Role of HSP27 in the multidrug sensitivity and resistance of colon cancer cells

Liu, Zhengyong; Liu, Yi; Long, Yupeng; Liu, Baohua; Wang, Xiangfeng

doi:10.3892/ol.2020.11255

Cited by 13 publications

(9 citation statements)

References 46 publications

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“…Therefore, our present result supports that CC-I induced neuroblastoma cell death is associated with decreased HSP27 and increased p-HSP27 levels. Moreover, HSP27 can directly bind to Akt and increase its phosphorylation (34), and also inhibit apoptosis by the direct interaction and activation of Akt (35). Combined, these observations suggest that the mechanism of CC-I-induced cell death in susceptible neuroblastoma cells is via activation of the HSP27-Akt-JNK pathway.…”

Section: Discussionmentioning

confidence: 90%

Biological Activity of a Thiobarbituric Acid Compound in Neuroblastomas

et al. 2021

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Background/Aim: We have previously reported the identification of the cytotoxic chemotype compound-I (CC-I) from a chemical library screening against glioblastoma. Materials and Methods: The biological activity of CC-I on drug-resistant neuroblastomas [e.g., HFE gene variant C282Y stably transfected human neuroblastoma SH-SY5Y cells (C282Y HFE/SH-SY5Y), SK-N-AS] was characterized using cell culture models and in vivo mouse tumor models. Results: CC-I had potent cytotoxicity on therapy-resistant neuroblastoma cells and limited cytotoxicity on human primary dermal fibroblast cells. In addition, CC-I showed a robust anti-tumor effect on therapyresistant human neuroblastoma C282Y HFE/SH-SY5Y cells but not on SK-N-AS cells in a subcutaneous tumor model. CC-I induced phosphorylation of heat shock protein 27 (HSP27), protein kinase B (Akt), and c-Jun N-terminal kinase (JNK) in C282Y HFE/SH-SY5Y neuroblastoma cells. Conclusion: CC-I may be an effective therapeutic option for therapy-resistant neuroblastomas, especially if they express the C282Y HFE gene variant. Its anti-tumor effects are possibly through HSP27-Akt-JNK activation. Neuroblastoma is the second most common solid tumor discovered in children (1). It begins in the nerve cells outside of the brain, most often in the adrenal glands located on top of both kidneys. Nearly 90% of neuroblastomas are diagnosed by age 10 (2). In the United States, neuroblastoma occurs in about 800 children (age up to 14) each year, which accounts for 6% of all childhood cancers (3). The International Neuroblastoma Risk Group Staging System was developed by the International Neuroblastoma Risk Group for the standardization of neuroblastoma risk classification and for clinical trials (4). Risk factors for neuroblastoma include age at diagnosis, disease stage, tumor histology, and N-myc proto-oncogene protein (MYCN) amplification status (5). Although the 5-year survival rate for low-risk neuroblastoma is 95%, the 5-year survival rate for high-risk neuroblastoma is only 40-50% (3). About half of the neuroblastomas are metastatic at diagnosis, and advanced disease remains difficult to treat successfully despite the aggressive multimodality therapy. Treatment for neuroblastoma usually involves a variety of approaches such as chemotherapy, radiation, surgery, stem cell transplantation, biological agents, and immunotherapy (6, 7). The majority of patients with high-risk neuroblastoma will relapse despite receiving aggressive multimodal therapy, while an additional 10% to 20% will be refractory to induction therapy (8, 9). Because of disease heterogeneity among highrisk cases, subsequent management with salvage chemotherapy can be very challenging. Therefore, developing new treatment agents against neuroblastoma, especially therapy-resistant neuroblastoma, is urgently needed. We previously reported the identification of compound CC-I, a thiobarbituric acid derivative, from the screening of the ChemBridge small molecule library compounds, as an effective agent against drug-resistant glioblasto...

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Section: Discussionmentioning

confidence: 90%

Biological Activity of a Thiobarbituric Acid Compound in Neuroblastomas

et al. 2021

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“…The use of these vinca alkaloids for clinical treatment has been approved by the U.S. department of agriculture (USDA) as far back as 1963 due to their ability to prolong life in cancer patients however, they quickly evolved for use primarily in combination therapies (often with DNA-replication inhibitors) for NSCLC patients 73 , 74 , 75 . Of the issues that have arisen from the use of vincristine and vinblastine, among the most prominent are, unsurprisingly, cases of drug resistance and excess toxicity in patients who are genetically lacking in their the CYP3A family enzymes 76 , 77 , 78 , 79 , 80 . Reports of CYP3A5-deficient Japanese, Kenyan and Turkish patients suffering symptoms of excess drug toxicity from standard dosages of vincristine underline the importance of pharmacogenomic considerations even when using chemotherapies with universal targets and the rate of occurrence in various populations of patients highlights the need for population studies to improve the precision of physician guidelines 77 , 78 .…”

