The Antioxidant and anti-inflammatory Activity of Selenium and Lecithin Combination Against ethanol-induced Gastric Ulcer in mice via Modulating IGF-1/PTEN/Akt/FoxO3a Signaling.

Gastric ulcers are one of the most prevalent gastrointestinal disorders. The current study investigated the antioxidant and anti-inflammatory effects of selenium (Se) and lecithin (Lec) alone and in combination against ethanol-induced gastric ulcers in mice, and their ability to modulate insulin-like growth factor-1 (IGF-1)/ Phosphatase and tensin homologue deleted on chromosome 10 (PTEN)/ Protein kinase B (Akt)/ Forkhead box O3a (FoxO3a) signaling. The mice were divided into normal, ethanol, Se + ethanol, Lec + ethanol, Se + Lec + ethanol, and omeprazole + ethanol groups. Treatment with the selected doses was continued for 14 days before a single dose of absolute ethanol (5 ml/kg body weight) was administered to induce gastric ulcers in mice. The results showed that pretreatment with Se and Lec combination effectively decreased both the macro- and microscopic gastric lesions and increased the protection index compared to the ethanol group. Remarkably, the Se and Lec combination decreased the levels of reactive oxygen species, malondialdehyde, and cytochrome c and increased glutathione, glutathione peroxidase, and thioredoxin reductase activities in gastric tissues. The Se and Lec combination increased prostaglandin E2 and interleukin-10 levels but decreased tumor necrosis factor-α, interleukin-6 and interleukin-1ß levels compared to either treatment alone. Interestingly, this combination decreased the expression of IGF-1, p-Akt, and FoxO3a proteins and increased PTEN expression in gastric tissues. The gastric tissues examination by hematoxylin and eosin staining confirmed these results. Therefore, the Se and Lec combination showed superior protective effects against ethanol-induced gastric ulcers in mice, compared to either treatment alone, through antioxidant, and anti-inflammatory activities, in addition to modulating IGF-1/PTEN/Akt/FoxO3a pathway signaling.

Correction: Youssef et al. Phytochemical Analysis and Profiling of Antitumor Compounds of Leaves and Stems of Calystegia silvatica (Kit.) Griseb. Molecules 2023, 28, 630.

There were errors in the original publication [...].

Phytochemical Analysis and Profiling of Antioxidants and Anticancer Compounds from Tephrosia purpurea (L.) subsp. apollinea Family Fabaceae.

Tephorosia purpurea subsp. apollinea was extracted with methanol and n-hexane to obtain sub-fractions. The chemical compounds identified with GC-MS and HPLC in T. purpurea subsp. apollinea extracts showed antioxidant and anticancer properties. The antioxidant and anticancer activities were investigated using DDPH and ABTS assays, and MTT assay, respectively. Stigmasta-5,24(28)-dien-3-ol, (3 ß,24Z)-, 9,12,15-octadecatrienoic acid methyl ester, phytol, chlorogenic acid, and quercetin were the major chemical compounds detected in T. purpurea subsp. apollinea. These compounds possessed antioxidant and anticancer properties. The methanol extract showed antioxidant properties with DDPH and ABTS radical scavenging of 84% and 94%, respectively, relative to ascorbic acid and trolox. The anticancer effects of T. purpurea subsp. apollinea against the cancer cell lines MCF7 (IC50 = 102.8 ± 0.6 µg/mL), MG63 (IC50 = 118.3 ± 2.5 µg/mL), T47D (IC50 = 114.7 ± 1.0 µg/mL), HeLa (IC50 = 196.3 ± 2.3 µg/mL), and PC3 (IC50 = 117.7 ± 1.1 µg/mL) were greater than its anticancer effects against U379 (IC50 = 248.4 ± 7.5 µg/mL). However, it had no adverse effects on the normal cells (WI38) (IC50 = 242.9 ± 1.8 µg/mL). Therefore, the major active constituents presented in T. purpurea subsp. apollinea can be isolated and studied for their potential antioxidant and anticancer effects against breast, cervical, and prostate cancers and osteosarcoma.

