Cytotoxic and apoptogenic effect of hypericin, the bioactive component of Hypericum perforatum on the MCF-7 human breast cancer cell line.

BACKGROUND: Breast cancer is the most prevalent malignancies among the women that have a high mortality. Previous studies demonstrated that hypericin, a bioactive component of Hypericum perforatum have a cytotoxic effect on the malignant cell lines. However, an anti-carcinogenic activity of hypericin on MCF-7 is uncertain. To investigate the cytotoxic effect of hypericin on MCF-7 cells, a human breast adenocarcinoma cell-line, that resistance to chemotherapy. METHODS: The MCF-7 and fibroblast (as normal cell line) were treated with various concentrations of hypericin, and Cisplatin as a positive control for 24 and 48 h. Cytotoxicity activity was measured and confirmed by MTT assay and Trypan blue staining, respectively. In addition, Apoptosis were determined by Annexin V/Propidium Iodide assay. Immunocytochemistry (ICC) analysis for bcl2 and p53 proteins performed to further investigate different expression of these genes in different samples. RESULTS: Both cisplatin and the hypericin exhibited a dose-dependent cytotoxic effect in the MCF-7 cell line. Although the LD50 of the hypericin was significantly lower when compared to cispaltin (5 vs. 20 µg/ml), it continued to decrease the growth rate of the MCF-7 cells when tested at higher concentration than LD50. In contrast, cisplatine, at higher concentration than LD50, completely inhibited the growth of the MCF-7 in 48 h. Regarding Annexin V/Propidium results, treatment of MCF-7 cells with LD50 concentration of cisplatin and hypericin showed 60 and 52 % apoptosis in 24 h, respectively. ICC analysis for bcl2 and p53 also confirmed our results; in treated samples for the dose of LD50 in 24 and 48 h of cisplatin and hypercin, more cells expressed p53 (guardian of cells in front of tumor formation/progression) and less expressed bcl2 (which has anti apoptotic activity) compared to untreated samples. CONCLUSIONS: Considering that hypericin showed to be cytotoxic, it seems to be a chemopreventive agent and a good candidate for antineoplastic drug development.

Differentiating Primary and Recurrent Lesions in Patients with a History of Breast Cancer: A Comprehensive Review.

Breast cancer (BC) recurrence remains a concerning issue, requiring accurate identification and differentiation from primary lesions for optimal patient management. This comprehensive review aims to summarize and evaluate the current evidence on methods to distinguish primary breast tumors from recurrent lesions in patients with a history of BC. Also, we provide a comprehensive understanding of the different imaging techniques, including mammography, ultrasound, magnetic resonance imaging, and positron emission tomography, highlighting their diagnostic accuracy, limitations, and potential integration. In addition, the role of various biopsy modalities and molecular markers was explored. Furthermore, the potential role of liquid biopsy, circulating tumor cells, and circulating tumor DNA in differentiating between primary and recurrent BC was emphasized. Finally, it addresses emerging diagnostic modalities, such as radiomic analysis and artificial intelligence, which show promising potential in enhancing diagnostic accuracy. Through comprehensive analysis and review of the available literature, the current study provides an up-to-date understanding of the current state of knowledge, challenges, and future directions in accurately distinguishing between primary and recurrent breast lesions in patients with a history of BC.

Cyanidin 3-glycoside induced apoptosis in MCF-7 breast cancer cell line.

