Natural Compounds Targeting the Autophagy Pathway in the Treatment of Colorectal Cancer

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2023 Apr 28

PMID 37108476

Authors

Yin-Xiao Du

Abdullah Al Mamun

Ai-Ping Lyu

Hong-Jie Zhang

Affiliations

Soon will be listed here.

Abstract

Autophagy is a highly conserved intracellular degradation pathway by which misfolded proteins or damaged organelles are delivered in a double-membrane vacuolar vesicle and finally degraded by lysosomes. The risk of colorectal cancer (CRC) is high, and there is growing evidence that autophagy plays a critical role in regulating the initiation and metastasis of CRC; however, whether autophagy promotes or suppresses tumor progression is still controversial. Many natural compounds have been reported to exert anticancer effects or enhance current clinical therapies by modulating autophagy. Here, we discuss recent advancements in the molecular mechanisms of autophagy in regulating CRC. We also highlight the research on natural compounds that are particularly promising autophagy modulators for CRC treatment with clinical evidence. Overall, this review illustrates the importance of autophagy in CRC and provides perspectives for these natural autophagy regulators as new therapeutic candidates for CRC drug development.

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References

Luo J, Hu Y, Wang H . Ursolic acid inhibits breast cancer growth by inhibiting proliferation, inducing autophagy and apoptosis, and suppressing inflammatory responses via the PI3K/AKT and NF-κB signaling pathways . Exp Ther Med. 2017; 14(4):3623-3631. PMC: 5639319. DOI: 10.3892/etm.2017.4965. View

Huang X, Yang Z, Xie Q, Zhang Z, Zhang H, Ma J . Natural products for treating colorectal cancer: A mechanistic review. Biomed Pharmacother. 2019; 117:109142. DOI: 10.1016/j.biopha.2019.109142. View

Lima C, Pereira-Wilson C, Rattan S . Curcumin induces heme oxygenase-1 in normal human skin fibroblasts through redox signaling: relevance for anti-aging intervention. Mol Nutr Food Res. 2010; 55(3):430-42. DOI: 10.1002/mnfr.201000221. View

Park J, Jung C, Seo M, Otto N, Grunwald D, Kim K . The ULK1 complex mediates MTORC1 signaling to the autophagy initiation machinery via binding and phosphorylating ATG14. Autophagy. 2016; 12(3):547-64. PMC: 4835982. DOI: 10.1080/15548627.2016.1140293. View

Hanada T, Noda N, Satomi Y, Ichimura Y, Fujioka Y, Takao T . The Atg12-Atg5 conjugate has a novel E3-like activity for protein lipidation in autophagy. J Biol Chem. 2007; 282(52):37298-302. DOI: 10.1074/jbc.C700195200. View

Chen H, Huang T, Shieh T, Wu C, Lin L, Hsia S . Isoliquiritigenin Induces Autophagy and Inhibits Ovarian Cancer Cell Growth. Int J Mol Sci. 2017; 18(10). PMC: 5666707. DOI: 10.3390/ijms18102025. View

Bakula D, Muller A, Zuleger T, Takacs Z, Franz-Wachtel M, Thost A . WIPI3 and WIPI4 β-propellers are scaffolds for LKB1-AMPK-TSC signalling circuits in the control of autophagy. Nat Commun. 2017; 8:15637. PMC: 5460038. DOI: 10.1038/ncomms15637. View

de la Cruz-Morcillo M, Valero M, Callejas-Valera J, Arias-Gonzalez L, Melgar-Rojas P, Galan-Moya E . P38MAPK is a major determinant of the balance between apoptosis and autophagy triggered by 5-fluorouracil: implication in resistance. Oncogene. 2011; 31(9):1073-85. DOI: 10.1038/onc.2011.321. View

Feng Q, Liang S, Jia H, Stadlmayr A, Tang L, Lan Z . Gut microbiome development along the colorectal adenoma-carcinoma sequence. Nat Commun. 2015; 6:6528. DOI: 10.1038/ncomms7528. View

10.

Young A, Chan E, Hu X, Kochl R, Crawshaw S, High S . Starvation and ULK1-dependent cycling of mammalian Atg9 between the TGN and endosomes. J Cell Sci. 2006; 119(Pt 18):3888-900. DOI: 10.1242/jcs.03172. View

11.

Orsi A, Razi M, Dooley H, Robinson D, Weston A, Collinson L . Dynamic and transient interactions of Atg9 with autophagosomes, but not membrane integration, are required for autophagy. Mol Biol Cell. 2012; 23(10):1860-73. PMC: 3350551. DOI: 10.1091/mbc.E11-09-0746. View

12.

Devoto L, Celentano V, Cohen R, Khan J, Chand M . Colorectal cancer surgery in the very elderly patient: a systematic review of laparoscopic versus open colorectal resection. Int J Colorectal Dis. 2017; 32(9):1237-1242. DOI: 10.1007/s00384-017-2848-y. View

13.

Winawer S, Fletcher R, Miller L, Godlee F, Stolar M, Mulrow C . Colorectal cancer screening: clinical guidelines and rationale. Gastroenterology. 1997; 112(2):594-642. DOI: 10.1053/gast.1997.v112.agast970594. View

14.

Ouyang L, Shi Z, Zhao S, Wang F, Zhou T, Liu B . Programmed cell death pathways in cancer: a review of apoptosis, autophagy and programmed necrosis. Cell Prolif. 2012; 45(6):487-98. PMC: 6496669. DOI: 10.1111/j.1365-2184.2012.00845.x. View

15.

Gustafsson U, Hausel J, Thorell A, Ljungqvist O, Soop M, Nygren J . Adherence to the enhanced recovery after surgery protocol and outcomes after colorectal cancer surgery. Arch Surg. 2011; 146(5):571-7. DOI: 10.1001/archsurg.2010.309. View

16.

Horita Y, Yamada Y, Kato K, Hirashima Y, Akiyoshi K, Nagashima K . Phase II clinical trial of second-line FOLFIRI plus bevacizumab for patients with metastatic colorectal cancer: AVASIRI trial. Int J Clin Oncol. 2011; 17(6):604-9. DOI: 10.1007/s10147-011-0331-2. View

17.

Zhang P, Lai Z, Chen H, Zhang M, Wang A, Jia T . Curcumin synergizes with 5-fluorouracil by impairing AMPK/ULK1-dependent autophagy, AKT activity and enhancing apoptosis in colon cancer cells with tumor growth inhibition in xenograft mice. J Exp Clin Cancer Res. 2017; 36(1):190. PMC: 5741949. DOI: 10.1186/s13046-017-0661-7. View

18.

Lai K, Killingsworth M, Lee C . The significance of autophagy in colorectal cancer pathogenesis and implications for therapy. J Clin Pathol. 2014; 67(10):854-8. DOI: 10.1136/jclinpath-2014-202529. View

19.

Sasaki K, Tsuno N, Sunami E, Tsurita G, Kawai K, Okaji Y . Chloroquine potentiates the anti-cancer effect of 5-fluorouracil on colon cancer cells. BMC Cancer. 2010; 10:370. PMC: 2914703. DOI: 10.1186/1471-2407-10-370. View

20.

Audisio R, Papamichael D . Treatment of colorectal cancer in older patients. Nat Rev Gastroenterol Hepatol. 2012; 9(12):716-25. DOI: 10.1038/nrgastro.2012.196. View