Heparin regulates colon cancer cell growth through p38 mitogen‐activated protein kinase signalling

Chatzinikolaou, Georgia; Nikitovic, Dragana; Berdiaki, Aikaterini; Zafiropoulos, Alexandros; Katonis, Pavlos; Karamanos, Nikos K.; Tzanakakis, George N.

doi:10.1111/j.1365-2184.2009.00649.x

Cited by 18 publications

(13 citation statements)

References 53 publications

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“…These results demonstrate that the induction of cytotoxicity and apoptosis by ACAN are mediated by p38 MAPK signalling. In previous studies, the polyphenols of olive oil were found to inhibit p38 phosphorylation, thereby initiating anti-proliferative effects in human colon adenocarcinoma cells (Chatzinikolaou et al, 2010;Corona et al, 2007). Additionally, anandamide, desferrioxamine, and brucein D have been shown to induce apoptosis through activation of the p38 pathway, which appears to be modulated in human cancer cells (Hsu et al, 2007).…”

Section: Discussionmentioning

confidence: 95%

Acanthoic acid induces cell apoptosis through activation of the p38 MAPK pathway in HL-60 human promyelocytic leukaemia

et al. 2012

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Section: Discussionmentioning

confidence: 95%

Acanthoic acid induces cell apoptosis through activation of the p38 MAPK pathway in HL-60 human promyelocytic leukaemia

et al. 2012

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“…Recently, it was shown that the overexpression of p53 decreases FAK mRNA and protein levels in colon carcinoma cells (18) On the other hand, nuclear transcription factor-kB (NF-kB) was demonstrated to stimulate FAK promoter activation and consequent upregulation of its expression (17). Heparin and its derivatives have previously been suggested to modulate p53 expression (29)(30)(31) or to inhibit NF-kB translocation to nucleus and consequently its transcriptional activity (32).…”

Section: Discussionmentioning

confidence: 99%

Heparin plays a key regulatory role via a p53/FAK‐dependent signaling in melanoma cell adhesion and migration

Chalkiadaki¹,

Nikitovic²,

Berdiaki³

et al. 2011

IUBMB Life

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SummaryHeparin and its various derivatives affect cancer progression in humans. In this study, we show that heparin uptaken intracellularly by melanoma cells activated a signaling cascade, which in turn inhibited melanoma cell adhesion and migration. The reduced ability of M5 cells to adhere onto the fibronectin (FN) substrate was directly correlated to a decrease in the expression of focal adhesion kinase (FAK), which is a key regulator of melanoma motility. Cell treatment with heparin caused a marked downregulation in FAK expression (P 0.01). This is followed by an analogous inhibition of both constitutive and FN-induced FAK Y397-phosphorylation (P 0.01). Moreover, heparin stimulated the p53 expression (P 0.001) of M5 cells and its increased accumulation in the nucleus. This favors a decrease in FAK promoter activation and explains the reduced FAK transcript and protein levels. In conclusion, the results of this study clearly demonstrate that the action of heparin in the regulation of melanoma cell adhesion and migration involves a p53/FAK/signaling pathway, which may be of importance in molecular targeted therapy of the disease.

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“…ERK responds to mitogenic stimuli and plays a particularly critical role in cell growth, survival and differentiation (Lai et al, 2010;Mao et al, 2008); while JNK/p38MAPK are activated mostly in response to a variety of stress signals and pathological damages as well as mitogenic stimuli. Their effects can be manifest by promoting or inhibiting apoptosis, which mainly depends on the signal patterns and/or cell subtypes (Chatzinikolaou et al, 2010;Zhang et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

Diterpenoid C of Radix Curcumae: An inhibitor of proliferation and inducer of apoptosis in human colon adenocarcinoma cells acting via inhibiting MAPK signaling pathway

Shen

Lü

Zhang

et al. 2014

Pharmaceutical Biology

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Context: Radix Curcumae is a traditional Chinese medicine that possesses antitumor properties, from which a new compound, diterpenoid C, was previously isolated and characterized. Objective: In this study, using human colon adenocarcinoma SW620 cells, we further investigated the antitumor effects of diterpenoid C and the underlying mechanisms. Materials and methods: Cell proliferation was assessed with the MTT assay. Cell apoptosis and cell-cycle progression were analyzed with flow cytometry. The expression of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (p38 MAPK), and their phosphorylated forms, as well as caspase-3 protein levels were examined with Western blots. Results: Diterpenoid C could inhibit the proliferation of SW620 cells in a dose-and timedependent manner. The median inhibitory concentration (IC 50 ) at 24, 48, and 72 h were 28.31, 15.58, and 6.14 mg/ml, respectively. The inhibition of proliferation was found to be statistically significant as compared with the well-established drugs 5-fluorouracil (5-Fu) and oxaliplatin (L-OHP) (p50.01). Diterpenoid C also induced apoptosis and arrested cell cycle. It showed the highest apoptosis rate (98.20 ± 0.91%) at 70 mg/ml, at 72 h. Meanwhile, diterpenoid C suppressed the phosphorylation of ERK, JNK, and p38 MAPK proteins, and markedly induced the cleavage of caspase 3. Discussion and conclusion: Diterpenoid C inhibits proliferation and induces apoptosis of cancer cells by suppressing the MAPK signaling pathway and inducing apoptotic factor caspase-3. Our results suggest that this novel compound might become a potent chemotherapeutic agent for the treatment of colon cancer and further studies are warranted.

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Heparin regulates colon cancer cell growth through p38 mitogen‐activated protein kinase signalling

Abstract: This study demonstrates that an extracellular glycosaminoglycan, heparin, finely modulates expression of genes crucial to cell cycle regulation through specific activation of p38 MAP kinase to stimulate colon cancer cell growth.

Cited by 18 publications

References 53 publications

Acanthoic acid induces cell apoptosis through activation of the p38 MAPK pathway in HL-60 human promyelocytic leukaemia

Acanthoic acid induces cell apoptosis through activation of the p38 MAPK pathway in HL-60 human promyelocytic leukaemia

Heparin plays a key regulatory role via a p53/FAK‐dependent signaling in melanoma cell adhesion and migration

Diterpenoid C of Radix Curcumae: An inhibitor of proliferation and inducer of apoptosis in human colon adenocarcinoma cells acting via inhibiting MAPK signaling pathway

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