Phytochemical Analysis and Profiling of Antitumor Compounds of Leaves and Stems of Calystegia silvatica (Kit.) Griseb.

Anti-tumor compounds from natural products are being investigated as possible alternatives for cancer chemotherapeutics that have serious adverse effects and tumor resistance. Calystegia silvatica was collected from the north coast of Egypt and extracted via methanol and n-hexane sub-fraction. The biologically active compounds of Calystegia silvatica were identified from the methanol and n-hexane extracts from the leaves and stems of the plant using GC-MS and HPLC. The antitumor properties of both parts of the plant were investigated against cancer and non-cancer cell lines using the MTT assay, and the IC50 in comparison to doxorubicin was calculated. The main compounds identified in the methanol extract were cis-vaccenic acid and trans-13-octadecenoic acid in the leaves and stems, respectively, and phenyl undecane and 3,7,11,15 tetramethyl-2-hexadeca-1-ol in the n-hexane extracts of the leaves and stems, respectively. Both parts of the plant contained fatty acids that have potential antitumor properties. The methanol extract from the stems of C. silvatica showed antitumor properties against HeLa, with an IC50 of 114 ± 5 µg/mL, PC3 with an IC50 of 137 ± 18 µg/mL and MCF7 with an IC50 of 172 ± 15 µg/mL, which were greater than Caco2, which had an IC50 of 353 ± 19 µg/mL, and HepG2, which had an IC50 of 236 ± 17 µg/mL. However, the leaf extract showed weak antitumor properties against all of the studied cancer cell lines (HeLa with an IC50 of 208 ± 13 µg/mL, PC3 with an IC50 of 336 ± 57 µg/mL, MCF7 with an IC50 of 324 ± 17 µg/mL, Caco2 with an IC50 of 682 ± 55 µg/mL and HepG2 with an IC50 of 593 ± 22 µg/mL). Neither part of the plant extract showed any cytotoxicity to the normal cells (WI38). Therefore, C. silvatica stems may potentially be used for the treatment of cervical, prostate and breast cancer.

Phytochemistry and Anticancer Effects of Mangrove (Rhizophora mucronata Lam.) Leaves and Stems Extract against Different Cancer Cell Lines.

The biologically active components of the methanol extracts of R. mucronata were identified using GC/MS. The anticancer effects of each methanol extract from the leaves and stem were evaluated against cancer and non-cancer cell lines. The MTT assay was used in order to evaluate cell viability, and the IC50 and the selectivity indices were calculated in relation to a positive control (doxorubicin). The results showed that 11 and 8 different chemical compounds were found in the methanol extracts from the leaves and stems of R. mucronata, respectively. The active constituents of R. mucronata leaves and stems had anticancer effects against colon cancer (CaCo-2), with IC50 levels of 127 ± 4 µg/mL and 107 ± 6 µg/mL, respectively, and on breast cancer (MCF-7), with IC50 levels of 158 ± 10 µg/mL and 138 ± 4 µg/mL, respectively. These were both greater than their effects on prostate cancer (PC-3), for which they showed IC50 levels of 480 ± 14 µg/mL and 294 ± 3 µg/mL, respectively. However, the anticancer effect of the stems on lung cancer (A549) (IC50 = 155 ± 10 µg/mL) was greater than that of the leaves (IC50 = 376 ± 9 µg/mL) in comparison with doxorubicin. Neither the stems nor the leaves of R. mucronata showed any cytotoxicity against normal cells (WI-38), with the IC50 being 932 ± 30 µg/mL for the leaves and 629 ± 3 µg/mL for the stems.

Cytochrome 4Z1 Expression is Associated with Poor Prognosis in Colon Cancer Patients.

