Synergistic effect of Zataria Multiflora essential oil on doxorubicin-induced growth inhibition of PC3 cancer cells and apoptosis.

Today, herbs are used as adjuncts to reduce the toxicity of chemotherapy drugs. Here, Zataria-Multiflora Essential Oil (ZEO) was concomitantly employed with doxorubicin, as an anti-cancer drug, to reduce the doxorubicin dosage. The growth inhibition was determined using MTT assay in treated cells. The morphological alteration was observed by fluorescent staining. To verify and compare the apoptosis, AnnexinV-PI flowcytometry and DNA fragmentation assay were performed, and the influence of the compounds on ROS generation was assessed. Changes in MMP and protein expression were analyzed by flowcytometry and western blot, respectively. The results showed that ZEO can act as an amplifier to sensitize PC3 prostate cancer cells to undergo ROS generation and apoptosis. This amplification can heighten the doxorubicin efficacy in lower doses. Consequently, our results indicated that doxorubicin-ZEO combinatory treatment of PC3 cells can reduce the nonspecific toxicity of doxorubicin and can be considered as a candidate in combinatory therapy.

Stabilization of Zataria essential oil with pectin-based nanoemulsion for enhanced cytotoxicity in monolayer and spheroid drug-resistant breast cancer cell cultures and deciphering its binding mode with gDNA.

Efficacy of chemotherapy is limited by the resistance of cancer cells. Phytochemicals especially Essential Oils (EOs) provide an alternative mode of cancer therapy. However, EOs utilization is restricted because of low bioavailability, and high degradation. Nanoemulsification is a method developed to overcome these obstacles. Accordingly, Citrus-Pectin nanoemulsion of Zataria Essential Oil (CP/ZEONE) was prepared to evaluate the anticancer activity and the mechanisms responsible for the caused cytotoxicity. Physical properties and FTIR spectra of CP/ZEONE were characterized. CP/ZEONE progressively improves the suppression of viability of drug-resistant MCF-7, MDA-MB-231 breast cancer cells, and spheroids. It triggers apoptosis by increasing Reactive Oxygen Species (ROS), mitochondrial membrane potential (MMP) loss, DNA damage, G2 and S-phase arrest in MDA-MB-231 cells and spheroids respectively. Additionally, spectroscopy techniques revealed the interaction of CP/ZEONE with DNA via the formation of a groove binding/partial intercalative complex. Thus, ZEO-loaded CP Nano-particles can be further explored as a promising antiproliferative and therapeutic candidate against cancer.

Oxidative DNA damage induced by ROS-modulating agents with the ability to target DNA: A comparison of the biological characteristics of citrus pectin and apple pectin.

DNA targeting anticancer agents have been very successful in clinic, especially, when used in combinatorial therapy. But unfortunately, they often exhibit high levels of toxicity towards normal cells. Hence, much effort has been put into finding agents with more selectivity, and less toxicity. Pectins are natural polysaccharides, and beneficial nutritional fibers that have attracted attentions due to their antitumor properties. However, their molecular targets, and mechanism of action are widely unknown. Here, we have reported that citrus pectin (CP) and apple pectin (AP) selectively suppress viability in MDA-MB-231, MCF-7 and T47D human Breast cancer cells, while non-toxic to L929 normal cells. Upon CP, and AP treatments, cancer cells' ROS content increased rapidly, and led to the collapse of the mitochondrial transmembrane potential which functions upstream of the caspase-dependent apoptosis. CP and AP treated cancer cells were also arrested at the S and G1 or G2/M phases of the cell cycle, respectively. Furthermore, mRNA expression of Galectin-3 (a multi-functional lectin involved in cell adhesion, cell cycle, and apoptosis) reduced in both CP and AP treated cells. Growth inhibition of MDA-MB-231 cells by CP, and AP was concomitant with DNA damage (oxidation, and strand breaks). In this context, in an effort to clarify the mechanism of action, we showed that CP, and AP are able to interact with DNA. The strength and mode of DNA binding were established by spectroscopy techniques. We demonstrated that CP, and AP bind to dsDNA by intercalation, and groove binding/partial intercalation, respectively. In conclusion, our findings suggest that CP, and AP induce apoptosis in MDA-MB-231 cells by increasing the release of ROS, which may be related to the mitochondrial apoptosis pathway, and direct interactions with DNA. Our data indicate that these compounds may be potentially useful in cancer treatment.

