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In the present study, we developed a novel drug-like self-micellizing anticancer lipid (SMAL), and investigated its anticancer activity and effects on cell death pathways in human colorectal cancer (CRC) cell lines. Three self-assembled nanoparticles were prepared, namely, SMAL102 (lauramide derivative), SMAL104 (palmitamide derivative), and SMAL108 (stearamide derivative) by a thin-film hydration technique, and were characterized for physicochemical and biological parameters. SMAL102 were nanosized (160.23 ± 8.11 nm) with uniform spherical shape, while SMAL104 and SMAL108 did not form spherical shape but formed large size nanoparticles and irregular in shape. Importantly, SMAL102 showed a cytotoxic effect towards CRC cell lines (HCT116 and HT-29), and less toxicity to a normal colon fibroblast cell line (CCD-18Co). Conversely, SMAL104 and SMAL108 did not have an anti-proliferative effect on CRC cell lines. SMAL102 nanoparticles were actively taken up by CRC cell lines, localized in the cell membrane, and exhibited remarkable cytotoxicity in a concentration-dependent manner. The normal colon cell line showed significantly less cellular uptake and non-cytotoxicity as compared with the CRC cell lines. SMAL102 nanoparticles induced caspase-3, caspase-9, and PARP cleavage in HT-29 cells, indicating the induction of apoptosis; whereas LC3B was activated in HCT116 cells, indicating autophagy-induced cell death. Collectively, these results demonstrate that SMAL102 induced cell death via activation of apoptosis and autophagy in CRC cell lines. The present study could be a pioneer for further preclinical and clinical development of such compounds. [ABSTRACT FROM AUTHOR]

Aim of the study In this study, we examined the effect of different fractions and components of Chaga mushroom (Inonotus Obliquus) on viability and apoptosis of colon cancer cells. Among them, one component showed the most effective growth inhibition and was identified as ergosterol peroxide by NMR analysis. We investigated the anti-proliferative and apoptosis mechanisms of ergosterol peroxide associated with its anti-cancer activities in human colorectal cancer (CRC) cell lines and tested its anti-tumor effect on colitis-induced CRC developed by Azoxymethane (AOM)/Dextran sulfate sodium (DSS) in a mouse model. Materials and methods We used MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assays, flow cytometry assays, Western blot analysis, colony formation assays, reverse transcription-polymerase chain reaction (RT-PCR), immunohistochemistry (IHC), and AOM/DSS mouse models to study the molecular mechanism of metastatic activities in CRC cells. Results Ergosterol peroxide inhibited cell proliferation and also suppressed clonogenic colony formation in HCT116, HT-29, SW620 and DLD-1 CRC cell lines. The growth inhibition observed in these CRC cell lines was the result of apoptosis, which was confirmed by FACS analysis and Western blotting. Ergosterol peroxide inhibited the nuclear levels of β-catenin, which ultimately resulted in reduced transcription of c-Myc, cyclin D1, and CDK-8. Ergosterol peroxide administration showed a tendency to suppress tumor growth in the colon of AOM/DSS-treated mice, and quantification of the IHC staining showed a dramatic decrease in the Ki67-positive staining and an increase in the TUNEL staining of colonic epithelial cells in AOM/DSS-treated mice by ergosterol peroxide for both prevention and therapy. Conclusion Our data suggest that ergosterol peroxide suppresses the proliferation of CRC cell lines and effectively inhibits colitis-associated colon cancer in AOM/DSS-treated mice. Ergosterol peroxide down-regulated β-catenin signaling, which exerted anti-proliferative and pro-apoptotic activities in CRC cells. These properties of ergosterol peroxide advocate its use as a supplement in colon cancer chemoprevention. [ABSTRACT FROM AUTHOR]

• [6]-Gingerol [(S)-5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-3-decanone] is a phenolic substance with several pharmacological properties. • [6]-Gingerol showed antitumoral effects in primary cells of Sarcoma 180 as well as in peripheral blood lymphocytes of mice. • [6]-Gingerol induced cytogenetic changes in S-180 cells, biomarkers of genotoxicity, mutagenicity, apoptosis and necrosis. • [6]-Gingerol may be an antitumoral agent with mechanisms associated with reducing genetic instability inducing apoptosis. [6]-Gingerol [(S)-5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-3-decanone] is a phenolic substance reported for several ethnopharmacological usage by virtue of its antioxidant, antiemetic, anti-inflammatory and anticancer properties. This study assessed the antitumoral effects of [6]-Gingerol in primary cells of Sarcoma 180 as well as in peripheral blood lymphocytes of mice. The effect of [6]-Gingerol was assessed by applying cytogenetic biomarkers as indicative of genotoxicity, mutagenicity and apoptosis. Ascitic liquid cells were treated with [6]-Gingerol at concentrations of 21.33, 42.66 and 85.33 μM and subjected to the cytotoxicity assays using Trypan blue test and the comet assay, as well as the cytokinesis-block micronucleus assay. Doxorubicin (6 μM) and hydrogen peroxide (85.33 μM) were used as positive controls. [6]-Gingerol, especially at concentrations of 42.66 and 85.33 μM, showed notable cytotoxicity in Sarcoma 180 cells by reducing cell viability and cell division rates via induction of apoptosis. Genotoxicity at the concentrations used was punctuated by the increase in the index and frequency of DNA damage in tested groups. [6]-Gingerol, at all concentrations tested, did not induce significant aneugenic and/or clastogenic effects. It did, however, induced other nuclear abnormalities, such as nucleoplasmic bridges, nuclear buds and apoptosis. The genotoxic effects observed in the cotreatment with H 2 O 2 (challenge assay) employing neoplastic and healthy cells, indicated that [6]-Gingerol may induce oxidative stress. Observations suggest that [6]-Gingerol may be a candidate for pharmaceutical antitumoral formulations due to its cytotoxicity and to mechanisms associated with genetic instability generated by nuclear alterations especially by apoptosis. [ABSTRACT FROM AUTHOR]