Introduction: Breast cancer is the major leading cause of death from cancer among women. Given the drug resistance seen during the treatment of this disease, it is very important to identify new therapies and new anticancer drugs. Some studies indicate the cytotoxic effects of cyanidin 3-glycoside (C3G). Therefore, this study aims to evaluate the anticancer effect of C3G in the treatment of the MCF-7 cell line. Material and methods: In this study, the MCF-7 cell line was treated with different concentrations of C3G for 24 and 48 h. Assessment of cell death was performed by MTT assay. The cell apoptosis rate was measured using an Annexin V/propidium iodide assay through flow cytometry. The expression levels of p53, Bax, Caspase3, CYP1, CYP2, and Bcl2 genes were evaluated using polymerase chain reaction, and Western blotting was performed for CYP1 to confirm the results. Results: Our findings showed that C3G has dose-dependent cytotoxic effects on the MCF-7 cell line. According to flow cytometry results, the apoptosis of the cells 24 h after exposure to C3G was more than 51.5%. Moreover, after 24 h of exposure to the half-maximal inhibitory concentration of C3G, the expression of p53, Bax, Caspase3, CYP1, and CYP2 genes increased, and the expression of Bcl2 gene decreased. The Western blotting showed that CYP1 protein increased 2-fold compared to the control sample. Conclusions: The results of this study demonstrated that C3G has apoptotic and cytotoxic effects on breast cancer cells. Therefore, it is likely that this substance could be a suitable option for cancer therapy.

Cytotoxic and Apoptotic Effects of Vanadyl Sulfate on MCF-7 Breast Cancer Cell Line.

BACKGROUND: Breast cancer (BC) is the major cause of cancer-related death in women. Some studies have indicated the cytotoxic effects of vanadyl oxide sulfate (VOSO4). This study aimed to evaluate the anti-cancer effect of VOSO4 in the treatment of MCF-7 cell lines. MATERIALS AND METHODS: The MCF-7 cell line was treated with different concentrations of VOSO4 for 24 and 48 hours. Cell death was measured using the MTT assay. The cell apoptosis rate was measured using Annexin V/Propidium Iodide assay through flow cytometry. Also, the expression levels of p53, P21, Caspase8, superoxide dismutase type 1 (SOD1), Sod2, and Bcl2 mRNAs were assessed, and Western blotting was performed for Sod1 protein. RESULTS: The results showed that the half-maximal inhibitory concentration (IC50) for VOSO4 was 25 and 20 µg/ml for 24 and 48 hours, respectively. Indeed, VOSO4 has dose-dependent cytotoxic effects on the MCF-7. Also, after exposure to VOSO4 for 24 hours, cell apoptosis reached 52% compared with untreated cells. Moreover, after 24 hours of exposure to VOSO4 with IC50 concentration, the expression of p53, P21, Caspase8, Sod1, and Sod2 mRNAs increased (P0.05), and the expression of Bcl2 mRNA was decreased (P0.05). Also, the Western blotting revealed Sod1 protein level markedly increased following exposure to VOSO4 (P0.05). CONCLUSION: Our results demonstrated that VOSO4 has an apoptotic and cytotoxic effect on BC cells. Therefore, it could be considered a complementary agent for the medical treatment of patients with BC.

Antioxidant and Anti-Inflammatory Effects of Coenzyme Q10 on L-Arginine-Induced Acute Pancreatitis in Rat.

This study was aimed at evaluating the protective effect of coenzyme Q10 on L-arginine-induced acute pancreatitis in rats regarding biomarkers and morphologic changes. Thirty-two male Sprague-Dawley rats were divided into 4 equal groups. Control group received intraperitoneal normal saline, while in sham and experimental groups 1 and 2 pancreatitis was induced with L-arginine. E1 and E2 groups were treated with a single dose of 100 and 200 mg/kg Q10, respectively. Serum lipase and amylase, along with pancreas IL-10, IL-1ß, and TNF-α, were measured. For evaluation of oxidative stress, pancreatic superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA), and myeloperoxidase (MPO) were assessed. Histopathological examination for morphologic investigation was conducted. Serum amylase and lipase, as well as TNF-α and IL-1ß cytokines, reverted with administration of Q10 in consistence with dosage. In contrast, Q10 assisted in boosting of IL-10 with higher dosage (200 mg/kg). A similar pattern for oxidative stress markers was noticed. Both MDA and MPO levels declined with increased dosage, contrary to elevation of SOD and GSH. Histopathology was in favor of protective effects of Q10. Our findings proved the amelioration of pancreatic injury by Q10, which suggest the anti-inflammatory and antioxidant property of Q10 and its potential therapeutic role.

A Review of the Clinical Implications of Breast Cancer Biology.

