Targeting the tumor microenvironment as a potential therapeutic approach in colorectal cancer: Rational and progress

Bahrami, Afsane; Khazaei, Majid; Hassanian, Seyed Mahdi; Shahidsales, Soodabeh; Joudi‐Mashhad, Mona; Maftouh, Mina; Jazayeri, Mir Hadi; Parizade, Mohammad Reza; Ferns, Gordon A.; Rezayi, Majid

doi:10.1002/jcp.26041

Cited by 42 publications

(27 citation statements)

References 83 publications

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“…Colorectal cancer (CRC) is the third most common type of cancer and fourth leading cause of cancer death in the world as about 690,000 people annually die for this disease (Arnold et al, 2017). Clinically, chemotherapy and radiation are commonly used before or after surgery, even so 40% of all patients develop metastasis and presented recidives (Bahrami et al, 2018). CRC is classified by its clinicopathological characteristics, but clinical outcomes and drugs response, molecular characteristics and prognosis are uncertain and heterogeneous (Rodriguez-Salas et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Apoptosis induction by Pleurotus sajor-caju (Fr.) Singer extracts on colorectal cancer cell lines

Finimundy

Abreu

Bonetto

et al. 2018

Food and Chemical Toxicology

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Pleurotus sajor-caju (PSC) is an edible mushroom used in food supplements, presenting antitumor properties through induction of cell death pathways. The PSC potential against colorectal cancer was analyzed by exposing HCT116 cells to different PSC extracts. The PSC n-hexane extract (PSC-hex) showed the highest cytotoxicity effect (IC value 0.05 mg/mL). The observed cytotoxicity was then associated to apoptosis-promoting and cell cycle-arrest pathways. PSC-hex was able to induce apoptosis related to breakdown of mitochondrial membrane potential and ROS generation. The absence of cytotoxicity in HTC116 and HTC116 cells, alongside with an increase in p53, Bax and Caspase-3 expression, and decrease in Bcl-2 expression, supports that the pro-apoptotic effect is probably induced through a p53 associated pathway. PSC-hex induced cell cycle arrest at G2/M in HCT116 without cytotoxicity in HTC116 cells. These findings suggest that a p21/p53 cell cycle regulation pathway is probably disrupted by compounds present on PSC-hex. Identification of the major components was then performed with ergosta-5,7,22-trien-3β-ol representing 30.6% of total weight. In silico docking studies of ergosta-5,7,22-trien-3β against Bcl-2 were performed and results show a credible interaction with the Bcl-2 hydrophobic cleft. The results show that PSC-hex can be used as supplementary food for adjuvant therapy in colorectal carcinoma.

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Section: Introductionmentioning

confidence: 99%

Apoptosis induction by Pleurotus sajor-caju (Fr.) Singer extracts on colorectal cancer cell lines

Finimundy

Abreu

Bonetto

et al. 2018

Food and Chemical Toxicology

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“…These are the 6 hallmarks of malignancy. 13 In association with CD 26 with dipeptidyl peptidase IV activity, ADA exists on the cell surface and intracellularly as well, without own transmembrane domain. 14 Solid tumors release adenosine due to adenine nucleotide degradation which is caused by severe hypoxia and necrosis which in turn is caused by aggressive growth of the tumor.…”

Section: Discussionmentioning

confidence: 99%

“…13.63%) patients were in stage I, 31 (35.22%) patients in stage II, 27 (30.68%) patients in stage III and 9 (10.22%) patients in stage IV of the disease. Mean ADA levels in stage I, II, III and IV were found to be 23.88 IU/l, 27.68 IU/l, 30.50 IU/l and 41.88 IU/l respectively, which are statistically significant for respective stage of the malignancy.…”

