crocin and Carcinoma

Angiogenesis and metastasis play pivotal roles in the progression of cancer. We recently discovered that crocin, a dietary carotenoid derived from the Himalayan crocus, inhibited the growth of colon cancer cells. However, the exact role of crocin on the angiogenesis and metastasis in colorectal cancer remains unclear. In the present study, we demonstrated that crocin significantly reduces the viability of colon cancer cells (HT-29, Caco-2) and human umbilical vein endothelial cells (HUVEC), but was not toxic to human colon epithelial (HCEC) cells. Furthermore, pre-treatment of human carcinoma cells (HT-29 and Caco-2) with crocin inhibited cell migration, invasion, and angiogenesis in concentration -dependent manner. Further studies demonstrated that crocin inhibited TNF-α, NF-κB and VEGF pathways in colon carcinoma cell angiogenesis and metastasis. Crocin also inhibited cell migration, invasion, and tube formation in human umbilical vein endothelial cells (HUVEC) in a concentration -dependent manner. We also observed that crocin significantly reduced the secretion of VEGF and TNF-α induced activation of NF-kB by human colon carcinoma cells. In the absence of TNF-α, a concentration-dependent reduction in NF-kB was observed. Many of these observations were confirmed by in vivo angiogenesis models, which showed that crocin significantly reduced the progression of tumour growth. Collectively, these finding suggest that crocin inhibits angiogenesis and colorectal cancer cell metastasis by targeting NF-kB and blocking TNF-α/NF-κB/VEGF pathways.

Topics: Caco-2 Cells; Carcinoma; Carotenoids; Colonic Neoplasms; Human Umbilical Vein Endothelial Cells; Humans; Neovascularization, Pathologic; NF-kappa B; Tumor Necrosis Factor-alpha; Vascular Endothelial Growth Factor A

Crocin is a pharmacologically active component of Crocus sativus. It is an unusual water-soluble carotenoid responsible for the red color of saffron. In various studies, the anticancer effect of saffron and its constituents has been established. Polyethylene glycolated nanoliposomes with a size range up to 200 nm are suitable for encapsulation of cytotoxic drugs and can target tumors passively through the enhanced permeation and retention effect. The aim of this study was to develop a nanoliposomal formulation containing crocin with a higher therapeutic index for the treatment of cancer. Four formulations of polyethylene glycolated nanoliposomes containing 25 mg/ml crocin were prepared with hydrogenated soy phosphatidylcholine, cholesterol, and methoxy-polyethylene glycol (MW 2000)-distearoylphosphatidylcholine at different molar ratios by a solvent evaporation method plus extrusion. Then the liposomes were characterized for their size, zeta potential, crocin encapsulation, release properties, and in vitro cytotoxicity against C26 colon carcinoma cells. Based on in vitro results, the best formulation was selected for an in vivo study, and its antitumor activity was evaluated in BALB/c mice bearing C26 colon carcinoma. The IC50 of crocin itself against C26 colon carcinoma was 0.73 mM. The characterization of the best formulation was as follow: Z-average size: 127.6 ± 1.5 nm; polydispersity index: 0.087 ± 0.018; zeta potential: - 21.7 mV ± 6.7; % encapsulation: 84.62 ± 0.59; % release after 168 hours in RPMI 1640 containing 30 % FBS: 16.26 ± 0.01 %. Liposomal crocin at doses of 50 and 100 mg/kg significantly decreased tumor size and increased survival rate compared with PBS and crocin in buffer (100 mg/kg) groups. The results of this study indicated that liposomal encapsulation of crocin could increase its antitumorigenic activity. Thus, to obtain an optimal dose for use in humans, the formulation merits further investigation.

Topics: Animals; Antineoplastic Agents; Carcinoma; Carotenoids; Colon; Colonic Neoplasms; Crocus; Female; Liposomes; Mice; Mice, Inbred BALB C; Polyethylene Glycols; Tumor Cells, Cultured