Amygdalin as a Promising Anticancer Agent: Molecular Mechanisms and Future Perspectives for the Development of New Nanoformulations for Its Delivery.

Cancer rates are increasing, and cancer is one of the main causes of death worldwide. Amygdalin, also known as vitamin B17 (and laetrile, a synthetic compound), is a cyanogenic glycoside compound that is mainly found in the kernels and pulps of fruits. This compound has been proposed for decades as a promising naturally occurring substance which may provide anticancer effects. This is a comprehensive review which critically summarizes and scrutinizes the available studies exploring the anticancer effect of amygdalin, highlighting its potential anticancer molecular mechanisms as well as the need for a nontoxic formulation of this substance. In-depth research was performed using the most accurate scientific databases, e.g., PubMed, Cochrane, Embase, Medline, Scopus, and Web of Science, applying effective, characteristic, and relevant keywords. There are several pieces of evidence to support the idea that amygdalin can exert anticancer effects against lung, breast, prostate, colorectal, cervical, and gastrointestinal cancers. Amygdalin has been reported to induce apoptosis of cancer cells, inhibiting cancer cells' proliferation and slowing down tumor metastatic spread. However, only a few studies have been performed in in vivo animal models, while clinical studies remain even more scarce. The current evidence cannot support a recommendation of the use of nutritional supplements with amygdalin due to its cyano-moiety which exerts adverse side effects. Preliminary data have shown that the use of nanoparticles may be a promising alternative to enhance the anticancer effects of amygdalin while simultaneously reducing its adverse side effects. Amygdalin seems to be a promising naturally occurring agent against cancer disease development and progression. However, there is a strong demand for in vivo animal studies as well as human clinical studies to explore the potential prevention and/or treatment efficiency of amygdalin against cancer. Moreover, amygdalin could be used as a lead compound by effectively applying recent developments in drug discovery processes.

Complementary CRISPR genome-wide genetic screens in PARP10-knockout and overexpressing cells identify synthetic interactions for PARP10-mediated cellular survival.

PARP10 is a mono-ADP-ribosyltransferase with multiple cellular functions, including proliferation, apoptosis, metabolism and DNA repair. PARP10 is overexpressed in a significant proportion of tumors, particularly breast and ovarian cancers. Identifying genetic susceptibilities based on PARP10 expression levels is thus potentially relevant for finding new targets for precision oncology. Here, we performed a series of CRISPR genome-wide loss-of-function screens in isogenic control and PARP10-overexpressing or PARP10-knockout cell lines, to identify genetic determinants of PARP10-mediated cellular survival. We found that PARP10-overexpressing cells rely on multiple DNA repair genes for survival, including ATM, the master regulator of the DNA damage checkpoint. Moreover, we show that PARP10 impacts the recruitment of ATM to nascent DNA upon replication stress. Finally, we identify the CDK2-Cyclin E1 complex as essential for proliferation of PARP10-knockout cells. Our work identifies a network of functionally relevant PARP10 synthetic interactions, and reveals a set of factors which can potentially be targeted in personalized cancer therapy.

Beneficial role of Boehmeria nivea in health and phytochemical constituents.

The leaf and stem extracts of Boehmeria nivea (BN) collected from three different regions in Korea were screened for their antioxidant, neuroprotective, estrogenic, insulin secretion, and α-glucosidase inhibitory activity. We also examined whether BN extracts regulate cancer cell growth, inflammatory-related gene expression, and lipid accumulation in cellular system. Leaf extracts possessed greater antioxidant, anti-proliferative in cancer cells, neuroprotective, estrogenic activity, and inhibitory effect on pro-inflammatory gene expression than stem extracts. Leaf and stem extracts inhibited lipid accumulation in three T3-L1 adipocytes but did not affect glucose-stimulated insulin secretion in INS-1 cells. We isolated and identified the phytochemical constituents in the n-butanol and ethyl acetate fractions of BN leaves by combining silica gel column chromatography with mass spectrometry and 1 H- and 13 C-NMR analysis. The active compounds (caffeic acid, isoquercitrin, p-coumaric acid, and rutin) exhibited ABTS and DPPH radical scavenging activity, which may contribute to the biological activities of BN leaf extract. An analytical method was developed to quantify marker compounds for the discrimination of BN collected from different regions. Our results support the use of this analysis method for accurate identification and quantification of marker compounds in BN for the development of functional foods. PRACTICAL APPLICATIONS: Boehmeria nivea (BN) has been used as a raw material for the textile industry or traditional herbal medicine. The current study established the biological activities and active components of BN. Our results showed that BN leaf and stem extracts exhibit antioxidant, neuroprotective, and estrogenic activity. BN leaf extract also inhibited cancer cell growth, inflammatory mediators and cytokines production, and lipid accumulation in vitro. Moreover, the bioactive compounds, such as caffeic acid, isoquercitrin, p-coumaric acid, and rutin, exert ABTS and DPPH radical scavenging activities. Therefore, BN could potentially be a promising source of bioactive phytochemicals for the development of functional foods or drugs.

