Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2023 Aug 24:14:1257450.
doi: 10.3389/fphar.2023.1257450. eCollection 2023.

Phytochemicals targeting glycolysis in colorectal cancer therapy: effects and mechanisms of action

Lu Zhan #  1 , Fangting Su #  1 , Qiang Li #  1 , Yueqiang Wen  2 , Feng Wei  1 , Zhelin He  3 , Xiaoyan Chen  3 , Xiang Yin  3 , Jian Wang  3 , Yilin Cai  1 , Yuxia Gong  1 , Yu Chen  1 , Xiao Ma  4 , Jinhao Zeng  5   6
Affiliations
Review

Phytochemicals targeting glycolysis in colorectal cancer therapy: effects and mechanisms of action

Lu Zhan et al. Front Pharmacol. .

Abstract

Colorectal cancer (CRC) is the third most common malignant tumor in the world, and it is prone to recurrence and metastasis during treatment. Aerobic glycolysis is one of the main characteristics of tumor cell metabolism in CRC. Tumor cells rely on glycolysis to rapidly consume glucose and to obtain more lactate and intermediate macromolecular products so as to maintain growth and proliferation. The regulation of the CRC glycolysis pathway is closely associated with several signal transduction pathways and transcription factors including phosphatidylinositol 3-kinases/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR), adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK), hypoxia-inducible factor-1 (HIF-1), myc, and p53. Targeting the glycolytic pathway has become one of the key research aspects in CRC therapy. Many phytochemicals were shown to exert anti-CRC activity by targeting the glycolytic pathway. Here, we review the effects and mechanisms of phytochemicals on CRC glycolytic pathways, providing a new method of drug development.

Keywords: colorectal cancer; glycolysis; molecular pathways; phytochemicals; warburg effect.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Glycolysis in colorectal cancer cells and the related regulatory pathways. Abbreviation: GLUTs, Glucose transporters; HKs, Hexokinases; PFK1, Phosphofructokinase-1; PK, Pyruvate kinase; LDH, Lactate dehydrogenase; PDK, Pyruvate dehydrogenase kinase; PDH, Pyruvate dehydrogenase; AMPK, Adenosine 5′-monophosphate-activated protein kinase; TSC1/2, Tuberous sclerosis complex1/2; AKT, Protein kinase B; mTOR, Mammalian target of rapamycin; HIF-1, Hypoxia-inducible factor-1; PI3K, Phosphatidylinositol 3-kinases; PTEN, Phosphatase and tensin homolog; USP13, Ubiquitin-specific peptidase 13; RPS7, ribosomal protein S7; TCA, Tricarboxylic acid; PPP, Pentose phosphate pathway; HSP90, Heat shock protein 90; MCTs, Monocarboxylic acid transporters; MEG3, lncRNA maternally expressed gene 3; SOD2, Superoxide dismutase 2.
FIGURE 2
FIGURE 2
Phytochemicals targeting glycolysis in colorectal cancer. Abbreviation: HKs, Hexokinases; PFK1, Phosphofructokinase-1; PK, Pyruvate kinase; LDH, Lactate dehydrogenase; MCTs, Monocarboxylic acid transporters; PDH, Pyruvate dehydrogenase; TCA, Tricarboxylic acid; IL-6, Interleukin 6; SIRT3, Sirtuin-3; JAK2/STAT3, Janus kinase 2/signal transducer and activator of transcription 3; PI3K, Phosphatidylinositol 3-kinases; AKT, Protein kinase B; HIF-1, Hypoxia-inducible factor-1; AMPK, Adenosine 5′-monophosphate-activated protein kinase; hnRNPA1, Heterogeneous nuclear ribonucleoprotein A1; PTBP1, polypyrimidine tract-binding protein 1; PTEN, Phosphatase and tensin homolog.
FIGURE 3
FIGURE 3
Structural formulae of the phytochemicals.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Abdullah N. A., Md Hashim N. F., Ammar A., Muhamad Zakuan N. (2021). An insight into the anti-angiogenic and anti-metastatic effects of oridonin: current knowledge and future potential. Molecules 26 (4), 775. 10.3390/molecules26040775 - DOI - PMC - PubMed
    1. Achi I. T., Sarbadhikary P., George B. P., Abrahamse H. (2022). Multi-target potential of berberine as an antineoplastic and antimetastatic agent: a special focus on lung cancer treatment. Cells 11 (21), 3433. 10.3390/cells11213433 - DOI - PMC - PubMed
    1. Akbarialiabad H., Dahroud M. D., Khazaei M. M., Razmeh S., Zarshenas M. M. (2021). Green tea, A medicinal food with promising neurological benefits. Curr. Neuropharmacol. 19 (3), 349–359. 10.2174/1570159x18666200529152625 - DOI - PMC - PubMed
    1. An J., Ha E. M. (2022). Extracellular vesicles derived from Lactobacillus plantarum restore chemosensitivity through the PDK2-mediated glucose metabolic pathway in 5-FU-resistant colorectal cancer cells. J. Microbiol. 60 (7), 735–745. 10.1007/s12275-022-2201-1 - DOI - PubMed
    1. Ancey P. B., Contat C., Meylan E. (2018). Glucose transporters in cancer - from tumor cells to the tumor microenvironment. Febs J. 285 (16), 2926–2943. 10.1111/febs.14577 - DOI - PubMed

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the Program of Science and Technology Department of Sichuan Province (Grant Nos. 2023YFS0476, 2023YFQ0016, and 2023NSFSC0039), the Project of Traditional Chinese Medicine Administration of Sichuan Province (Grant Nos.MS461), “Hundred Talents Program” of the Hospital of the Chengdu University of Traditional Chinese Medicine (Grant Nos. 20-Q03 and 22-B09), Xinglin Scholar Research Promotion Project of Chengdu University of TCM (Grant Nos. QJJJ2022010 and QJRC2022028).
-