Phytochemical characterization and anti-cancer properties of extract of Ephedra foeminea (Ephedraceae) aerial parts

Purpose: To evaluate the phytochemical profile of methanol extract of Ephedra foeminea and assess its anti-carcer effect on a large set of normal and cancerous cell lines. Methods: Extraction of air-dried powder of aerial parts of E. foeminea was carried out with methanol. The bioactive compounds in the extract were determined using gas chromatography/mass spectrometry (GC-MS). The anti-cancer effect of the extract was determined by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay against various types of normal and cancer cell lines. Serial concentrations of plant extract were used, ranging from 7.812 to1000 μg/mL. Doxorubicin (DOX) served as standard drug. The half-maximal concentration (IC50) values of the extract and DOX for each cell line were determined, and the selectivity index (SI) was computed. Results: Phytochemical analysis showed that the extract contained several bioactive compounds, including alkaloids, flavonoids, sterols and fatty acids. The hazardous ephedra alkaloids (ephedrine and pseudoephedrine) were absent in the plant extract. The extract showed significant anti-proliferative activity against cancer cell lines, when compared with the positive control, doxorubicin (p < 0.05). Selective and concentration-dependent cytotoxicity was exhibited in cancer cell lines of breast (MCF-7), lung (A549), colon (Caco-2), liver (HepG-2) and prostate (PC-3). Weak selectivity was produced in other cancer cell lines, i.e., human epithelioma (Hep-2) and cervical carcinoma (Hela). Interestingly, non-cancerous cells showed no or weak cytotoxicity. Conclusion: Ephedra foeminea exerts potential selectivity in anti-proliferative effect against some cancer cell lines. Thus, it is a promising drug source for the production of new and selective anti-cancer medicines

Targeting Cytochrome P450 Enzymes in Ovarian Cancers: New Approaches to Tumor-Selective Intervention

Over the past decade, there have been significant developments in treatment for ovarian cancer, yet the lack of targeted therapy with few side effects still represents a major issue. The cytochrome P450 (CYP) enzyme family plays a vital role in the tumorigenesis process and metabolism of drugs and has a negative impact on therapy outcomes. Gaining more insight into CYP expression is crucial to understanding the pathophysiology of ovarian cancer since many isoforms are essential to the metabolism of xenobiotics and steroid hormones, which drive the disease’s development. To the best of our knowledge, no review articles have documented the intratumoral expression of CYPs and their implications in ovarian cancer. Therefore, the purpose of this review is to provide a clear understanding of differential CYP expression in ovarian cancer and its implications for the prognosis of ovarian cancer patients, together with the effects of CYP polymorphisms on chemotherapy metabolism. Finally, we discuss opportunities to exploit metabolic CYP expression for the development of novel therapeutic methods to treat ovarian cancer

Glypican-3 Differentiates Intraductal Carcinoma and Paget’s Disease from Other Types of Breast Cancer

Background and Objectives: breast cancer remains the most common health burden affecting females worldwide. Despite developments in breast cancer diagnostic approaches and treatment strategies, the clinical management of metastatic breast cancer remains challenging. Thus, there is a need to identify new biomarkers and novel drug targets for breast cancer diagnosis and therapy. Recently, aberrant glypican-3 (GPC3) expression in cancers has gained considerable interest in cancer research. The studies, however, have yielded contradictory results about GPC3 expression in breast cancer. Therefore, the current study aims to analyse GPC3 expression across a large panel of different breast cancer subtypes. Materials and Methods: GPC3 expression was immunohistochemically evaluated in 230 breast cancer patients along with eight normal tissues and its associations to clinical and demographic characteristics, as well as immunohistochemical biomarkers for breast cancer. Moreover, a public database consisting of breast cancer patients’ survival data and GPC3 gene expression information was used to assess the prognostic value of GPC3 in the survival of breast cancer patients. Results: GPC3 expression was only characterised in 7.5% of different histological breast cancer subtypes. None of the normal breast tissues displayed GPC3 expression. Interestingly, all cases of Paget’s disease, as well as 42.9% of intraductal and 16.7% of mucinous carcinomas were found to have GPC3 expression, where it was able to significantly discriminate Paget’s disease and intraductal carcinoma from other breast cancer subtypes. Importantly, GPC3 expression was found more often in tumours that tested positive for the expression of hormone receptors and human epidermal growth factor receptor 2 (HER2), indicating more favourable histological subtypes of breast cancer. Consequently, longer relapse-free survival (RFS) was significantly correlated with higher GPC3 mRNA expression. Conclusions: Our study proposes that GPC3 is a promising breast cancer subtype-specific biomarker. Moreover, GPC3 may have the potential to be a molecular target for the development of new therapeutics for specific subtypes of breast cancer

Cytochrome 4Z1 Expression Connotes Unfavorable Prognosis in Ovarian Cancers

Background and Objective: Ovarian cancer is a leading cause of death in females. Since its treatment is challenging and causes severe side effects, novel therapies are urgently needed. One of the potential enzymes implicated in the progression of cancers is Cytochrome 4Z1 (CYP4Z1). Its expression in ovarian cancer remains unknown. Therefore, the current study aims to assess CYP4Z1 expression in different subtypes of ovarian cancers. Materials and Methods: Immunohistochemistry was used to characterize CYP4Z1 expression in 192 cases of ovarian cancers along with eight normal ovarian tissues. The enzyme’s association with various clinicopathological characteristics and survival was determined. Results: CYP4Z1 was strongly expressed in 79% of ovarian cancers, compared to negative expression in normal ovarian samples. Importantly, significantly high CYP4Z1 expres-sion was determined in patients with advanced-stage cancer and a high depth of invasion (p < 0.05). Surprisingly, CYP4Z1 expression was significantly associated with a low patient survival rate. Univariate analysis revealed that patient survival was strongly associated with CYP4Z1 expression, tumor stage, depth of invasion, and lymph node metastasis (p < 0.05). Multivariate analysis showed that only CYP4Z1 expression was significantly associated with patient survival (p < 0.05). Conclusions: CYP4Z1 expression is correlated with shorter patient survival and has been identified as an independent indicator of a poor prognosis for ovarian cancer patients