Targeting different angiogenic pathways with combination of curcumin, leflunomide and perindopril inhibits diethylnitrosamine-induced hepatocellular carcinoma in mice

Nasr, Mustafa Abu; Selima, Eman; Hamed, Omar; Kazem, Amany

doi:10.1016/j.ejphar.2013.11.022

Cited by 34 publications

(23 citation statements)

References 37 publications

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“…To the best of our knowledge, furosemide has no therapeutic properties in cancer, although the combined use of angiotensin-converting enzyme inhibitors and curcumin has been associated with inhibition of angiogenesis and diminished tumour growth in HCC in mice (9).…”

Section: Discussionmentioning

confidence: 99%

Spontaneous regression of hepatocellular carcinoma in a Caucasian male patient: A case report and review of the literature

Noij

Linden

2016

Molecular and Clinical Oncology

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Abstract. Hepatocellular carcinoma (HCC) is the most common primary hepatic cancer. As it often presents at an advanced stage, it generally has a poor prognosis. Spontaneous regression is a rare finding in HCC, and is often associated with tumour ischemia or a systemic inflammatory response. We herein present the case of a Caucasian patient with spontaneous regression of advanced HCC, not associated with either mechanism. Our patient was a 74-year old Caucasian male who presented with advanced biopsy-proven HCC, with α-fetoprotein levels of >16,600 kU/l. On computed tomography examination, multiple metastases were identified. Due to the poor performance status and as the patient declined treatment, he was referred to a general practitioner for supportive palliative care. Six months later, the patient was alive and feeling well. He had suffered a cerebrovascular accident with ensuing partial hemiparesis, and had been initiated on enalapril, furosemide and curcumin. On re-evaluation, the lung lesions had disappeared, whereas both the liver and peritoneal lesions had decreased in size. Following a review of the literature, the conclusion was that this case of spontaneous regression of advanced HCC was not caused by ischemia, inflammation, or any other previously reported mechanism. Further research is required to elucidate the mechanisms underlying spontaneous regression of HCC.

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Section: Discussionmentioning

confidence: 99%

Spontaneous regression of hepatocellular carcinoma in a Caucasian male patient: A case report and review of the literature

Noij

Linden

2016

Molecular and Clinical Oncology

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“…HCC represents one of the most highly vascularized (“angiogenic”) solid tumors [41], and DEN-treated mice display increased liver angiogenesis; as such, strategic targeting of pro-angiogenic factors has become a major focus of solid cancer therapeutics [39,43,44]. From our observations we have determined that there is a marked increase in hepatic VE-cad + CD45 - SEC in mice subjected to either HFD or DEN, and histological evidence suggests an expanded but leaky vasculature in the liver.…”

Section: Discussionmentioning

confidence: 99%

Deciphering hepatocellular responses to metabolic and oncogenic stress

et al. 2015

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Each cell type responds uniquely to stress and fractionally contributes to global and tissue-specific stress responses. Hepatocytes, liver macrophages (MΦ), and sinusoidal endothelial cells (SEC) play functionally important and interdependent roles in adaptive processes such as obesity and tumor growth. Although these cell types demonstrate significant phenotypic and functional heterogeneity, their distinctions enabling disease-specific responses remain understudied. We developed a strategy for the simultaneous isolation and quantification of these liver cell types based on antigenic cell surface marker expression. To demonstrate the utility and applicability of this technique, we quantified liver cell-specific responses to high-fat diet (HFD) or diethylnitrosamine (DEN), a liver-specific carcinogen, and found that while there was only a marginal increase in hepatocyte number, MΦ and SEC populations were quantitatively increased. Global gene expression profiling of hepatocytes, MΦ and SEC identified characteristic gene signatures that define each cell type in their distinct physiological or pathological states. Integration of hepatic gene signatures with available human obesity and liver cancer microarray data provides further insight into the cell-specific responses to metabolic or oncogenic stress. Our data reveal unique gene expression patterns that serve as molecular “fingerprints” for the cell-centric responses to pathologic stimuli in the distinct microenvironment of the liver. The technical advance highlighted in this study provides an essential resource for assessing hepatic cell-specific contributions to metabolic and oncogenic stress, information that could unveil previously unappreciated molecular mechanisms for the cellular crosstalk that underlies the continuum from metabolic disruption to obesity and ultimately hepatic cancer.

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“…[75][76][77][78][79] Synergistic effects of curcumin have also been demonstrated in combined treatment with anti-angiogenic agents such as leflunomide and perindopril in in vivo mice models. [80] Thus, to conclude, curcumin has a lot of potential to act as an adjuvant remedy in liver cancer. As far as toxicity issue is concerned, herbal medicines are much safer, have less adverse effects and relatively cheaper than conventional medicines.…”

Section: Potential Side Effects Of Curcuminmentioning

confidence: 99%

Curcumin: an adjuvant therapeutic remedy for liver cancer

Sharma¹,

Tanwar²,

Gupta³

2016

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The molecular signalling pathways for hepatocellular carcinoma and hepatoblastoma have been extensively studied. The treatment of these highly vascular tumors mainly revolves around chemotherapy and surgery. Yet there is a high associated morbidity and mortality due to advanced stages, adverse effects owing to chemotherapy and recurrence. The role of Curcumin as an adjuvant remedy is explored in this article. Curcumin stimulates apoptosis of cancer cells, acts as anti-proliferative agent, has anti-angiogenic action, prevents tumor invasiveness and metastasis and prevents recurrence. It also has been proven to decrease the adverse effects of chemotherapeutic agents and has a synergistic anticancer action. It acts at the molecular level and affects the various metabolic pathways involved in tumorigenesis. It also promotes healing and has antiinflammatory, anti-oxidant and anti-infective action. This natural phytocompounds has immense anti-cancer potential and holds future promise as an adjuvant remedy to treat liver cancer.

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Targeting different angiogenic pathways with combination of curcumin, leflunomide and perindopril inhibits diethylnitrosamine-induced hepatocellular carcinoma in mice

Cited by 34 publications

References 37 publications

Spontaneous regression of hepatocellular carcinoma in a Caucasian male patient: A case report and review of the literature

Spontaneous regression of hepatocellular carcinoma in a Caucasian male patient: A case report and review of the literature

Deciphering hepatocellular responses to metabolic and oncogenic stress

Curcumin: an adjuvant therapeutic remedy for liver cancer

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