Monitoring ZEO apoptotic potential in 2D and 3D cell cultures and associated spectroscopic evidence on mode of interaction with DNA.

Recognizing new anticancer compounds to improve Breast cancer treatment seems crucial. Essential oil of Zataria Multiflora (ZEO) is a secondary metabolite with some biological properties, yet underlying cellular and molecular anticancer properties of ZEO is unclear. GC/MS analysis revealed that carvacrol is the major ingredient of the essential oil. ZEO increasingly suppressed viability in MDA-MB-231, MCF-7 and T47D Breast cancer cells while nontoxic to L929 normal cells in monolayer cell cultures (2D), whereas MDA-MB-231 multicellular spheroids (3D) were more resistant to inhibition. ZEO significantly induced cell apoptosis confirmed by fluorescent staining, flow cytometry analysis and DNA fragmentation in MDA-MB-231 2D and 3D cell cultures. ZEO increased ROS generation and subsequent loss of ΔΨm, caspase 3 activation and DNA damage which consequently caused G1 and G2/M cell cycle arrest in a dose- and time-dependent manner in 2D. S phase arrest occurred in cell spheroids therefore ZEO possible DNA interaction with gDNA was investigated and revealed ZEO binds DNA via intercalation. Altogether, these data corroborate anticancer properties of ZEO and suggest that cell culture format (2D monolayer vs. 3D spheroid) plays a critical role in drug response and provides new insights into the mechanisms underlying ZEO cytotoxicity effect on Breast cancer cells.

Encapsulation of curcumin in diblock copolymer micelles for cancer therapy.

Application of nanoparticles has recently promising results for water insoluble agents like curcumin. In this study, we synthesized polymeric nanoparticle-curcumin (PNPC) and then showed its efficiency, drug loading, stability, and safety. Therapeutic effects of PNPC were also assessed on two cell lines and in an animal model of breast cancer. PNPC remarkably suppressed mammary and hepatocellular carcinoma cells proliferation (P < 0.05). Under the dosing procedure, PNPC was safe at 31.25 mg/kg and lower doses. Higher doses demonstrated minimal hepatocellular and renal toxicity in paraclinical and histopathological examinations. Tumor take rate in PNPC-treated group was 37.5% compared with 87.5% in control (P < 0.05). Average tumor size and weight were significantly lower in PNPC group than control (P < 0.05). PNPC increased proapoptotic Bax protein expression (P < 0.05). Antiapoptotic Bcl-2 protein expression, however, was lower in PNPC-treated animals than the control ones (P < 0.05). In addition, proliferative and angiogenic parameters were statistically decreased in PNPC-treated animals (P < 0.05). These results highlight the suppressing role for PNPC in in vitro and in vivo tumor growth models. Our findings provide credible evidence for superior biocompatibility of the polymeric nanocarrier in pharmacological arena together with an excellent tumor-suppressing response.

Hydrocarbon degradation by thermophilic Nocardia otitidiscaviarum strain TSH1: physiological aspects.

Indigenous thermophilic hydrocarbon degraders are of special significance for the bioremediation of oil-contaminated desert soils with ambient temperature of 45-50 degrees C. The first objective of this study was to demonstrate the hydrocarbon-degrading capability of Nocardia otitidiscaviarum TSH1 (DSM 45,036) which grows optimally at 50 degrees C. Analysis of the metabolic profile of the strain TSH1 showed that it could metabolize phenol, intermediate-chain-length n -alkanes and some polycyclic aromatic hydrocarbons (PAHs) ranging in size from two to four fused rings efficiently, but not toluene and xylene. N. otitidiscaviarum TSH1 was able to survive and grow at phenol concentrations up to 875 mg l(-1). For the first time, the physiological response of a thermophilic Nocardia strain to poorly available hydrophobic compounds was also investigated. When grown on a mineral salt medium with hexadecane, N. otitidiscaviarum TSH1 showed very high affinity for the organic phase. Additionally, PAH-grown cells were considerably hydrophobic. The capacity of PAH-utilizing N. otitidiscaviarum TSH1 isolate to produce biosurfactants was also investigated. Fatty acids (C(14)-C(18)) were detected by GC-MS analysis during bacterial growth in PAH supplemented mineral media. High cell surface hydrophobicity and capability of N. otitidiscaviarum TSH1 to degrade different hydrocarbons at 50 degrees C may make it an ideal candidate to treat oil-contaminated desert soils.