Curcumin enhances the effects of irinotecan on colorectal cancer cells through the generation of reactive oxygen species and activation of the endoplasmic reticulum stress pathway

Huang, Yanfeng; Zhu, Dajian; Chen, Xiaowu; Chen, Qi-kang; Luo, Zhaoming; Liu, Changchun; Wang, Guoxin; Zhang, Weijie; Liao, Nv-Zhu

doi:10.18632/oncotarget.16828

Cited by 76 publications

(51 citation statements)

References 29 publications

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“…In this study, we also studied the effect of curcumin on intracellular calcium levels and the results showed a significant decrease in the intracellular concentration of Ca 2+ in HepG2 cells of control groups which were elevated after administration of curcumin in a time-dependent manner. These results were in accordance with the results of [41] that suggested that curcumin-induced apoptosis and cell cycle arrest in colorectal cancer cells by increasing intracellular calcium levels. Calcium overload has been shown to play a critical role in the mechanism of initiation and regulation of cell apoptosis.…”

Section: Discussionsupporting

confidence: 93%

The Inhibitory Effect of Curcumin on Ornithine Decarboxylase against Hepatic Carcinoma

Khamis¹,

Sharshar²,

Mahmoud³

et al. 2019

JBM

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Curcumin the active component of turmeric is widely used as an anticancer agent for treating many human cancers. This study aimed at the extraction of curcumin from Curcuma Longa and investigates its therapeutic effect as ornithine decarboxylase (ODC) inhibitor in HepG2 cells. The proliferation of HepG2 cells was carried out by using the MTT assay. In addition, cell cycle analysis was evaluated by using the flow-cytometric technique. Our results showed that curcumin has the ability to inhibit the proliferation of HepG2 cells with IC50 of 24.79 μg/ml and induced G2/M cell cycle arrest. Moreover, it caused an elevation in the intracellular concentration of Ca 2+. Moreover, in the curcumin administration the downregulation expression level of ODC and Bcl-2 genes (p ≤ 0.05) was significant found. On the other hand, upregulation in the expression level of P53, Bax, and caspase-3 genes (p ≤ 0.05). This study concluded that curcumin may be considered as a new saving candidate for the future progress of antitumor agents.

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Section: Discussionsupporting

confidence: 93%

The Inhibitory Effect of Curcumin on Ornithine Decarboxylase against Hepatic Carcinoma

Khamis¹,

Sharshar²,

Mahmoud³

et al. 2019

JBM

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“…In addition, Huang et al reported that curcumin could increase the impacts of irinotecan on CRC cells by effect on cell viability and apoptosis, which is similar to our results [21].…”

Section: Cytotoxic Effects Of Dox In Combination With Curcumin On Hctsupporting

confidence: 92%

Effects of Curcumin in Combination with Doxorubicin in Human Colorectal Cancer Cell Line

Khameneh

Mohammadian²,

Moradi

et al. 2019

Asian Pac J Cancer Biol

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Background: Colorectal cancer (CRC) is one of the main cause of cancer related death worldwide. New therapeutic strategies are required for CRC. Anthracycline drugs such as doxorubicin (DOX) remain one of the most active wide-spectrum and cost-effective drugs in cancer therapy. However, colorectal cancer (CRC) cells are inherently resistant to anthracyclines. Curcumin, the active component and yellow pigment, has been considered as anti-cancer agents with anti-proliferation, anti-invasion, and anti-angiogenesis properties. Previous data show that curcumin may played main role as therapeutic agent for CRC. We aimed to assess the possible sensitizing effects of curcumin in HCT-116 CRC cells treated with DOX.Methods: HCT-116 cells were treated with different doses of curcumin and DOX in increasing concentrations and cytotoxicity were evaluated after 48 h by Water Soluble Tetrazolium Salts(WST-1) method. In double combination treatments (48 h), the mentioned concentration were utilized; D ( Curcumin; 20 μM;DOX;5μM) C (Curcumin; 10 μM;DOX ;2.5μM ), B (Curcumin; 5 μM;DOX;1μM) and A (Curcumin; 2.5 μM;DOX;0.5μM).Results: HCT-116 cells treatments with various concentrations of single agents (DOX and curcumin) decreased the cellular viability in a dose-dependent pattern. Here, we show that treatment of HCT-116 CRC cells with curcumin increases the efficacy of DOX-induced death in HCT-116 cells. Curcumin treatments also results in higher cytotoxicity of DOX and the cell death percent in compared to higher doses in single treatments.Conclusion: It could be concluded that curcumin could acts as chemosensitiser towards the DOX therapy. So it might be used as adjuvant therapy to enhance DOX sensitivity in CRC cells.

