Anticancer Effects of the Corchorus olitorius Aqueous Extract and Its Bioactive Compounds on Human Cancer Cell Lines.

Corchorus olitorius is a common, leafy vegetable locally known as "Saluyot" in the Philippines. Several studies have reported on its various pharmacological properties, such as antioxidant, anti-inflammatory, analgesic, and anticancer properties. However, little is known about its effects on angiogenesis. This study aimed to evaluate the anticancer properties, such as the antiproliferative, anti-angiogenic, and antitumor activities, of the C. olitorius aqueous extract (CO) and its bioactive compounds, chlorogenic acid (CGA) and isoquercetin (IQ), against human melanoma (A-375), gastric cancer (AGS), and pancreatic cancer (SUIT-2), using in vitro and in ovo biological assays. The detection and quantification of CGA and IQ in CO were achieved using LC-MS/MS analysis. The antiproliferative, anti-angiogenic, and antitumor activities of CO, CGA, and IQ against A-375, AGS, and SUIT-2 cancer cell lines were evaluated using MTT and CAM assays. CGA and IQ were confirmed to be present in CO. CO, CGA, and IQ significantly inhibited the proliferation of A-375, AGS, and SUIT-2 cancer cells in a dose-dependent manner after 48 h of treatment. Tumor angiogenesis (hemoglobin levels) of A-375 and AGS tumors was significantly inhibited by CO, CGA, IQ, and a CGA-IQ combination. The growth of implanted A-375 and AGS tumors was significantly reduced by CO, CGA, IQ, and a CGA-IQ combination, as measured in tumor weight. Our investigation provides new evidence to show that CO has promising anticancer effects on various types of human cancer cells. CO and its compounds are potential nutraceutical products that could be used for cancer treatment.

A New Eucalyptol-Rich Lavender (Lavandula stoechas L.) Essential Oil: Emerging Potential for Therapy against Inflammation and Cancer.

BACKGROUND/AIM: natural products are a potential source for drug discovery and development of cancer chemoprevention. Considering that drugs currently available for the treatment of inflammatory and cancer conditions show undesirable side effects, this research was designed to evaluate, for the first time, the in vitro anticancer activity of Algerian Lavandula stoechas essential oil (LSEO) against different cancer cell lines, as well as its in vitro and in vivo topical and acute anti-inflammatory properties. MATERIALS AND METHODS: the LSEO was extracted by steam distillation, and chemical composition analysis was performed using gas chromatography. The main compounds identified in LSEO were oxygenated monoterpenes, such as 1,8-Cineole (61.36%). LSEO exhibited a potent anti-inflammatory activity using the xylene-induced mouse ear edema model. RESULTS: LSEO (200 and 20 mg/kg) was able to significantly reduce (p < 0.05) the carrageenan-induced paw edema with a similar effect to that observed for the positive control. Topical application of LSEO at doses of 82 and 410 mg/kg significantly reduced acute ear edema in 51.4% and 80.1% of the mice, respectively. Histological analysis confirmed that LSEO inhibited the skin inflammatory response. Moreover, LSEO was tested for its antitumor activity against different cancer cell lines. LSEO was found to be significantly active against human gastric adenocarcinoma (AGS), Melanoma MV3, and breast carcinoma MDA-MB-231 cells, with median inhibitory concentration (IC50) values of 0.035 ± 0.018, 0.06 ± 0.022 and 0.259 ± 0.089 µL/mL, respectively. Altogether, these results open a new field of investigation into the characterization of the molecules involved in anti-proliferative processes. CONCLUSION: We suggest that LSEO, with 1,8-Cineole as the major active component, is a promising candidate for use in skin care products with anti-inflammatory and anticancer properties. The results of this study may provide an experimental basis for further systematic research, rational development, and clinical utilization of lavender resources.

Senescent Colon and Breast Cancer Cells Induced by Doxorubicin Exhibit Enhanced Sensitivity to Curcumin, Caffeine, and Thymoquinone.

Cellular senescence is a process of physiological growth arrest that can be induced by intrinsic or extrinsic stress signals. Some cancer therapies are associated with senescence of cancer cells with a typical cell cycle arrest. Doxorubicin (Dox) induces senescence by a p53-dependent pathway and telomere dysfunction of numerous cancers. However, cellular senescence induces suppression in proliferation activity, and these cells will remain metabolically active and play an important role in tumor relapse and development of drug resistance. In the current study, we investigated the apoptotic effect of curcumin (Cur), caffeine (Caff), and thymoquinone (TQ) on senescent colon cancer HCT116 and breast cancer MCF7 cell lines treated with Dox. Results showed typical senescence markers including decreased bromodeoxyuridine incorporation, increased accumulation of senescence-associated ß-galactosidase (SA-ß-gal), cell cycle arrest, and upregulation of p53, P-p53, and p21 proteins. Annexin-V analysis by flow cytometry revealed 2- to 6-fold increases in annexin-V-positive cells in Dox-treated MCF7 and HCT116 cells by Cur (15 µM), Caff (10 mM), and TQ (50 µM; P < .001). In comparison between proliferative and senescent of either HCT116 or MCF7 cells, Caff at 15 mM and TQ at 25 µM induced significant increases in apoptosis of Dox-treated cells compared with proliferative cells (P < .001). Data revealed that Cur, Caff, and TQ potentially induced apoptosis of both proliferative and senescent HCT116 and MCF7 cells. In vivo and clinical trials are of great importance to validate this result.

Novel Targeted Nano-Parthenolide Molecule against NF-kB in Acute Myeloid Leukemia.

The targeted nano-encapsulation of anticancer drugs can improve drug delivery and the selective targeting of cancer cells. Nuclear factor kappa B (NF-kB) is a regulator for different biological responses, including cell proliferation and differentiation. In acute myeloid leukemia (AML), constitutive NF-κB has been detected in more than 50% of cases, enabling leukemic cells to resist apoptosis and stimulate uncontrolled proliferation. We evaluated NF-kB expression in bone marrow samples from 103 patients with AML using quantitative real time polymerase chain reaction (RT-PCR) and found that expression was increased in 80.5% (83 out 103) of these patients with AML in comparison to the control group. Furthermore, overexpressed transmembrane glycoprotein (CD44) on leukemic cells in comparison to normal cells is known to play an important role in leukemic cell engraftment and survival. We designed poly lactide co-glycolide (PLGA) nanoparticles conjugated with antiCD44 and encapsulating parthenolide (PTL), a nuclear factor kappa B (NF-kB) inhibitor, in order to improve the selectivity and targeting of leukemic cells and to spare normal cells. In vitro, in leukemic cell lines Kasumi-1, KG-1a, and THP-1, proliferation was decreased by 40% (** p < 0.01) with 5 µM PLGA-antiCD44-PTL nanoparticles in comparison to the same concentration of free PTL (~10%). The higher uptake of the nanoparticles by leukemic cells was confirmed with confocal microscopy. In conclusion, PLGA-antiCD44-PTL nanoparticles improved the bioavailability and selective targeting of leukemic cells, thus holding promise as a drug delivery system to improve the cure rate of AML.