Curcumin Chemosensitizes 5-Fluorouracil Resistant MMR-Deficient Human Colon Cancer Cells in High Density Cultures

Shakibaei, Mehdi; Buhrmann, Constanze; Kraehe, Patricia; Shayan, Parviz; Lueders, Cora; Goel, Ajay

doi:10.1371/journal.pone.0085397

Cited by 115 publications

(77 citation statements)

References 54 publications

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“…Thereby, it modulates a large range of intracellular signalling pathways, including PI3K/Akt, Wnt/β-catenin, JAK/STAT, p53 and NF-κB pathway [19,49]. Additionally, it has been previously shown that curcumin enhances the chemosensitivity of CRC to chemotherapeutics through regulation of MiR-34a and MiR-27a, activation of the MMR-repair system, influencing tumor-microenvironment cross-talk and suppression of NF-κB pathway activation [35,[51][52][53][54]. This underlines that specific suppression of tumor-enhancing TNF-β stimulation not only bears the potential of Calebin A for suppressing CRC proliferation alone, but in combination with other natural substances as well, for even better results.…”

Section: Discussionmentioning

confidence: 99%

Evidence That Calebin A, a Component of Curcuma Longa Suppresses NF-κB Mediated Proliferation, Invasion and Metastasis of Human Colorectal Cancer Induced by TNF-β (Lymphotoxin)

et al. 2019

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Objective: Natural polyphenol Calebin A has been recently discovered as a novel derivate from turmeric with anti-cancer potential. Pro-inflammatory cytokine TNF-β (lymphotoxin α) is a stimulant for cancer cell malignity via activation of NF-κB pathway, also in colorectal cancer (CRC). Here, we investigated the potential of Calebin A to suppress TNF-β-induced NF-κB signalling in CRC. Materials and Methods: Three distinct CRC cell lines (HCT116, RKO, SW480) were treated in monolayer or 3-dimensional alginate culture with TNF-β, Calebin A, curcumin, BMS-345541, dithiothreitol (DTT) or antisense oligonucleotides-(ASO) against NF-κB. Results: Calebin A suppressed dose-dependent TNF-β-induced CRC cell vitality and proliferation in monolayer culture. Further, in alginate culture, Calebin A significantly suppressed TNF-β-enhanced colonosphere development, as well as invasion and colony formation of all three CRC cell lines investigated. Calebin A specifically blocked TNF-β-induced activation and nuclear translocation of p65-NF-κB, similar to curcumin (natural NF-κB inhibitor), BMS-345541 (specific IKK inhibitor) and ASO-NF-κB. Moreover, Immunofluorescence and Immunoblotting showed that Calebin A, similar to curcumin or BMS-345541 suppressed TNF-β-induced activation and nuclear translocation of p65-NF-κB and the transcription of NF-κB-promoted biomarkers associated with proliferation, migration and apoptosis, in a doseand time-dependent manner. Those findings were potentiated by the specific treatment of extracted nuclei with DTT, which abrogated Calebin A-mediated nuclear p65-NF-κB-inhibition and restored p65-NF-κB-activity in the nucleus. Conclusion: Overall, these results demonstrate, for the first time, that multitargeted Calebin A has an anti-cancer capability on TNF-β-induced malignities through inhibitory targeting of NF-κB activation in the cytoplasm, as well as by suppressing the binding of p65-NF-κB to DNA.

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Section: Discussionmentioning

confidence: 99%

Evidence That Calebin A, a Component of Curcuma Longa Suppresses NF-κB Mediated Proliferation, Invasion and Metastasis of Human Colorectal Cancer Induced by TNF-β (Lymphotoxin)

et al. 2019

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“…Additional attributes that curcumin offers are its capacity to confer properties of electron receptors which destabilize reactive oxygen species (ROS), therefore explaining its antioxidant and anti-cell death (necrotic, apoptotic or aponecrotic) effects. Curcumin also boosts the sensitization of cancer cells to chemotherapy without exercising additional side effects, a provocative area for continued investigations [56].…”