BACKGROUND: Histologically similar tumors may have different prognoses and responses to treatment. These differences are due to molecular differences. Hence, in this review, the biological interaction of breast cancer in several different areas is discussed. In addition, the performance and clinical application of the most widely-recognized biomarkers, metastasis, and recurrences from a biological perspective and current global advances in these areas are addressed. OBJECTIVE: This review provides the performance and clinical application of the most widely-recognized biomarkers, metastasis, and recurrences from the biological perspective and current global advances in these areas. METHODS: PubMed, Scopus, and Google Scholar were searched comprehensively with combinations of the following keywords: "breast cancer," "biological markers," and "clinical." The definition of breast cancer, diagnostic methods, biological markers, and available treatment approaches were extracted from the literature. RESULTS: Estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER-2), and Ki-67 are the most well-known biological markers that have important roles in prognosis and response to therapeutic methods. Some studies showed the response of ER-positive and PR-negative tumors to anti-estrogenic treatment to be lower than ER-positive and PR-positive tumors. Patients with high expression of HER-2 and Ki-67 had a poor prognosis. In addition, recent investigations indicated the roles of new biomarkers, such as VEGF, IGF, P53 and P21, which are associated with many factors, such as age, race, and histological features. CONCLUSION: The objective of scientists, from establishing a relationship between cancer biology infrastructures with clinical manifestations, is to find new ways of prevention and progression inhibition and then possible introduction of less dangerous and better treatments to resolve this dilemma of human society.

Comparison of in Vitro Cytotoxicity and Apoptogenic Activity of Magnesium Chloride and Cisplatin as Conventional Chemotherapeutic Agents in the MCF-7 Cell Line.

Breast cancer is the most common malignancy and also the second leading cause of cancer death among women and also in women that have a high mortality. Previous studies showed that magnesium (Mg) has cytotoxic effects on malignant cell lines. However, the anti-cancer effects of Mg on MCF-7 breast cancer cells are uncertain. This study was aimed at the comparison of the cytotoxic effect of Mg salt (MgCl2) and cisplatin on MCF-7 cells and fibroblasts (as normal cells). After treatment with various concentrations of MgCl2, and cisplatin as a positive control for 24 and 48 hours (h), cytotoxicity activity was measured by MTT assay. In addition, apoptosis was determined by annexin V/propidium iide assay. Both cisplatin and the MgCl2 exhibited dose-dependent cytotoxic effects in the MCF-7 cell line, although the LD50 of the Mg was significantly higher when compared to cispaltin (40 µg/ml vs. 20 µg/ml). Regarding annexin V/propidium results, treatment of MCF-7 cells with LD50 concentrations of cisplatin and Mg showed 59% and 44% apoptosis at 24h, respectively. Finally, the results indicated that Mg has cytotoxic effects on MCF-7 cells, but less than cisplatin as a conventional chemotherapeutic agent. However, regarding the side effects of chemotherapy drugs, it seems that Mg can be considered as a supplement for the treatment of breast cancer.

Prevalence of HER-2 and Hormone Receptors and P53 Mutations in the Pathologic Specimens of Breast Cancer Patients.

Prognostic factors are in interest for breast cancer as the second cause of malignancy deaths. Some have predictive values as human epidermal growth factor receptor-2 (HER-2) and estrogen receptor (ER). To access the incidence of HER2 and its relations to other factors, like age, pathology, ER, progesterone receptor (PR), and P53, 2000 pathologic blocks from 2750 total samples have been selected from 2011 to 2013 in Cancer Institute of Tehran. Incidence of HER2, ER, PR, and P53 was; 58.5%, 33.4%, 43.3%, and 65.4%, respectively. Invasive ductal carcinoma was the most pathologic type (82.2%) and 60%-70% positive HER2 and P53 had negative ER and PR (poor prognosis). The peak age of incidence of breast cancer was perimenopausal age group (46-55 years). Our cases had more positive HER2 and P53 and less positive PR and ER compared to other studies. High perimenopausal incidence as another finding assures the importance of breast cancer screening in these age groups.