ROS-Induced DCTPP1 Upregulation Contributes to Cisplatin Resistance in Ovarian Cancer

Overview

Journal Front Mol Biosci

Specialty Biology

Date 2022 Feb 28

PMID 35223993

Authors

Yu Wang

Peishi Chen

Xueping Chen

Daoyuan Gong

Yingsong Wu

Liping Huang

Yao Chen

Affiliations

Soon will be listed here.

Abstract

Cisplatin resistance hinders the improvement of the prognosis of patients with ovarian cancer. Cisplatin induces cancer cell apoptosis by inducing reactive oxygen species (ROS). dCTP pyrophosphatase 1 (DCTPP1) is a newly discovered dNTP pyrophosphatase. This study aimed to identify the role of DCTPP1 in oxidative stress and cisplatin response of ovarian cancer. Our results indicates cisplatin-induced ROS generation was responsible for the upregulation of DCTPP1 in ovarian cancer cells, whereas DCTPP1 knockdown significantly enhanced the sensitivity of ovarian cancer cells to cisplatin, reflect in reactive oxygen species (ROS) generation, double-strand DNA breaks, and cell apoptosis. The expression of redox-related genes and the activation of the PI3/Akt signaling pathway were also inhibited by DCTPP1 knockdown. Our data proposes that the development of therapeutic approaches targeting DCTPP1 may be useful in the treatment of ovarian cancer.

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References

Wang W, Im J, Kim S, Jang S, Han Y, Yang K . ROS-Induced SIRT2 Upregulation Contributes to Cisplatin Sensitivity in Ovarian Cancer. Antioxidants (Basel). 2020; 9(11). PMC: 7698236. DOI: 10.3390/antiox9111137. View

Qiu L, Ma Z, Li X, Deng Y, Duan G, Zhao L . DJ-1 is involved in the multidrug resistance of SGC7901 gastric cancer cells through PTEN/PI3K/Akt/Nrf2 pathway. Acta Biochim Biophys Sin (Shanghai). 2020; 52(11):1202-1214. DOI: 10.1093/abbs/gmaa110. View

Rai P . Human Mut T Homolog 1 (MTH1): a roadblock for the tumor-suppressive effects of oncogenic RAS-induced ROS. Small GTPases. 2012; 3(2):120-5. PMC: 3408976. DOI: 10.4161/sgtp.19556. View

Rai P, Sobol R . Mechanisms of MTH1 inhibition-induced DNA strand breaks: The slippery slope from the oxidized nucleotide pool to genotoxic damage. DNA Repair (Amst). 2019; 77:18-26. PMC: 6478497. DOI: 10.1016/j.dnarep.2019.03.001. View

Kleih M, Bopple K, Dong M, Gaissler A, Heine S, Olayioye M . Direct impact of cisplatin on mitochondria induces ROS production that dictates cell fate of ovarian cancer cells. Cell Death Dis. 2019; 10(11):851. PMC: 6838053. DOI: 10.1038/s41419-019-2081-4. View

Martinez-Arribas B, Requena C, Perez-Moreno G, Ruiz-Perez L, Vidal A, Gonzalez-Pacanowska D . DCTPP1 prevents a mutator phenotype through the modulation of dCTP, dTTP and dUTP pools. Cell Mol Life Sci. 2019; 77(8):1645-1660. PMC: 7162842. DOI: 10.1007/s00018-019-03250-x. View

Girish K, Paul M, Thushara R, Hemshekhar M, Shanmuga Sundaram M, Rangappa K . Melatonin elevates apoptosis in human platelets via ROS mediated mitochondrial damage. Biochem Biophys Res Commun. 2013; 438(1):198-204. DOI: 10.1016/j.bbrc.2013.07.053. View

Requena C, Perez-Moreno G, Ruiz-Perez L, Vidal A, Gonzalez-Pacanowska D . The NTP pyrophosphatase DCTPP1 contributes to the homoeostasis and cleansing of the dNTP pool in human cells. Biochem J. 2014; 459(1):171-80. DOI: 10.1042/BJ20130894. View

Jang H, Lee O, Lee Y, Yoon H, Chang E, Park M . Melatonin prevents cisplatin-induced primordial follicle loss via suppression of PTEN/AKT/FOXO3a pathway activation in the mouse ovary. J Pineal Res. 2016; 60(3):336-47. DOI: 10.1111/jpi.12316. View

10.