Lignans and Neolignans with Antioxidant and Human Cancer Cell Proliferation Inhibitory Activities from Cinnamomum bejolghota Confirm Its Functional Food Property.

In the aim to evaluate the functional food property of Cinnamomum bejolghota, seven new lignans and neolignans, bejolghotins A-G (1-4 and 9-11), along with 14 known ones (5-8 and 12-21), were isolated and their structures including absolute configurations were elucidated by extensive spectroscopic data and electronic circular dichroism (ECD) analyses. All of the isolates were tested for antioxidant and human cancer cell proliferation inhibitory activities. Twenty compounds showed comparable antioxidant activity to the positive controls, and three significantly inhibited the growth of three cancer cell lines HCT-116, A549, and MDA-MB-231 with IC50 values of 0.78-2.93 µM, which confirmed its health benefits.

The double effect of walnut septum extract (Juglans regia L.) counteracts A172 glioblastoma cell survival and bacterial growth.

Walnut (Juglans regia L.) is considered to be a 'superfood' for its multiple protective actions on human health. Walnut extracts have proven antitumor activity in different cancer cell lines. However, the efficacy of septum extract against glioblastoma has still not been investigated. Glioblastoma is the most difficult type of brain cancer to treat. The standard therapy, based on temozolomide, causes several side effects, including neutropenia and lymphocytopenia, which often favor the onset of opportunistic infections. In the present study, the chemical profile of the Sicilian walnut septum ethanolic extract was analyzed using high­performance liquid chromatography (HPLC)­diode array detection and HPLC­electrospray ionization tandem mass spectrometry. The potential cytostatic activity of the extract against the human A172 glioblastoma cell line was investigated and the results showed that the extract could decrease cancer cell proliferation and migration. Using cytofluorimetric analyses and caspase­3 assays, the pro­apoptotic action of walnut extract was demonstrated. Furthermore, the evaluation of the antibacterial activity highlighted the efficacy of the extract in reducing Gram­positive and Gram­negative bacterial growth, most of which were resistant to the antibiotic, ciprofloxacin. Finally, Prediction of Activity Spectra for Substances analysis showed the predicted antitumor and antibacterial activity of HPLC detected compounds. The promising results could provide novel perspective in the field of chemotherapeutic co­adjuvants.

The light subunit of mushroom Agaricus bisporus tyrosinase: Its biological characteristics and implications.

The light subunit of mushroom Agaricus bisporus tyrosinase (LSMT) is a protein of unknown function that was discovered serendipitously during the elucidation of the crystal structure of the enzyme. The protein is non-immunogenic and can penetrate the intestinal epithelial cell barrier, and thus, similar to its structural homologue HA-33 from Clostridium botulinum, may be potentially absorbable by the intestine. LSMT also shares high structural homology with the ricin-B-like lectin from the mushroom Clitocybe nebularis (CNL), which has been shown to display biological activity against leukemic cancer cells and dendritic cells. Therefore, we evaluated the biological activity of LSMT. An in vitro assay suggested that LSMT presentation to most of the cancer cell lines studied has a negligible effect on their proliferation. However, inhibition of cell growth and a slight stimulation of cell proliferation were observed with breast cancer and macrophage cells, respectively. LSMT appeared to be relatively resistant against proteolysis by trypsin and papain, but not bromelain. Challenges with gastric and intestinal juice suggested that the protein is resistant to gastrointestinal tract conditions. This is the first report on the biological characteristics and implication of LSMT.

Effect of constituents from samaras of Austroplenckia populnea (Celastraceae) on human cancer cells.

BACKGROUND: Aiming the continuity of the studies of Austroplenckia populnea, Brazilian species of the Celastraceae family, in the present study, it was investigated the effect of crude extracts obtained with ethanol, ethyl acetate and chloroform and two purified constituents, proanthocyanidin A and 4'-O-methylepigallocatechin, both isolated from its samaras, on cancer cell proliferation assays. MATERIALS AND METHODS: The human cancer cells lines MCF-7 (ductal breast carcinoma), A549 (lung cancer), HS578T (ductal breast carcinoma) and non-cancer HEK293 (embryonic kidney cells) were treated with different concentrations of extracts and constituents and the effect was observed through the acid phosphatase method. The chemical structures of the purified compounds were identified by the respective IR and (1)H and (13)C nuclear magnetic resonance spectral data. RESULTS: While crude extracts from samaras of the folk medicine A. populnea can trigger cell proliferative effects in human cell lines, the purified compounds (proanthocyanidin A and 4'-O-methyl-epigallocatechin) isolated from the same extracts can have an opposite (anti-proliferative) effect. CONCLUSION: Based on the results, it was possible to suggest that extracts from samaras of A. populnea should be further investigated for possible cancer-promoting activities; and the active extracts can also represent a source of compounds that have anti-cancer properties.

