AI Article Synopsis
- Tumor cells primarily use aerobic glycolysis for energy, with hexokinase 2 (HK2) playing a crucial role, making it a potential target for cancer therapy.
- In colorectal cancer, HK2 expression is significantly higher in tumor tissues compared to adjacent normal tissues, and its levels are linked to cancer progression and patient outcomes.
- The HK2 inhibitor 3-Bromopyruvate (3-BP) effectively reduces colon cancer cell survival and induces apoptosis while also causing endoplasmic reticulum stress, suggesting that targeting both HK2 and stress responses could enhance cancer treatments.
Article Abstract
Compared with normal cells, tumor cells mainly obtain energy through aerobic glycolysis. Hexokinase 2 (HK2) plays a key role in the regulation of tumor cell aerobic glycolysis, and targeting HK2 has become a new strategy for cancer treatment. However, little is known about the role of HK2 in colon cancer and the regulation of its targeted inhibitors. In this study, we found that the expression of HK2 in colorectal cancer tissues was significantly higher than that in adjacent tissues, and the expression level of HK2 in metastatic colorectal cancer was further increased. Meanwhile, the expression level of HK2 was closely related to clinical TNM stage and outcome of colorectal cancer patients. We provide here evidence that HK2 inhibitor 3-Bromopyruvate acid (3-BP) can significantly inhibit the survival and proliferation of colon cancer cells, and induce apoptosis through mitochondrial apoptosis signaling pathway. In addition, we found that 3-BP can also induce endoplasmic reticulum stress in colon cancer cells, the mechanism may be through the increase of intracellular calcium concentration. In vitro and in vivo experiments showed that inhibition of endoplasmic reticulum stress could further increase the proliferation inhibition and apoptosis induced by 3-BP. Collectively, our results show that HK2 is highly expressed in colorectal cancer. 3-BP, an inhibitor of HK2, can induce apoptosis and endoplasmic reticulum stress in colon cancer cells. Endoplasmic reticulum stress plays a protective role in cell death induced by 3-BP. This result suggested that targeting HK2 and endoplasmic reticulum stress may be a valuable strategy in targeted and combination therapy of colon cancer.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9106785 | PMC |
| http://dx.doi.org/10.1007/s12192-022-01267-z | DOI Listing |
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