PURPOSE: Colon cancer is a leading cause of mortality worldwide. It has a relatively poor prognosis; therefore, new therapies are needed. One of the tumour-related enzymes that has gained considerable interest is CYP4Z1. This enzyme has been expressed in many tumours and has been hypothesized as a potential biomarker or target for novel anticancer therapies. PATIENTS AND METHODS: CYP4Z1 overexpression was immunohistochemically examined in a large panel of colon tissue types including normal, benign, primary and metastatic ones, and the enzyme's relation to histopathological features and patient survival was evaluated. RESULTS: A high CYP4Z1 expression was observed in benign, primary and metastatic colon tissues compared to a weak or lack of expression in normal tissues. Importantly, there was a significant differential in CYP4Z1 expression where it was stronger in metastatic, primary and benign, respectively (p < 0.05). A significantly high rate of CYP4Z1 expression was found in high histological grades and late stages of the disease, where its expression was more evident in patients with metastasis in the lymph nodes (p < 0.05). Interestingly, CYP4Z1 expression was identified an independent prognostic predictor of poor overall survival of colon cancer patients (p = 0.003). CONCLUSION: CYP4Z1 was distinctly overexpressed in benign, primary and metastatic colon tissues compared to corresponding normal tissues. This differential in CYP4Z1 expression across different types of colon tissues strongly supports CYP4Z1 as potential biomarker and target for novel anticancer therapy development.

Cytochrome P450 1B1 Overexpression in Cervical Cancers: Cross-sectional Study.

BACKGROUND: Current standard treatments for patients with recurrent cervical cancer are not very effective and are associated with severe toxicity. Recently, the rational approach for the discovery of new therapies for cervical cancer is based on the alterations in the molecular biology of cancer cells. One of the emerging molecular changes in cancer cells is the aberrant expression of cytochrome P450 1B1 (CYP1B1). This unique enzyme has been reported to be selectively overexpressed in several cancers. OBJECTIVE: The aim of this study was to examine CYP1B1 expression in cervical cancers and to assess the enzyme's relationship with several clinicopathological features. METHODS: Immunohistochemistry was performed to examine CYP1B1 expression in 100 patient samples with cervical cancer and 10 patient samples with normal healthy cervical tissues. RESULTS: CYP1B1 was expressed in the majority of the cervical cancer samples (91/100, 91.0%) but not in normal healthy cervical samples. The difference in the expression of CYP1B1 between healthy and tumorous cervical tissues was significant (P=.01). Moreover, the frequency of CYP1B1 expression was found to be significantly higher in patients with advanced grades of the disease (P=.03) and in patients having metastasis to the lymph nodes (P=.01). Surprisingly, there was a significantly higher expression of CYP1B1 in patients with a high prevalence of human papilloma virus 16/18 (P=.04). CONCLUSIONS: The differential profile of CYP1B1 expression between cervical cancer tissues and normal cervical tissues suggests that CYP1B1 may be used as a target for future therapeutic exploitations.

Cytochrome 4Z1 Expression is Associated with Unfavorable Survival in Triple-Negative Breast Cancers.

PURPOSE: Triple-negative breast cancer (TNBC) is characterized by high mortality rate, and its clinical management is difficult and complex. Therefore, there is a need for extensive efforts aimed at accelerating the discovery of novel therapies for TNBC. CYP4Z1 has been implicated in the development of breast cancer. The current study aimed at characterizing the expression of CYP4Z1 on TNBC. MATERIALS AND METHODS: Using immunohistochemistry, CYP4Z1 expression was evaluated on 122 TNBC samples, four samples of breast cancers expressing ER, PR, and HER-2, and four samples of normal breast tissues. The association between the enzyme and various histopathological features and survival of patients were determined. RESULTS: CYP4Z1 was strongly expressed in 83.3% of various histopathological subtypes of TNBC, when compared to negative expression in normal breast tissues. Interestingly, there were marked variations in CYP4Z1 expression with respect to histopathology subtype, histological grade, histological stage and tumor diameter. There was a high incidence of CYP4Z1 expression in patients with advanced grades, late stages and larger tumor sizes. Importantly, CYP4Z1 expression was correlated with the survival of TNBC patients, but it was an independent determinant of the poor prognosis of TNBC (p< 0.05). CONCLUSION: CYP4ZI may be a potential biomarker or target for evolving new CYP4Z1-targeted treatments.