Section: Health Promotion and Therapeutic Applicationsmentioning

confidence: 99%

Highly Bioavailable Forms of Curcumin and Promising Avenues for Curcumin-Based Research and Application: A Review

et al. 2020

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Curcumin exerts a wide range of beneficial physiological and pharmacological activities, including antioxidant, anti-amyloid, anti-inflammatory, anti-microbial, anti-neoplastic, immune-modulating, metabolism regulating, anti-depressant, neuroprotective and tissue protective effects. However, its poor solubility and poor absorption in the free form in the gastrointestinal tract and its rapid biotransformation to inactive metabolites greatly limit its utility as a health-promoting agent and dietary supplement. Recent advances in micro- and nano-formulations of curcumin with greatly enhanced absorption resulting in desirable blood levels of the active forms of curcumin now make it possible to address a wide range of potential applications, including pain management, and as tissue protective. Using these forms of highly bioavailable curcumin now enable a broad spectrum of appropriate studies to be conducted. This review discusses the formulations designed to enhance bioavailability, metabolism of curcumin, relationships between solubility and particle size relative to bioavailability, human pharmacokinetic studies involving formulated curcumin products, the widely used but inappropriate practice of hydrolyzing plasma samples for quantification of blood curcumin, current applications of curcumin and its metabolites and promising directions for health maintenance and applications.

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“…Combined treatment of curcumin and 5-FU in chemoresistant colorectal cancer cells mediated apoptosis of resistant cells (Figure 1). 55 Curcumin-mediated chemosensitization was shown to be effective through the upregulation of miRNA that induced the suppression of EMT in 5-FU-resistant colorectal cancer cells 56. Experiments conducted on intestinal tumors in C57BL/6J-Min/+ (Min/+) mice showed that curcumin is capable of regulating lymphocyte-mediated immune function 57.…”

Section: Curcumin As a Combinatorial Therapy In Various Cancer Typesmentioning

confidence: 99%

New insights into therapeutic activity and anticancer properties of curcumin

Panda¹,

Chakraborty²,

Sarkar³

et al. 2017

JEP

167

105

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Natural compounds obtained from plants are capable of garnering considerable attention from the scientific community, primarily due to their ability to check and prevent the onset and progress of cancer. These natural compounds are primarily used due to their nontoxic nature and the fewer side effects they cause compared to chemotherapeutic drugs. Furthermore, such natural products perform even better when given as an adjuvant along with traditional chemotherapeutic drugs, thereby enhancing the potential of chemotherapeutics and simultaneously reducing their undesired side effects. Curcumin, a naturally occurring polyphenol compound found in the plant Curcuma longa, is used as an Indian spice. It regulates not only the various pathways of the immune system, cell cycle checkpoints, apoptosis, and antioxidant response but also numerous intracellular targets, including pathways and protein molecules controlling tumor progression. Many recent studies conducted by major research groups around the globe suggest the use of curcumin as a chemopreventive adjuvant molecule to maximize and minimize the desired effects and side effects of chemotherapeutic drugs. However, low bioavailability of a curcumin molecule is the primary challenge encountered in adjuvant therapy. This review explores different therapeutic interactions of curcumin along with its targeted pathways and molecules that are involved in the regulation of onset and progression of different types of cancers, cancer treatment, and the strategies to overcome bioavailability issues and new targets of curcumin in the ever-growing field of cancer.

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Curcumin Chemosensitizes 5-Fluorouracil Resistant MMR-Deficient Human Colon Cancer Cells in High Density Cultures

Cited by 115 publications

References 54 publications

Evidence That Calebin A, a Component of Curcuma Longa Suppresses NF-κB Mediated Proliferation, Invasion and Metastasis of Human Colorectal Cancer Induced by TNF-β (Lymphotoxin)

Evidence That Calebin A, a Component of Curcuma Longa Suppresses NF-κB Mediated Proliferation, Invasion and Metastasis of Human Colorectal Cancer Induced by TNF-β (Lymphotoxin)

Highly Bioavailable Forms of Curcumin and Promising Avenues for Curcumin-Based Research and Application: A Review

New insights into therapeutic activity and anticancer properties of curcumin

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