Section: Cytoskeleton-targetingmentioning

confidence: 99%

“…Reports of CYP3A5-deficient Japanese, Kenyan and Turkish patients suffering symptoms of excess drug toxicity from standard dosages of vincristine underline the importance of pharmacogenomic considerations even when using chemotherapies with universal targets and the rate of occurrence in various populations of patients highlights the need for population studies to improve the precision of physician guidelines 77 , 78 . Interestingly, the overexpression of HSP27 is linked to vincristine resistance 79 , 80 . HSP27 is known to inhibit caspase activation, which not only modulates apoptotic pathways but also tubulin cleavage 81 , 82 .…”

Section: Cytoskeleton-targetingmentioning

confidence: 99%

Personalized medicine of non-gene-specific chemotherapies for non-small cell lung cancer

Jiang

Cai

et al. 2021

Acta Pharmaceutica Sinica B

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Non-small cell lung cancer is recognized as the deadliest cancer across the globe. In some areas, it is more common in women than even breast and cervical cancer. Its rise, vaulted by smoking habits and increasing air pollution, has garnered much attention and resource in the medical field. The first lung cancer treatments were developed more than half a century ago. Unfortunately, many of the earlier chemotherapies often did more harm than good, especially when they were used to treat genetically unsuitable patients. With the introduction of personalized medicine, physicians are increasingly aware of when, how, and in whom, to use certain anti-cancer agents. Drugs such as tyrosine kinase inhibitors, anaplastic lymphoma kinase inhibitors, and monoclonal antibodies possess limited utility because they target specific oncogenic mutations, but other drugs that target mechanisms universal to all cancers do not. In this review, we discuss many of these non-oncogene-targeting anti-cancer agents including DNA replication inhibitors ( i . e ., alkylating agents and topoisomerase inhibitors) and cytoskeletal function inhibitors to highlight their application in the setting of personalized medicine as well as their limitations and resistance factors.

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“…Among them, the overexpression of ATP-binding cassette (ABC) transporter [29,30], which function as active drug e ux pumps, is the primary mechanism of drug resistance, leading to decreased intracellular drug accumulation [31,32]. Although several inhibitors of ABC transporter had been investigated, their clinical usage was still limited, due to the uncertain active mechanism and the potential interactions with other chemo-drugs [33][34][35]. Therefore, it is urgent to develop an effective drug delivery system to increase the therapeutic uptake of drugs at the tumor site and potentially reverse the tumor MDR [36].…”

Section: Introductionmentioning

confidence: 99%

Enzyme-Catalyzed Synthesis of Selenium-Doped Manganese Phosphate for Synergistic Therapy of Drug-Resisted Colorectal Tumor

Pei

Liu

et al. 2022

Preprint

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Postoperative chemotherapy for colorectal cancer often causes multidrug resistance (MDR), which seriously affects the therapeutic effect and has been an urgent problem to be solved. Herein, selenium-doped manganese phosphate (Se-MnP) nanoparticles with amorphous structure have been prepared by a bioinspired enzyme-catalyzed strategy, using alkaline phosphatase, fructose disodium diphosphate. Se-MnP have an organic-inorganic hybrid composition, which is assembled from smaller-scale nanoclusters. Se-MnP has showed good Fenton reaction activity in chemodynamic therapy (CDT) due to the presence of manganese ions. Moreover, results from in vitro and in vivo studies demonstrated that Se-MnP as an effective drug carrier of oxaliplatin (OX) can reverse multidrug resistance of colorectal cancer cells and simultaneously induce casparase-mediated apoptosis of colorectal cancer cells. The Se-MnP reverse the MDR of colorectal cancer by down-regulating the expression of MDR-related ABC (ATP binding cassette) transporters proteins (ABCB1 and ABCC1). Finally, the in vivo studies demonstrated that OX-loaded Se-MnP can significantly inhibit OX-resistant HCT116 (HCT116/DR) tumor growth in nude mice. Considering the facile method of preparation and biomimetic chemical properties, the Se-MnP with the multiple functions will be a promising candidate for treating colorectal tumors with MDR characteristics.

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Role of HSP27 in the multidrug sensitivity and resistance of colon cancer cells

Cited by 13 publications

References 46 publications

Biological Activity of a Thiobarbituric Acid Compound in Neuroblastomas

Biological Activity of a Thiobarbituric Acid Compound in Neuroblastomas

Personalized medicine of non-gene-specific chemotherapies for non-small cell lung cancer

Enzyme-Catalyzed Synthesis of Selenium-Doped Manganese Phosphate for Synergistic Therapy of Drug-Resisted Colorectal Tumor

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