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“…As shown by R. Sharma and T. Smith, the ATP content was significantly increased, while glucose (18F-FDG) incorporation was decreased in colorectal cancer cells treated with irinotecan for 72 h (28). In work by Huang et al irinotecan treatment increased ROS generation in two human colorectal cancer cell lines, and this promoted apoptosis and reduced cell viability (29). Irinotecan elevated fatty acid oxidation (FAO) capacity in mouse tissues (liver and muscle) after treatment (30), and this effect was considered to be a common response to the increased energy demands when under genotoxic stress (because FAO provides reducing equivalents-NADH, FADH 2 , for efficient ATP generation via mitochondrial OXPHOS).…”

Section: Discussionmentioning

confidence: 89%

In vivo metabolic and SHG imaging for monitoring of tumor response to chemotherapy

et al. 2018

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Although chemotherapy remains one of the main types of treatment for cancer, treatment failure is a frequent occurrence, emphasizing the need for new approaches to the early assessment of tumor response. The aim of this study was to search for indicators based on optical imaging of cellular metabolism and of collagen in tumors in vivo that enable evaluation of their response to chemotherapy. The study was performed on a mouse colorectal cancer model with the use of cisplatin, paclitaxel, and irinotecan. The metabolic activity of the tumor cells was assessed using fluorescence lifetime imaging of the metabolic cofactor reduced nicotinamide adenine dinucleotide (phosphate), NAD(P)H. Second harmonic generation (SHG) imaging was used to analyze the extent and properties of collagen within the tumors. We detected an early decrease in the free/bound NAD(P)H ratio in all treated tumors, indicating a shift toward a more oxidative metabolism. Monitoring of collagen showed an early increase in the amount of collagen followed by an increase in the extent of its orientation in tumors treated with cisplatin and paclitaxel, and decrease in collagen content in the case of irinotecan. Our study suggests that changes in cellular metabolism and fibrotic stroma organization precede morphological alterations and tumor size reduction, and that this indicates that NAD(P)H and collagen can be considered as intrinsic indicators of the response to treatment. This is the first time that these parameters have been investigated in tumors in vivo in the course of chemotherapy with drugs having different mechanisms of action.COLORECTAL cancer is one of the most common cancers in the world. The current standard treatments for colorectal cancer include surgery, radiation therapy, and chemotherapy. Treatment options and recommendations depend on several factors, such as the type and stage of the cancer, possible side effects, and the patient's preferences and overall health.In standard clinical practice neoadjuvant chemotherapy is used for patients with stage II and III сolorectal cancer to facilitate resection of those tumors that were once considered unresectable. Adjuvant chemotherapy is recommended for Stage III colorectal cancer after resection to prevent tumor recurrence and the development of metastases (1). When resection of all known tumor sites is no longer possible or advisable, palliative care is offered. Current guidelines on the chemotherapy of сolorectal cancer prescribe the use of platinum drugs (oxaliplatin, cisplatin, or similar), or irinotecan in various combinations with a fluoropyrimidine (capecitabine or 5-fluorouracil). Additionally, paclitaxel can be used for chemotherapy of colorectal cancer in combination with 5-fluorouracil.

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Curcumin enhances the effects of irinotecan on colorectal cancer cells through the generation of reactive oxygen species and activation of the endoplasmic reticulum stress pathway

Cited by 76 publications

References 29 publications

The Inhibitory Effect of Curcumin on Ornithine Decarboxylase against Hepatic Carcinoma

The Inhibitory Effect of Curcumin on Ornithine Decarboxylase against Hepatic Carcinoma

Effects of Curcumin in Combination with Doxorubicin in Human Colorectal Cancer Cell Line

In vivo metabolic and SHG imaging for monitoring of tumor response to chemotherapy

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