Antitumor Effects of Curcumin on Cervical Cancer with the Focus on Molecular Mechanisms: An Exegesis.

Cervical cancer is one of the most prevalent malignancies among females and is correlated with a significant fatality rate. Chemotherapy is the most common treatment for cervical cancer; however, it has a low success rate due to significant side effects and the incidence of chemo-resistance. Curcumin, a polyphenolic natural compound derived from turmeric, acts as an antioxidant by diffusing across cell membranes into the endoplasmic reticulum, mitochondria, and nucleus, where it performs its effects. As a result, it's been promoted as a chemo-preventive, anti-metastatic, and anti-angiogenic agent. As a consequence, the main goal of the present review was to gather research information that looked at the link between curcumin and its derivatives against cervical cancer.

Curcumin-Based Nanoformulations: A Promising Adjuvant towards Cancer Treatment.

Throughout the United States, cancer remains the second leading cause of death. Traditional treatments induce significant medical toxic effects and unpleasant adverse reactions, making them inappropriate for long-term use. Consequently, anticancer-drug resistance and relapse are frequent in certain situations. Thus, there is an urgent necessity to find effective antitumor medications that are specific and have few adverse consequences. Curcumin is a polyphenol derivative found in the turmeric plant (Curcuma longa L.), and provides chemopreventive, antitumor, chemo-, and radio-sensitizing properties. In this paper, we summarize the new nano-based formulations of polyphenolic curcumin because of the growing interest in its application against cancers and tumors. According to recent studies, the use of nanoparticles can overcome the hydrophobic nature of curcumin, as well as improving its stability and cellular bioavailability in vitro and in vivo. Several strategies for nanocurcumin production have been developed, each with its own set of advantages and unique features. Because the majority of the curcumin-based nanoformulation evidence is still in the conceptual stage, there are still numerous issues impeding the provision of nanocurcumin as a possible therapeutic option. To support the science, further work is necessary to develop curcumin as a viable anti-cancer adjuvant. In this review, we cover the various curcumin nanoformulations and nanocurcumin implications for therapeutic uses for cancer, as well as the current state of clinical studies and patents. We further address the knowledge gaps and future research orientations required to develop curcumin as a feasible treatment candidate.

Development of curcumin-loaded gemini surfactant nanoparticles: Synthesis, characterization and evaluation of anticancer activity against human breast cancer cell lines.

BACKGROUND: Curcumin, the polyphenolic constituent of turmeric, has been recognized as an effective anticancer agent in the treatment of breast cancer. However, the poor bioavailability of curcumin triggers finding of new approaches for elevating its therapeutic efficiency. PURPOSE: We aimed to use gemini surfactant nanocarriers for curcumin in order to overcome its limitations. STUDY DESIGN: We investigated the in vitro characterization of gemini surfactant-curcumin (Gemini-Cur) and examined its antiproliferative & apoptotic activities on breast cancer cell lines. METHODS: Gemini-Cur polymersomes were synthesized through nanoprecipitation method and characterized by dynamic light scattering (DLS), transmission and scanning electron microscopies, HPLC and X-ray diffraction (XRD). The anticancer effect of Gemini-Cur nanoparticles was studied on three different breast cancer cell lines including MCF-7, SkBr-3 and MDA-MB-231 through uptake kinetics, viability & cytotoxicity recordings and apoptotic assays. Furthermore, qRT-PCR was performed to evaluate the expression of apoptotic genes including p16INK4a, p14ARF, Bax and Bcl-2. RESULTS: According to physicochemical analysis, the average particle size, zeta potential value and drug entrapment efficiency for Gemini-Cur compound were recorded as 161 ±â€¯6.2 nm, +5.32 mV and 89.13% ±â€¯0.93, respectively. XRD analysis also confirmed the incorporation of curcumin in gemini surfactant micelles. Regarding the enhanced cellular uptake of sphere shaped Gemini-Cur, our data showed that this nano compound suppresses cancer cell proliferation via induction of apoptosis. Moreover, qRT-PCR analysis revealed that Gemini-Cur could effectively upregulate the expression of p16INK4a, p14ARF and Bax, while significantly decreasing the Bcl-2 expression in these breast cancer cells. CONCLUSION: Our data demonstrates the great potential of gemini surfactants for efficient delivery of curcumin and subsequently, the improvement of its anticancer effect. Therefore, it is sagacious to support the idea that Gemini-Cur nano compound might have the potential to be considered as an anticancer agent.

The anti-proliferative and apoptotic effects of crocin on chemosensitive and chemoresistant cervical cancer cells.

Cervical cancer is the fourth cause of cancer-related mortality among females worldwide. Although current therapies reduce disease symptoms, resistance of tumor cells to chemotherapy agents after a while is a serious problem. Therefore, utilization of novel adjuvant agents to increase efficiency of chemotherapy is essential. In the last two decades, botanicals with effective anticancer activities have been studied. Among them, the anticancer properties of crocin have been more attended. In this study, the molecular mechanism of crocin action was investigated in sensitive human cervical cancer cell line (OV2008) in comparison with the resistant one (C13). A 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) assay showed that crocin inhibits proliferation of sensitive cells (OV2008) at a time- and dose-dependent manner at 48 and 72h. Also, this inhibitory effect has been shown on resistant cells (C13) at 72h. Hoechst staining and flow cytometry assay also confirmed these results and revealed that antiproliferative effect of crocin might be due to the induction of apoptosis. Moreover, the genetic mechanism of crocin-induced apoptosis was accomplished by studying the relative expressions of P53, Bax, Bcl2 and miR-365, an upstream regulator of the last two ones. Real-time PCR analysis indicated that 1.5 and 3mg/ml crocin led to up-regulation of Bax and P53 and down-regulation of Bcl2 and miR-365 at all time intervals in both two cell lines. However, OV2008 cell line was more sensitive to crocin, and alternation of gene expretion was more obvious in this cell line. In this regard, the present study demonstrated the anti-proliferative and apoptotic activities of crocin against both sensitive and resistant cervical cancer cells that may benefit cervical cancer treatment as an adjuvant agent to decrease chemoresistance and increase the efficiency of therapy.

