Bladder cancer is a disease that negatively affects patients’ quality of life, but treatment options have remained unchanged for a long time. Although promising results have been achieved with current bladder cancer treatments, cancer recurrence, progression, and therapy resistance are the most severe problems preventing the efficiency of bladder cancer treatments. Autophagy refers to an evolutionarily conserved catabolic process in which proteins, damaged organelles, and cytoplasmic components are degraded by lysosomal enzymes. Autophagy regulates the therapeutic response to the chemotherapy drugs, thus determining the effect of therapy on cancer cells. Autophagy is a stress-induced cell survival mechanism and its excessive stimulation can cause resistance of tumor cells to therapeutic agents. Depending on the conditions, an increase in autophagy may cause treatment resistance or autophagic cell death, and it is related to important anti-cancer mechanisms, such as apoptosis. Therefore, understanding the roles of autophagy under different conditions is important for designing effective anti-cancer agents. The dual role of autophagy in cancer has attracted considerable attention in respect of bladder cancer treatment. In this review, we summarize the basic characteristics of autophagy, including its mechanisms, regulation, and functions, and we present examples from current studies concerning the dual role of autophagy in bladder cancer progression and therapy. Impact statement Autophagy acts as an intracellular recycling system. Infection and mitochondrial damage, maintaining cellular homeostasis, orchestrating nutrient stress, hypoxia, and oxidative stress are some of the physiological roles associated with autophagy. Autophagy has also context-dependent roles in cancer. Autophagy has a significant impact on tumor initiation and promotion, with both tumor-suppressive and tumor-promoting roles. Unfortunately, conventional systemic chemotherapy for cancer therapy has been reported to have primary limitations such as chemo-resistance of targeted cells. The cytoprotective role of autophagy has been postulated as one of the causes of this resistance. Hence, combination therapy using autophagy inhibitors has recently started to emerge as a noteworthy strategy in the treatment of cancer. Therefore, targeting the autophagy pathways may be a potential therapeutic strategy for addressing cancer progression or therapy resistance in the near future. This review will provide a novel insight to understanding the paradoxical roles of autophagy in tumor suppression and tumor promotion.

Cisplatin-based chemotherapy is the standard regimen for bladder cancer patients, but its effectiveness is limited by high toxicity and the development of drug resistance. It has been reported in many studies that Cucurbitacin B has anti-carcinogenic effects by stimulating apoptosis and autophagy. Here we explored the potential role of cucurbitacin B on MB49 bladder syngeneic mouse tumor model. Single and combined doses of cucurbitacin B and cisplatin were applied to MB49 cell line and the cell viability was determined by Water‐Soluble Tetrazolium Salt‐1 (WST) method. After developing the tumor model, mice were randomly divided into four groups and then cucurbitacin B and cisplatin applied in the specified doses and time. The expression levels of apoptosis (Bcl-2, Bax, Caspase-3, cleaved Caspase-3) and autophagy proteins (Beclin-1 and LC3I, LC3II) were detected by Western Blot. Phospho-protein array analysis was performed to determine the relative levels of phosphorylation of proteins which are associated with the PI3K-Akt signaling pathway. Tumor tissues were analyzed by hematoxylin-eosin staining. In the present study, the results showed that cucurbitacin B inhibited the expression of Bcl-2 and increased the expression of Bax and cleaved Caspase 3. LC3II is markedly up-regulated in cucurbitacin B-treated cells. Cucurbitacin B reduced the phosphorylation of p27, PRAS40, and Raf-1 proteins. CuB + Cis combination synergistically decreased phosphorylation of AKT, ERK1/ERK2, mTOR, BAD levels and increased the level of AMPKα. PI3K/AKT/ mTOR pathway might be one of the targets of cucurbitacin B in MB49 bladder cancer mouse model. CuB + Cis combination reduced the tumor growth. Cucurbitacin B has no toxic effects on lung, liver, kidney, heart, and bladder. Indeed, cucurbitacin B can inhibit the tumor proliferation; induce caspase-dependent/-independent apoptosis and autophagy. Our study provided a novel perspective to research the effects of cucurbitacin B on the apoptotic and autophagic pathways in bladder cancer and a new target class for drug development. Impact statement Alternative agents that will increase the effectiveness of cisplatin, which are widely used in the advanced stage and metastatic bladder cancer, are being investigated. In previous studies, Cucurbitacin B (CuB), which is a natural compound from the Cucurbitaceae family has been shown to inhibit the proliferation of tumor cells and create synergistic effects with cisplatin. In this study, we investigated the synergistic effect of CuB with cisplatin for the first time in bladder cancer in vitro and in vivo models. Our findings showed that CuB treatment with cisplatin reduced cell proliferation, and reduced tumor development through activating apoptosis and autophagy via PI3K/AKT/mTOR signaling pathway. Our results showed that CuB may be a new agent that can support conventional treatment in bladder cancer. Our study is important in terms of enlightening new pathways and developing new treatment methods in the treatment of bladder cancer.