Rai P, Young J, Burton D, Giribaldi M, Onder T, Weinberg R . Enhanced elimination of oxidized guanine nucleotides inhibits oncogenic RAS-induced DNA damage and premature senescence. Oncogene. 2010; 30(12):1489-96. DOI: 10.1038/onc.2010.520. View

11.

Bao L, Jaramillo M, Zhang Z, Zheng Y, Yao M, Zhang D . Nrf2 induces cisplatin resistance through activation of autophagy in ovarian carcinoma. Int J Clin Exp Pathol. 2014; 7(4):1502-13. PMC: 4014230. View

12.

Deng X, Lin N, Fu J, Xu L, Luo H, Jin Y . The Nrf2/PGC1 Pathway Regulates Antioxidant and Proteasomal Activity to Alter Cisplatin Sensitivity in Ovarian Cancer. Oxid Med Cell Longev. 2020; 2020:4830418. PMC: 7714579. DOI: 10.1155/2020/4830418. View

13.

Jaramillo M, Zhang D . The emerging role of the Nrf2-Keap1 signaling pathway in cancer. Genes Dev. 2013; 27(20):2179-91. PMC: 3814639. DOI: 10.1101/gad.225680.113. View

14.

Vlahos N, Kalampokas T, Fotiou S . Endometriosis and ovarian cancer: a review. Gynecol Endocrinol. 2009; 26(3):213-9. DOI: 10.1080/09513590903184050. View

15.

Srinivas U, Tan B, Vellayappan B, Jeyasekharan A . ROS and the DNA damage response in cancer. Redox Biol. 2019; 25:101084. PMC: 6859528. DOI: 10.1016/j.redox.2018.101084. View

16.

Preya U, Lee K, Kim N, Lee J, Jang D, Choi J . The natural terthiophene α-terthienylmethanol induces S phase cell cycle arrest of human ovarian cancer cells via the generation of ROS stress. Chem Biol Interact. 2017; 272:72-79. DOI: 10.1016/j.cbi.2017.05.011. View

17.

Lu J, Dong W, He H, Han Z, Zhuo Y, Mo R . Autophagy induced by overexpression of DCTPP1 promotes tumor progression and predicts poor clinical outcome in prostate cancer. Int J Biol Macromol. 2018; 118(Pt A):599-609. DOI: 10.1016/j.ijbiomac.2018.06.005. View

18.

Niu M, Shan M, Liu Y, Song Y, Han J, Sun S . DCTPP1, an Oncogene Regulated by miR-378a-3p, Promotes Proliferation of Breast Cancer via DNA Repair Signaling Pathway. Front Oncol. 2021; 11:641931. PMC: 8185175. DOI: 10.3389/fonc.2021.641931. View

19.

Ghosh S, Dutta N, Banerjee P, Gajbhiye R, Sareng H, Kapse P . Induction of monoamine oxidase A-mediated oxidative stress and impairment of NRF2-antioxidant defence response by polyphenol-rich fraction of Bergenia ligulata sensitizes prostate cancer cells in vitro and in vivo. Free Radic Biol Med. 2021; 172:136-151. DOI: 10.1016/j.freeradbiomed.2021.05.037. View

20.

Wu Y, Huang Y, Chen C, Huang C, Chou C . Comparing PI3K/Akt Inhibitors Used in Ovarian Cancer Treatment. Front Pharmacol. 2020; 11:206. PMC: 7063971. DOI: 10.3389/fphar.2020.00206. View