Therapeutic Potential of Novel Nano-Based Curcumin Compounds In Vitro and In Vivo

Despite recent advances in cancer medication, malignant tumors continue to be the second leading cause of death worldwide. Furthermore, introducing a therapeutic compound with low-side effects as well as low-price for consumers is controversial. Recent efforts have been focusing on traditional medicines as a rich source of herbal agents. Curcumin, the major turmeric phytochemical, has been widely assessed as an anti-cancer compound in vitro and in vivo. However, the use of curcumin in cancer treatment has limitations because of its low solubility, poor tissue absorption, rapid metabolism and rapid systemic elimination. Recent work has focused on improving the stability of curcumin to facilitate clinical application. Dendrosomal nano-corcumin (DNC) is one of the most successful compounds showing significant cellular absorption and also anti-tumor effects. The present overview of newest applicable strategies for curcumin-based therapy and their clinical potential usefulness has the emphasis on DNC.

Isolation, spectroscopic characterization, X-ray, theoretical studies as well as in vitro cytotoxicity of Samarcandin.

Samarcandin 1, a natural sesquiterpene-coumarin, was isolated as well as elucidated from F. assa-foetida which has significant effect in Iranian traditional medicine because of its medicinal attitudes. The crystal structure of samarcandin was determined by single-crystal X-ray structure analysis. It is orthorhombic, with unit cell parameters a=10.8204 (5)Å, b=12.9894 (7)Å, c=15.2467 (9)Å, V=2142.9 (2)Å(3), space group P212121 and four symmetry equivalent molecules in the unit cell. Samarcandin was isolated in order to study for its theoretical studies as well as its cellular toxicity as anti-cancer drug against two cancerous cells. In comparison with controls, our microscopic and MTT assay data showed that samarcandin suppresses cancer cell proliferation in a dose-dependent manner with IC50=11µM and 13 for AGS and WEHI-164 cell lines, respectively. Density functional theory (DFT) and time-dependent density functional theory (TD-DFT) of the structure was computed by three functional methods and 6-311++G(∗∗) standard basis set. The optimized molecular geometry and theoretical analysis agree closely to that obtained from the single crystal X-ray crystallography. To sum up, the good correlations between experimental and theoretical studies by UV, NMR, and IR spectra were found.

Biochemical and biophysical properties of a novel homoisoflavonoid extracted from Scilla persica HAUSSKN.

In this study isolation and structural elucidation of a homoisoflavonoid, 3-(3',4'-dihydroxybenzyl)-8-hydroxy-5,7-dimethoxychroman-4-one (Scillapersicone 1), is reported from Scilla persica HAUSSKN. The structure was solved by a single crystal X-ray analysis. The unit cell parameters are a=11.7676 (2)Å, b=20.1174 (4)Å, c=7.8645 (9)Å, ß=93.544 (2)°, V=1858.23 (7)Å(3), monoclinic space group P21/c and four symmetry equivalent molecules in an unit cell. The structure was consistent with the UV, IR, 1D and 2D NMR, HRFAB-MS data. The optimized molecular geometry agrees closely that obtained from the single crystal X-ray crystallography. Furthermore, cytotoxicity of this compound was evaluated by MTT assay on AGS and WEHI-164 cancerous cell lines.

Dendrosomal curcumin significantly suppresses cancer cell proliferation in vitro and in vivo.

Curcumin, the main compound of spice turmeric, is one of the natural products that has been shown to possess effective anti-cancer properties. However, the absorption efficacy of curcumin is too low to make dramatic results in therapy. Therefore, we based the main aim of this study on improving the bioavailability of curcumin taking advantage of dendrosome nanoparticles; and subsequently evaluating in vitro and in vivo anti-tumor properties of dendrosomal curcumin. In vitro studies were carried out utilizing A431 and WEHI-164 cell lines and mouse embryonic normal fibroblasts. Our data revealed that dendrosomal curcumin not only exhibits a much higher bioavailability than void curcumin (P<0.05) but also inhibits the proliferation of cancer cells (P<0.01) in a time- and dose-dependent manner that could be ascribed to the induction of apoptosis. However, dendrosome did not indicate any toxic effect on different types of cell lines. For in vivo studies, BALB/c tumor-bearing mice were treated with dendrosomal curcumin, void curcumin, dendrosome and PBS. The results indicated that dendrosomal curcumin reduces significantly the tumor size in comparison with void curcumin and control samples (P<0.05). Furthermore, in animals treated with dendrosomal curcumin a longer survival was observed (P<0.01). We also found that the mice treated with dendrosomal curcumin, showed a significant increase in splenocyte proliferation and IFN-γ production as well as a significant decrease in IL-4 production. This can be a proof of anti-tumor immunity caused by dendrosomal curcumin. The findings demonstrate that dendrosomal curcumin offers a great potential to be a promising anti-cancer therapeutic agent.