Cytochrome 4Z1 Expression Is Correlated with Poor Prognosis in Patients with Cervical Cancer.

BACKGROUND: cervical cancer is one of the most common malignancies in women worldwide and its management remains challenging and complex. As Cytochrome4Z1 (CYP4Z1) is overexpressed in many tumours, its expression in cervical cancer is unknown. Therefore, the present study aimed to evaluate CYP4Z1 expression in cervical cancers. METHODS: CYP4Z1 expression was immunohistochemically assessed in 100 cases of cervical cancers along with ten normal cervix tissues, and the enzyme's relationship to several clinicopathological features and survival was explored. RESULTS: CYP4Z1 was strongly expressed in 55% of cervical cancer patients. Normal cervix samples were negative for CYP4Z1 expression. Importantly, this expression was significantly found in patients with the late stage of the disease, lymph node metastasis, and high tumour invasion (p < 0.05). Interestingly, CYP4Z1 expression was significantly correlated with shorter survival times of cervical cancer patients. Univariate analysis showed that CYP4Z1 expression, tumour stage, lymph node metastasis, and tumour invasion were significantly correlated with patient survival (p < 0.05). The multivariate analysis revealed that only CYP4Z1 expression and tumour stage were significantly correlated with patient survival (p < 0.05). CONCLUSIONS: CYP4Z1 expression is associated with cervical cancer patients' survival and may serve as an independent predictor of poor prognosis in cervical cancer patients.

Glypican-1 Overexpression in Different Types of Breast Cancers.

PURPOSE: Treatment of metastatic breast cancer patients is challenging and remains a major underlying cause of female mortality. Understanding molecular alterations in tumor development is critical to identify novel biomarkers and targets for cancer diagnosis and therapy. One of the aberrant cancer expressions gaining recent research interest is glypican-1. Several studies reported strong glypican-1 expression in various types of human cancers. However, none of these investigated glypican-1 expression in a large cohort of breast cancer histopathological subtypes. PATIENTS AND METHODS: Immunohistochemistry was used to assess glypican-1 expression in 220 breast cancer patients and its relation to demographic and clinical features, as well as important prognostic immunohistochemical markers for breast cancer. RESULTS: Intense glypican-1 expression was recognized in all breast cancer histopathological subtypes. Normal, healthy breast tissue displayed a heterogeneous low expression (20%). Importantly, a strong differential in glypican-1 expression was determined between normal and malignant breast tissues. Moreover, there was a significantly high rate of glypican-1 expression in advanced grades of breast cancer patients and larger tumor sizes. Unfortunately, the glypican-1 expression demonstrated no obvious relationship with the expression of various biomarkers in breast cancer. CONCLUSION: This study may establish glypican-1 as a promising new therapeutic target for the development of therapy in breast cancer.

Profiling of CYP4Z1 and CYP1B1 expression in bladder cancers.

Bladder cancer is the tenth most common cancer worldwide, where its burden remains a challenge and needs new novel therapies. Several reports indicate expression of CYP4Z1 and CYP1B1 in many tumours. Their expressions are associated with a poor prognosis, and therefore proposed as promising biomarkers or targets for anticancer therapy. By using immunohistochemistry, expression of CYP4Z1 and CYP1B1 was evaluated in a panel of different types of bladder cancer, and the enzymes' relation to histopathological features were assessed. Results showed an increased expression of CYP4Z1 (54.3%) and CYP1B1 (76.9%) in the majority of bladder cancers compared to weak or lack of expression of both enzymes in normal tissues. CYP4Z1expression was significantly associated with tumour grade and stage where the expression was markedly increased in a high grade and advanced stage of the disease (p < 0.05). Additionally, CYP1B1 expression was also associated with TNM staging (p < 0.05) and its expression was increased in patients with lymph node metastasis. The expression profiles of CYP4Z1 and CYP1B1 suggest that both enzymes have the potential to be biomarkers or targets for novel anticancer therapy for bladder cancer. Nevertheless, further studies are needed to better delineate whether these enzymes are druggable targets.