acyl Coenzyme A Synthetases,Coenzyme A Ligase,Coenzyme A Synthetase,Coenzyme A Synthetases,Acid-Thiol Ligases,Co A Ligases,A Ligase, Coenzyme,A Synthetase, Coenzyme,Acid Thiol Ligases,CoA Synthetase, Acyl,CoA Synthetases, Acyl,Ligase, Coenzyme A,Ligases, Acid-Thiol,Ligases, Co A,Ligases, Coenzyme A,Synthetase, Acyl CoA,Synthetase, Coenzyme A,Synthetases, Acyl CoA,Synthetases, Coenzyme A
D005260 Female Females
D006367 HeLa Cells The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for, among other things, VIRUS CULTIVATION and PRECLINICAL DRUG EVALUATION assays. Cell, HeLa,Cells, HeLa,HeLa Cell

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