Curcumenol Targeting YWHAG Inhibits the Pentose Phosphate Pathway and Enhances Antitumor Effects of Cisplatin

Zhijie Mao; Liyan Zhong; Xiaodan Zhuang; Haoen Liu; Yan Peng

doi:10.1155/2022/3988916

Curcumenol Targeting YWHAG Inhibits the Pentose Phosphate Pathway and Enhances Antitumor Effects of Cisplatin

Evid Based Complement Alternat Med. 2022 Jun 26:2022:3988916. doi: 10.1155/2022/3988916. eCollection 2022.

Authors

Zhijie Mao^{1

2

3}, Liyan Zhong^{1

2

3}, Xiaodan Zhuang^{1

2

3}, Haoen Liu^{1

2

3}, Yan Peng^{1

2

3}

Affiliations

¹ ChangZhou Wujin People's Hospital, Changzhou 213017, Jiangsu, China.
² Wujin Hospital Affiliated with Jiangsu University, Changzhou 213017, Jiangsu, China.
³ The Wujin Clinical College of Xuzhou Medical University, Changzhou 213017, Jiangsu, China.

Abstract

Objective: Cervical cancer is a common cancer in women. The drug resistance of chemotherapeutic agents has always been an urgent problem to be solved in clinics. The purpose of this study was to determine the role of tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein gamma polypeptide (YWHAG) in cervical cancer and explore the effect of Curcuma on cervical cancer and its possible mechanism.

Methods: YWHAG expression in cervical cancer was confirmed using The Cancer Genome Atlas (TCGA) database. Then, the effects of YWHAG on the proliferation and invasion of HeLa and C33A cervical cancer cells were detected by the cell counting kit-8 (CCK-8) and transwell assay. The relationship between YWHAG and the pentose phosphorylation pathway was further studied. CCK-8, Edu, and quantitative real-time polymerase chain reaction were used to confirm that Curcuma inhibited the sensitivity of YWHAG to cisplatin chemotherapy and to detect the expression of apoptosis-related proteins.

Results: YWHAG was highly expressed in cervical cancer and was associated with poor prognosis. The proliferation and invasion abilities of HeLa and C33A cells decreased after YWHAG knockout. The TCGA database of cervical cancer showed a positive correlation between YWHAG and hypoxia-inducible factor-1 subunit alpha (HIF-1α) expression. YWHAG expression increased with HIF-1α overexpression. YWHAG knockdown reduced the protein expression in the pentose phosphorylation pathway. Curcumenol inhibited YWHAG expression. Compared with cisplatin alone, curcumenol combined with cisplatin can reduce cell proliferation and invasion and reduce matrix metalloproteinase (MMP) 2 and MMP9 expression. It can also increase apoptosis, decrease B cell lymphoma 2 (Bcl-2) expression, and increase the expression of Bcl-2 antagonist X, caspase-3, and polyadenosine diphosphate-ribose polymerase.

Conclusion: YWHAG can interact with HIF-1α to affect the proliferation and invasion of cervical cancer cells. YWHAG knockout can reduce the expression of pentose phosphorylation pathway-related proteins. Curcumenol can enhance cisplatin to inhibit cancer cell proliferation, migration, and invasion and promote tumor cell apoptosis. The combination of drugs may promote the apoptosis of cervical cancer cells through the YWHAG pathway.