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confidence: 97%

Study of serum adenosine deaminase levels in head and neck malignancies

Rao

Reshma

2020

Int J Otorhinolaryngol Head Neck Surg

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Background: Head and neck malignancies are the malignancies occurring at various sites like scalp, ear, nose and paranasal sinuses, nasopharynx, oral cavity, oropharynx, hypopharynx, larynx, and salivary glands. There are various biomarkers which aid in early diagnosis and management of head and neck malignancies. In order to study various parameters aiding in early diagnosis, this study has been taken up to estimate serum adenosine deaminase levels among these patients.Methods: Eighty-eight clinically diagnosed head and neck malignancy patients of both genders were included in this study on simple random basis. After obtaining the written informed consent from the patient, a peripheral venous sample of blood was taken and serum ADA levels were estimated. Data was analyzed using IBM SPSS Version 22.Results: Serum ADA levels are found to be statistically significant with respect to various stages of head and neck malignancies including malignancy of unknown origin. Mean ADA level in this study was 30.33 IU/l. Mean ADA levels in MUO, primary tumor with neck secondaries were 37 IU/l, 38.7 IU/l respectively. Mean ADA levels in patients with primary tumor without neck secondaries was 27.9 IU/l.Conclusions: The Serum ADA levels among head and neck malignancy patients including MUO is a simple, inexpensive diagnostic biomarker enzyme which is easy and rapid to estimate. This study emphasizes on using Serum ADA levels as a prognostic indicator among head and neck malignancies who are on various modalities of treatment.

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“…As the 'residence niche' of cancer cells, the composition and structure of the tumor microenvironment not only affects the bio-behavior, but also determines the survival and elimination of tumor cells (1)(2)(3). Targeting the tumor microenvironment by remodeling its components and construction could be a useful a strategy to treat and prevent cancer (4).…”

Section: Introductionmentioning

confidence: 99%

Protein kinase D1 regulates hypoxic metabolism through HIF-1α and glycolytic enzymes incancer cells

et al. 2018

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Protein kinase D1 (PKD1), one of the protein kinase D (PKD) family members, plays a prominent role in multiple bio-behaviors of cancer cells. Low pH and hypoxia are unique characteristics of the tumor microenvironment. The aim of this study was to investigate the role and mechanism of PKD1 in regulating metabolism in the human tongue squamous cell carcinoma (TSCC) cell line SCC25 under a hypoxic condition, as well as growth and apoptosis. Here, we found that hypoxia not only induced the expression of HIF-1α, but also induced the expression and activation of PKD1. Moreover, we inhibited the expression of PKD1 by shRNA interference, and the growth of SCC25 cells under hypoxia was significantly decreased, as well as the expression of HIF-1α, while the percentage of apoptotic SCC25 cells was increased. Furthermore, stable silencing of PKD1 in SCC25 cells under a hypoxic condition decreased glucose uptake, lactate production and glycolytic enzyme (GLUT-1 and LDHA) expression, as well as reduced the phosphorylation of p38 MAPK. The results revealed that following inhibition of the expression of PKD1 under a hypoxic condition, the growth and metabolism of the SCC25 cells were significantly suppressed. In contrast, when PKD1 was overexpressed in SCC25 cells, the results were completely reversed, except for growth and apoptosis. Taken together, our results demonstrated that PKD1 not only regulates the hypoxic glycolytic metabolism of cancer cells via regulation of the expression of HIF-1α and glycolytic enzymes, but is also involved in the remodeling of the acidic tumor microenvironment. This study suggests that PKD1 may be a potential target for microenvironment-directed tumor biotherapy.

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Targeting the tumor microenvironment as a potential therapeutic approach in colorectal cancer: Rational and progress

Cited by 42 publications

References 83 publications

Apoptosis induction by Pleurotus sajor-caju (Fr.) Singer extracts on colorectal cancer cell lines

Apoptosis induction by Pleurotus sajor-caju (Fr.) Singer extracts on colorectal cancer cell lines

Study of serum adenosine deaminase levels in head and neck malignancies

Protein kinase D1 regulates hypoxic metabolism through HIF-1α and glycolytic enzymes incancer cells

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