Structural characterization of a broccoli polysaccharide and evaluation of anti-cancer cell proliferation effects.

Broccoli is a widely consumed vegetable with abundant amount of nutrients, which bring numerous beneficial effects on human health. The structural information of water-soluble polysaccharides in broccoli was eludicated for the first time in this work. A purified polysaccharide fraction (BPCa) was obtained by column chromatography. It comprised of arabinose (Ara), galactose (Gal), rhamnose (Rha) with a molar ratio of 5.3:0.8:1.0. Nuclear magnetic resonnance spectra data revealed that α-L-1,5-Araf and α-L-1,3,5-Araf are present in the backbone, while α-L-Araf terminal was attended in side chain. α-L-1,2-Rhap was found to be linked to α-L-1,5-Araf in heteronuclear multiple bond correlation spectra. The presences of ß-D-1,4-Galp and α-D-1,4-GalpA were also detected. Furthermore, BPCa showed significant anti-cancer cell proliferation activities against HepG2, Siha and MDA-MB-231 carcinoma cell lines. The results indicated that BPCa had a good potential to be applied as functional food additives.

Identification of phenolics in litchi and evaluation of anticancer cell proliferation activity and intracellular antioxidant activity.

Litchi leaf is a good resource for phenolics, which are good candidates for medicines. In this work, three phenolics were isolated from litchi leaf by column chromatography. Their structures were identified by electrospray ionization-mass spectrometry (ESI-MS) and nuclear magnetic resonance (NMR) spectroscopy as secoisolariciresinol 9'-O-ß-D-xyloside (1), 4,7,7',8',9,9'-hexahydroxy-3,3'-dimethoxy-8,4'-oxyneolignan (2), and cinnamtannin B1 (3). Cinnamtannin B1 showed better extra- and intracellular antioxidant activities than Compounds 1 and 2. The intracellular antioxidant activity of cinnamtannin B1 was related to the upregulation of endogenous antioxidant enzyme activities (superoxide dismutase, catalase, and glutathione peroxidase), and inhibition of ROS generation. Furthermore, cinnamtannin B1 exhibited strong antiproliferative effects against HepG2 and Siha cell lines with no significant cytotoxicities. In the case of the HepG2 cell line, cell cycle arrest and apoptosis induction were the underlying anticancer mechanisms of cinnamtannin B1. The results indicated that cinnamtannin B1 was a potent cancer cell proliferation inhibitor and a good intracellular antioxidant.

EFFECTS OF SELENIUM, VITAMIN A AND E ON HUMAN BREAST CANCER CELL PROLIFERATION / 营养学报

The study was conducted in vitro with human breast cancer cells BCaP-37, to determine the effects of selenium, vitamin A, vitamin E and a combination of these three nutrients on cell proliferation and cellular nucleic acid content. Selenium as sodium selenite had two phases of effect on cancer cell proliferation: the low concentrations of selenium (less than 5 ?M) stimulated cell growth and increased the cellular nucleic acid content; the high concentrations (more than 5 ?M) depressed cell growth and reduced the cellular nucleic acid content with dose-dependence. Vitamin A acetate inhibited cancer cell growth significantly, but vitamin A acid inhibited to some extent, and was less effective than vitamin A acetate. Vitamin E had less inhibitory effect compared to vitamin A acetate and the inhibitory percentages were lower than 40% in all treatment groups. Combination of selenium (5 ?M) and vitamin E (20mg/L) or selenium and vitamin A acetate (2mg/L), no synergism for the reduction of the contents of cellular nucleic acids (DNA and RNA) were observed. The combination of selenium, vitamin A acetate and vitamin E at such levels reduced cellular DNA and RNA contents obviously; RNA content was significantly lower than any other treatment group and was reduced synergis-tically. It was indicated that the combination of selenium, vitamin A acetate, vitamin E was synergistic for inhibition of cell proliferation. Results also showed the reversible tendency in the inhibition of cell proliferation by combination of these three nutrients. It was suggested that combination of selenium, vitamin A and E might be benificial for the prevention and adjuvant treatment of human breast cancer.