Cytotoxic and pro-apoptotic Effects of Spirulina Platensis Extract on PC-3 Prostate Adenocarcinoma Cell Line

Introduction: Prostate cancer is one of the most common cancers among men, with an increasing incidence and mortality rate. In the present study, cytotoxic and pro-apoptotic effects of spirulina platensis extract on PC-3 prostate adenocarcinoma cell line were investigated. Methods: In the present experimental study, the PC-3 prostatic cancer cells were treated in four experimental with 400, 200, 100 and 50 μg / ml extract of spirulina and incubated at 24 and 48 hours. Cytotoxicity was analyzed by MTS kit (3-(4, 5-Dimethylthiazol-2-yl)-5-(3-Carboxymethoxyphenyl)-2-(4-Sulfophenyl)-2H-Tetrazolium, Inner Salt) and apoptosis was analyzed by flow- cytometry using an Annexin V-FITC/PI kit according to the manufacturer protocol in both times. Statistical analysis was accomplished by ANOVA and Duncan tests using FlowJo and SPSS 16 software. Results: In the experimental groups treated with extract of spirulina, the viability of the cells showed a decrease compared to control group, while this decrease was more noticeable in the experimental group of 100 μg / ml at both incubation times (<0.0071).Increased incidence of apoptosis was significantly higher in the experimental groups than the control group. However, this increase was significantly higher than the control group at concentrations of 200 μg / ml in 24h incubation time (Ƥ < 0.0331) and 100 μg / ml of 48h incubation time (Ƥ < 0.0502). Conclusion: Extract of Spirulina at specific concentrations reduced cell growth and induced apoptosis in PC-3 prostatic cancer cells. Evidence suggests that spirulina can be used as an anticancer drug for the treatment of prostate cancer.

Role of HMGB1 in Cisplatin-Persistent Lung Adenocarcinoma Cell Lines

Significant advances have been made recently in the development of targeted therapy for lung adenocarcinoma. However, platinum-based chemotherapy remains as the cornerstone in the treatment of this neoplasm. This is the treatment option for adenocarcinomas without EGFR gain-of-function mutations or tumors that have developed resistance to targeted therapy. The High-Mobility Group Box 1 (HMGB1) is a multifunctional protein involved in intrinsic resistance to cisplatin. HMGB1 is released when cytotoxic agents, such as cisplatin, induce cell death. In the extracellular milieu, HMGB1 acts as adjuvant to induce an antitumor immune response. However, the opposite effect favoring tumor progression has also been reported. In this study, the effects of cisplatin in lung adenocarcinoma cell lines harboring clinically relevant mutations, such as EGFR mutations, were studied. Subcellular localization of HMGB1 was detected in the cell lines and in viable cells after a single exposure to cisplatin, which are designated as cisplatin-persistent cells. The mRNA expression of the receptor for advanced glycation end products (RAGE), TLR-2, and TLR-4 receptors was measured in parental cell lines and their persistent variants. Finally, changes in plasma HMGB1 from a cohort of lung adenocarcinoma patients without EGFR mutation and treated with cisplatin-based therapy were analyzed. Cisplatin-susceptible lung adenocarcinoma cell lines died by apoptosis or necrosis and released HMGB1. In cisplatin-persistent cells, nuclear relocalization of HMGB1 and overexpression of HMGB1 and RAGE, but not TLR-2 or TLR-4, were observed. In tumor cells, this HMGB1–RAGE interaction may be associated with the development of cisplatin resistance. The results indicate a direct relationship between the plasma levels of HMGB1 and overall survival. In conclusion, HMGB1 may be an effective biomarker associated with increased overall survival of lung adenocarcinoma patients.

The Human Positive Cofactor 4 is a Promising Chemotherapeutic Target in Lung Adenocarcinoma

Reduced sensitivity to chemotherapeutic drugs is almost inevitable in lung adenocarcinoma patients. Thus, understanding the relevant mechanisms is urgent. Positive cofactor 4 (PC4) was at first revealed to be a coactivator of basal transcription. Previous research has shown that PC4 participates in various cellular processes in normal and malignant cells. However, it is still unknown whether PC4 participates in altering the lung adenocarcinoma cell sensitivity to chemotherapy, and the relevant mechanisms remain to be explained. In this study, we discovered that PC4 was overexpressed in cisplatin-resistant lung adenocarcinoma cells. PC4 decreased cisplatin’s cytotoxic effects on lung adenocarcinoma in vivo and in vitro. Furthermore, PC4 positively correlated with SOX9 in multiple cancers. PC4 was an upstream regulator of SOX9 in lung adenocarcinoma. Furthermore, PC4 mediated lung adenocarcinoma cell sensitivity to the HIF-PH inhibitor DMOG and the mTOR inhibitor rapamycin, and PC4 mediated the synergistic effect of DMOG and cisplatin. Finally, PC4 destabilized HIF-1α upon cisplatin treatment. Our research showed that PC4 participates in mediating lung adenocarcinoma cell sensitivity to multiple drugs. Mechanistically, PC4 governs multiple downstream pathways associated with chemotherapy resistance, including the SOX9 and HIF-1α pathways. Thus, PC4 is a promising chemotherapeutic target in lung adenocarcinoma.

Synthesis, Characterization and Biological Evaluation of Novel Triazolyl - Acridine Derivatives as Cytotoxic Agents

Acridine and Triazols both are biologically active heterocyclic rings with cytotoxic potential. Triazolyl- acridine adduct attract the attention in the field of medicinal chemistry. Here we synthesized a series of triazolyl- acridine compounds by the appropriate procedures. Structure of all synthesized compounds was confirmed by the various spectroscopic methods e.g. FT-IR, proton NMR and Mass spectrograms. All synthesized triazolyl-acirdines compounds were assayed in-vitro for cytotoxic activity against MCF-7 (human breast adenocarcinoma cell line) and HT-29 (human colon adenocarcinoma cell line) cells by MTT- assay. All target compounds shows increasing activity in dose dependent manner. However MPSP-9 was sensitive against MCF-7 but compound MPSP-1 was most sensitive with minimum inhibitory concentration (IC50 value) against MCF-7 and HT-29 both cell lines.