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Targeting of Aerobic Glycolysis: An Emerging Therapeutic Approach Against Colon Cancer

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Colon Cancer Diagnosis and Therapy

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Abstract

Colon cancer is one of the leading causes of cancer-associated deaths in men as well as in women worldwide. Therefore, various researches are being conducted to identify suitable therapeutic targets for designing the safer and effective therapeutic regimens against colon cancer. In view of this, aerobic glycolysis has been identified as one of the prominent and potential therapeutic targets for the treatment of colon cancer. Interestingly, overwhelming reports suggest that not the oxidative phosphorylation (OXPHOS) but rather glycolysis is one of the major sources of energy production in colon cancer even in the presence of sufficient oxygen. Hence, the “Warburg effect” or “aerobic glycolysis” is among the most detectable features in colon cancer which directly or indirectly mediates other hallmark features. This metabolic switch benefits colon cancer in several ways with respect to its development and progression, which include promotion of macromolecular synthesis, evasion of apoptosis, drug resistance, and immunosuppression. In colon cancer, mutations in Wnt, p53, and Ras play a critical role in switching the glucose metabolism from mitochondrial oxidative phosphorylation to cytoplasmic glycolysis. Overall, targeting of aerobic glycolysis by synthetic or natural compounds may help in designing the novel therapeutic approaches for the treatment of colon cancer.

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Abbreviations

3-BrPA:

3-Bromopyruvate

ABCB1:

ATP-binding cassette, subfamily B, member 1

AMPK:

5′ adenosine monophosphate-activated protein kinase

APC:

Adenomatous polyposis coli

AT-1:

Atractylenolide 1

BRAF:

B-Raf

CRC:

Colorectal cancer

CSN:

COP9 signalosome complex subunit 5

DCA:

Dichloroacetate

GIST:

Gastrointestinal stromal tumors

GLUTs:

Glucose transporters

KRAS:

Kirsten rat sarcoma viral oncogene homolog

LDHA:

Lactate dehydrogenase A

LPA:

Lysophosphatidic acid

MIF:

Macrophage migration inhibitory factor

NADPH:

Nicotinamide adenine dinucleotide phosphate

PDH:

Pyruvate dehydrogenase

PDK:

Pyruvate dehydrogenase kinase

PDP:

Pyruvate dehydrogenase phosphatase

PFK:

Phosphofructokinase

PHLPP:

pH domain leucine-rich repeat protein phosphatase

PK:

Pyruvate kinase

PPP:

Pentose phosphate pathway

SGLT:

Sodium-dependent glucose cotransporters

TGF-β:

Tumor growth factor-β

TME:

Tumor microenvironment

TRPC5:

Transient receptor potential canonical channel 5

VEGF-A:

Vascular endothelial growth factor A

α-CHC:

α-Cyano-4-hydroxycinnamate

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Acknowledgment

We thankfully acknowledge fellowship support to Pradip Kumar Jaiswara [Award No. 1002/(SC)(CSIR-UGC NET DEC. 2016], Vishal Kumar Gupta [Award No. 1044/(CSIR-UGC NET JUNE 2019], and Shiv Govind Rawat [Award No. 09/013(0772/2018-EMR-I)] from CSIR, New Delhi. The fellowship supports to Rajan Kumar Tiwari [Award No. R/Dev/IX-Sch.(SRF-JRF-CAS-Zoology)/75159] from the University Grants Commission-Career Advancement Scheme (UGC-CAS) and Pratishtha Sonker [Award No. F117.1/201516/RGNF201517SCUTT4822/(SAIII/Website)] from the University Grants Commission (UGC), New Delhi, are highly acknowledged. Funding from the University Grants Commission and Department of Science & Technology, New Delhi, India, in the form of UGC Start-Up Research Grant (F. No. 30-370/2017 (BSR)) and Early Career Research Award (ECR/2016/001117) is highly acknowledged. Financial support from the Interdisciplinary School of Life Sciences (ISLS) and University Grants Commission-Universities with Potential for Excellence (UGC-UPE), Banaras Hindu University, is also acknowledged. We also acknowledge UGC-CAS and the DST-FIST program to the Department of Zoology, Banaras Hindu University, India.

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  1. Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi, Uttar Pradesh, India

    Pradip Kumar Jaiswara, Vishal Kumar Gupta, Shiv Govind Rawat, Rajan Kumar Tiwari, Pratishtha Sonker & Ajay Kumar

  2. Department of Ophthalmology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India

    Rajendra Prakash Maurya

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  1. Pradip Kumar Jaiswara
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  1. Department of Biotechnology, Guru Ghasidas Vishwavidyalaya, Bilaspur, India

    Naveen Kumar Vishvakarma

  2. Department of Hematology and Medical Oncology, Emory University, Atlanta, GA, USA

    Ganji Purnachandra Nagaraju

  3. Department of Biotechnology, Guru Ghasidas Vishwavidyalaya, Bilaspur, India

    Dhananjay Shukla

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Jaiswara, P.K. et al. (2021). Targeting of Aerobic Glycolysis: An Emerging Therapeutic Approach Against Colon Cancer. In: Vishvakarma, N.K., Nagaraju, G.P., Shukla, D. (eds) Colon Cancer Diagnosis and Therapy. Springer, Cham. https://doi.org/10.1007/978-3-030-64668-4_11

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