Parkinson Hastalığı, Alzheimer hastalığından sonra ikinci en sık görülen nörodejeneratif bir hastalıktır. Parkinson hastalığının temel patolojik bulguları; orta beyindeki substantia nigra pars compacta ve striatumdaki dopaminerjik nöronların ilerleyici kaybı ve Lewy cisimcikleri olarak adlandırılan inklüzyonların nöronlarda birikimidir. Birçok araştırmacı, Parkinson hastalığının nadiren ailesel olduğunu, özellikle sporadik faktörlerin (çevresel ve genetik) bu hastalığın başlamasına ve ilerlemesine neden olduğunu göstermiştir. Bugüne kadar Parkinson hastalığına bağlı 26 gen lokusu tanımlanmıştır. Bu çalışmanın amacı, Parkinson hastalığı ile ilişkili genler üzerine literatüre katkı sağlamaktır.

Methoxy group enriched eight coumarin-chalcone hybrid derivatives were synthesized. Antimicrobial/ antiproliferative activities were tested against eight human pathogenic microorganisms and four cancer cell lines (AGS, HepG2, MCF-7 and PC-3), respectively. Antimicrobial results showed that most of the compounds were almost more active than used standard antibiotics. Cytotoxicity results showed that 2,3,4-trimethoxyphenyl and thiophene containing structures have promising antiproliferative effects against AGS gastric cell lines with ~5 μg/ml IC 50 values. At the same time, 2,4-dimethoxyphenyl bearing derivative exhibited the lowest IC 50 values against HepG2 (~10 μg/ml) and PC-3 (~5 μg/ml) cell lines. Particularly, the cell viabilities of MCF-7 cell lines were remarkably inhibited by all the compounds with lower IC 50 values. Therefore, molecular docking studies between hybrid ligands and quinone reductase-2 enzyme (regulates in MCF-7 cancer cells) were performed. The results demonstrated that all the derivatives can smoothly interact with interested enzyme in agreement with the experimental results. Finally, ADME parameters were studied to reveal drug-likeness potentials of the coumarinchalcone hybrids.

Aim: Previous studies have reported that Phlomis russeliana shows cytotoxic effects against several cancer cell lines; however, its anti cancer activity on HCT-116 cancer cells has not yet been investigated. Therefore, the present study is designed to explore anti-cancer properties of Phlomis russeliana against HCT-116 human colon cancer cell line and HUVEC normal cell line. Material and Methods: HCT-116 cells and HUVECs treated with different concentrations of Phlomis russeliana (2, 4, 6, 8 and 10 mg/ml) and cell viability evaluated by the MTT assay. Anti-migratory and anti-colonigenic effects of Phlomis russeliana were assessed with wound healing and colony formation assays respectively. Quantitative determination of total antioxidant status (TAS), total oxidant status (TOS) and caspase-3 activation were performed with colorimetric Elisa kits. Results: Phlomis russeliana significantly decreased cell viability of HCT-116 cells in a concentration dependent and showed weaker toxicity against normal HUVECs. Pholomis russeliana significantly inhibited migration and colony formation potential of HCT-116 cells. A significant increase in caspase-3 activation was observed after treatment with Phlomis russeliana. Phlomis russeliana did not significantly affect the TAS and TOS level in HCT-116 cells. Conclusion: These results revealed that Phlomis russeliana showed anti-cancer activity in human colon cancer cells, through the suppression of colony formation, inhibition of migration and induction of caspase-3 activation. Phlomis russeliana, could be a promising source for the development of new anti-cancer agents against cancer.