Effects of curcumin in pediatric epithelial liver tumors: inhibition of tumor growth and alpha-fetoproteinin vitroandin vivoinvolving the NFkappaB- and the beta-catenin pathways

Abstract

In children with hepatocellular carcinoma (pHCC) the 5-year overall survival rate is poor. Effects of cytostatic therapies such as cisplatin and doxorubicin are limited due to chemoresistance and tumor relapse. In adult HCC, several antitumor properties are described for the use of curcumin. Curcumin is one of the best-investigated phytochemicals in complementary oncology without relevant side effects. Its use is limited by low bioavailability. Little is known about the influence of curcumin on pediatric epithelial hepatic malignancies. We investigated the effects of curcumin in combination with cisplatin on two pediatric epithelial liver tumor cell lines. As mechanisms of action inhibition of NFkappaB, beta-catenin, and decrease of cyclin D were identified. Using a mouse xenograft model we could show a significant decrease of alpha-fetoprotein after combination therapy of oral micellar curcumin and cisplatin. Significant concentrations of curcuminoids were found in blood samples, organ lysates, and tumor tissue after oral micellar curcumin administration. Micellar curcumin in combination with cisplatin can be a promising strategy for treatment of pediatric HCC.

Improving anti-melanoma effect of curcumin by biodegradable nanoparticles

“…A large number of studies have shown that curcumin has a broad-spectrum anti-tumor effect [ 18 – 27 ]. Curcumin can not only directly inhibit tumor cell proliferation but also induce cell apoptosis by regulating cell cycle, activating endogenous and exogenous pathways.…”

“…Curcumin is a natural component extracted from traditional Asian spice turmeric with various potential activities such as anti-oxidant, anti-septic, anti-inflammatory, anti-biotic, anti-amyloid and anti-thrombosis [ 15 – 17 ]. Recently, researches have proposed its promising anticancer role in colon cancer, breast cancer, liver cancer, head and neck cancer, ovarian cancer, prostate cancer, non-small cell lung cancer, and pancreatic cancer [ 18 – 27 ]. Despite of being inexpensive and nontoxic, the unfavorable bioavailability which caused by poor absorption, quick metabolism and system elimination restricts the application of curcumin as an anti-cancer agent [ 17 , 28 , 29 ].…”

Dietary phytochemicals and cancer chemoprevention: a review of the clinical evidence

“…In recent decades, in vitro models have shown that curcumin inhibits the growth of a variety of cell lines by inducing cell cycle arrest and apoptosis, most importantly through pleiotropic modulation on several distinct cancer targets including nuclear factor kappa B (NF-κB), cyclooxygenase-2 (COX-2), tumor necrosis factor alpha (TNF-α), STAT-3 and cyclin D1 [23–26]. Building upon pre-clinical work, several phase I clinical trials have confirmed both the safety and pharmacokinetics of curcumin in patients with doses escalated up to eight grams per day, and these trials have shown measurable biological effects in patients with a variety of malignancies including pancreatic cancer, multiple myeloma and advanced colorectal cancer refractory to standard chemotherapy [27–30].…”

Is hepatocellular carcinoma the same disease in children and adults? Comparison of histology, molecular background, and treatment in pediatric and adult patients

“…Stable disease in a pediatric HCC patient was seen in a phase I trial of the VEGF‐trapping agent aflibercept . Worth mentioning is the preliminary promise of curcumin in pediatric HCC cell lines and orthotopic models . This phytochemical with few side effects in adult patients has shown antitumor effects in adult HCC.…”

“…40 Worth mentioning is the preliminary promise of curcumin in pediatric HCC cell lines and orthotopic models. 54 This phytochemical with few side effects in adult patients has shown antitumor effects in adult HCC. NFKB1, CTNNB1, and CCND1 are its molecular targets.…”