Inhibition of Growth of Colon Tumors and Proliferation of HT-29 Cells by Extract Through Mediating G/G Cell Cycle Arrest, Cell Apoptosis, and Intracellular ROS Generation

Overview

Journal Oxid Med Cell Longev

Publisher Wiley

Specialties Cell Biology
Endocrinology

Date 2022 Jan 10

PMID 35003521

Authors

Yongli Zhang

Guilin Chen

Xiaocui Zhuang

Mingquan Guo

Affiliations

Soon will be listed here.

Abstract

Sprague (), widely distributed in Africa, is a traditional medicinal plant used for the treatment of various diseases including cancer. We intended to evaluate the anticolorectal cancer (CRC) activities of the crude extract from (WUD) and reveal the underlying molecular mechanisms of its action. We found that WUD inhibited the proliferation of HT-29 and HCT116 cells in a time- and dose-dependent manner and induced intracellular ROS generation. The inhibitory effect of WUD on the proliferation of HT-29 and HCT116 cells could be attenuated by NAC (a ROS scavenger) in a dose-dependent manner. WUD induced G/G phase arrest, down-regulated the protein expression of Cyclin D1 via ROS accumulation in HT-29 cells. In search of the molecular mechanism involved in WUD-induced Cyclin D1 down-regulation, it was found that WUD can suppress PI3K/Akt/GSK3 signaling pathway in HT-29 cells. Next, it was found that WUD also activated apoptosis, poly-ADP ribose polymerase 1 (PARP1) cleavage and down-regulated pro-caspase 3 in HT-29 and HCT116 cells. Besides, WUD decreased the growth of colon tumors in the xenograft mouse model. We demonstrated for the first time that ROS and their modulation in the corresponding intracellular signaling could play a significant role in the potential activity of WUD against CRC cells.

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References

Russo A, Cardile V, Graziano A, Avola R, Montenegro I, Cuellar M . Antigrowth activity and induction of apoptosis in human melanoma cells by Drymis winteri forst extract and its active components. Chem Biol Interact. 2019; 305:79-85. DOI: 10.1016/j.cbi.2019.03.029. View

Su Q, Brodie P, Liu Y, Miller J, Andrianjafy N, Antsiferana R . Antiproliferative Triterpenoid Saponins from Leptaulus citroides Baill. from the Madagascar Rain Forest. Nat Prod Bioprospect. 2016; 6(1):31-9. PMC: 4749521. DOI: 10.1007/s13659-015-0083-1. View

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

Alao J . The regulation of cyclin D1 degradation: roles in cancer development and the potential for therapeutic invention. Mol Cancer. 2007; 6:24. PMC: 1851974. DOI: 10.1186/1476-4598-6-24. View

Zhang Y, Chen G, Liu Y, Zhuang X, Guo M . Stimulation of ROS Generation by Extract of Leading to G/G Cell Cycle Arrest and Antiproliferation in A549 Cells. Antioxidants (Basel). 2021; 10(10). PMC: 8533466. DOI: 10.3390/antiox10101559. View

Manning B, Toker A . AKT/PKB Signaling: Navigating the Network. Cell. 2017; 169(3):381-405. PMC: 5546324. DOI: 10.1016/j.cell.2017.04.001. View

Xu M, Litaudon M, Krief S, Martin M, Kasenene J, Kiremire B . Ugandenial A, a new drimane-type sesquiterpenoid from Warburgia ugandensis. Molecules. 2009; 14(10):3844-50. PMC: 6255255. DOI: 10.3390/molecules14103844. View

Yuan L, Wei S, Wang J, Liu X . Isoorientin induces apoptosis and autophagy simultaneously by reactive oxygen species (ROS)-related p53, PI3K/Akt, JNK, and p38 signaling pathways in HepG2 cancer cells. J Agric Food Chem. 2014; 62(23):5390-400. DOI: 10.1021/jf500903g. View

Reczek C, Chandel N . ROS Promotes Cancer Cell Survival through Calcium Signaling. Cancer Cell. 2018; 33(6):949-951. DOI: 10.1016/j.ccell.2018.05.010. View

10.

Safe S, Abbruzzese J, Abdelrahim M, Hedrick E . Specificity Protein Transcription Factors and Cancer: Opportunities for Drug Development. Cancer Prev Res (Phila). 2018; 11(7):371-382. DOI: 10.1158/1940-6207.CAPR-17-0407. View

11.

Yang H, Villani R, Wang H, Simpson M, Roberts M, Tang M . The role of cellular reactive oxygen species in cancer chemotherapy. J Exp Clin Cancer Res. 2018; 37(1):266. PMC: 6211502. DOI: 10.1186/s13046-018-0909-x. View

12.

Jutooru I, Guthrie A, Chadalapaka G, Pathi S, Kim K, Burghardt R . Mechanism of action of phenethylisothiocyanate and other reactive oxygen species-inducing anticancer agents. Mol Cell Biol. 2014; 34(13):2382-95. PMC: 4054319. DOI: 10.1128/MCB.01602-13. View

13.

Montenegro I, Tomasoni G, Bosio C, Quinones N, Madrid A, Carrasco H . Study on the cytotoxic activity of drimane sesquiterpenes and nordrimane compounds against cancer cell lines. Molecules. 2014; 19(11):18993-9006. PMC: 6270921. DOI: 10.3390/molecules191118993. View

14.

He D, Slebodnick C, Rakotondraibe L . Bioactive drimane sesquiterpenoids and aromatic glycosides from Cinnamosma fragrans. Bioorg Med Chem Lett. 2017; 27(8):1754-1759. DOI: 10.1016/j.bmcl.2017.02.067. View

15.

Kasiappan R, Jutooru I, Karki K, Hedrick E, Safe S . Benzyl Isothiocyanate (BITC) Induces Reactive Oxygen Species-dependent Repression of STAT3 Protein by Down-regulation of Specificity Proteins in Pancreatic Cancer. J Biol Chem. 2016; 291(53):27122-27133. PMC: 5207142. DOI: 10.1074/jbc.M116.746339. View

16.

Dasari R, De Carvalho A, Medellin D, Middleton K, Hague F, Volmar M . Synthetic and Biological Studies of Sesquiterpene Polygodial: Activity of 9-Epipolygodial against Drug-Resistant Cancer Cells. ChemMedChem. 2015; 10(12):2014-26. PMC: 4831215. DOI: 10.1002/cmdc.201500360. View

17.

Zou Z, Chang H, Li H, Wang S . Induction of reactive oxygen species: an emerging approach for cancer therapy. Apoptosis. 2017; 22(11):1321-1335. DOI: 10.1007/s10495-017-1424-9. View

18.

Wube A, Bucar F, Gibbons S, Asres K, Rattray L, Croft S . Antiprotozoal activity of drimane and coloratane sesquiterpenes towards Trypanosoma brucei rhodesiense and Plasmodium falciparum in vitro. Phytother Res. 2010; 24(10):1468-72. DOI: 10.1002/ptr.3126. View

19.

Rojo de la Vega M, Chapman E, Zhang D . NRF2 and the Hallmarks of Cancer. Cancer Cell. 2018; 34(1):21-43. PMC: 6039250. DOI: 10.1016/j.ccell.2018.03.022. View

20.

Tan B, Huang Y, Lan L, Zhang B, Ye L, Yan W . Bruceine D induces apoptosis in human non-small cell lung cancer cells through regulating JNK pathway. Biomed Pharmacother. 2019; 117:109089. DOI: 10.1016/j.biopha.2019.109089. View