The protein restriction mimetic Resveratrol is an autophagy inducer stronger than amino acid starvation in ovarian cancer cells

2017 ◽  
Vol 56 (12) ◽  
pp. 2681-2691 ◽  
Author(s):  
Alessandra Ferraresi ◽  
Rossella Titone ◽  
Carlo Follo ◽  
Andrea Castiglioni ◽  
Giovanna Chiorino ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Amino Acid ◽  
Cancer Cells ◽  
Amino Acid Starvation ◽  
Protein Restriction ◽  
Ovarian Cancer Cells

scholarly journals The anti-ovarian carcinoma activity of L-amino Acid Oxidase from Crotalus adamanteus venom in vivo and in vitro

2021 ◽  
Author(s):  
Li Bo ◽  
Yan Xiong ◽  
Qiyi He ◽  
Xiaodong Yu ◽  
Bo Li ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Amino Acid ◽  
Cancer Cells ◽  
Morphological Changes ◽  
Complex Mixture ◽  
Ovarian Cancer Cells ◽  
Acid Oxidase ◽  
Amino Acid Oxidase ◽  
Apoptosis Pathway

Abstract The anti-tumor potential of animal toxins has fully attracted the attention of researchers. Snake venoms is a complex mixture of different components and has revealed high toxicity on normal and tumoral tissues or cells. The snake venom L-Amino-acid oxidase (svLAAO) has grown up to be a critical research target in molecular biology sciences and medicine sciences since widespread presence and various biological roles, including antitumor application. We found that Crotalus adamanteus (C. adamanteus) venom LAAO significantly decreased the viability of ovarian cancer cells and caused morphological changes preceded cell death. Cell experiments confirmed that C. adamanteus venom LAAO caused alterations of intrinsic or extrinsic apoptosis pathway-related genes in ovarian cancer cells. Animal experiments and histological analysis also proved that C. adamanteus venom LAAO could effectively inhibit the damage of ovarian cancer to tissues. The major apoptosis induction of C. adamanteus venom LAAO on ovarian cancer cells can be blocked by catalase, suggesting that the cytotoxicity of C. adamanteus venom LAAO on ovarian cancer cells was mainly mediated by H2O2. Our preliminary results revealed that C. adamanteus venom LAAO may induce apoptosis of ovarian cancer cells through the death receptor pathway and mitochondrial pathway. It is inferred that C. adamanteus venom LAAO will be some advantages in New Drug Research and Development of antitumor drugs in the future. Nevertheless, extra studies on the pharmacological actions and molecular mechanism of svLAAO in anti-cancer are necessary in order to better promote its application.

scholarly journals Lipoamino Acid-Modified GnRH Analogs with Receptor-Mediated Antiproliferative Activity in Prostate and Ovarian Cancer Cells

2021 ◽  
Author(s):  
Pegah Varamini ◽  
Kimmi Dhiman ◽  
Sepideh Khazeni ◽  
Frieda Mansfeld ◽  
Istvan Toth
Keyword(s):  
Ovarian Cancer ◽  
Amino Acid ◽  
Cancer Cells ◽  
Amino Acid Substitution ◽  
Anticancer Agents ◽  
Antiproliferative Activity ◽  
Gnrh Receptor ◽  
Ovarian Cancer Cells ◽  
Gnrh Analogs ◽  
Reproductive Cancers

Abstract Gonadotropin-releasing hormone (GnRH) analogs (e.g., triptorelin) are developed to treat hormone-dependent reproductive cancers. However, these analogs lack any significant direct antitumor activity to make them suitable for hormone-refractory reproductive cancers. In this study, we modified GnRH peptide and triptorelin to improve their stability, pharmacokinetic properties, and potency and subsequently broaden their clinical applications in cancer. We investigated biological properties of lipid-modified GnRH analogs, with/without D-amino acid substitution at position 6 to yield GnRH- and triptorelin-based derivatives, respectively, in prostate and ovarian cancer cells. We showed that the improved stability due to lipid-modification and D-amino acid substitution played a pivotal role in enhancing GnRH receptor-mediated direct antiproliferative activity (up to 4.5-fold higher than triptorelin) and gonadotropin-releasing potency. Furthermore, sex steroids played significant but contrasting roles in regulating the direct antiproliferative activity of the lipopeptides in cancer cells. The superior activity of these GnRH analogs over triptorelin renders promises for developing new GnRH receptor ligands to treat hormone-dependent and -refractory cancers, as well as emerging new targeting moieties for the delivery of anticancer agents in GnRH receptor-overexpressing cancers.

scholarly journals Amino Acid Deprivation-Induced Autophagy Requires Upregulation of DIRAS3 through Reduction of E2F1 and E2F4 Transcriptional Repression

Cancers ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 603 ◽  
Author(s):  
Margie N. Sutton ◽  
Gilbert Y. Huang ◽  
Jinhua Zhou ◽  
Weiqun Mao ◽  
Robert Langley ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Amino Acid ◽  
Cancer Cells ◽  
Transcriptional Repression ◽  
Xenograft Model ◽  
Suppressor Gene ◽  
Nutrient Sensing ◽  
Ovarian Cancer Cells ◽  
Drug Resistant ◽  
Amino Acid Deprivation

Failure to cure ovarian cancer relates to the persistence of dormant, drug-resistant cancer cells following surgery and chemotherapy. “Second look” surgery can detect small, poorly vascularized nodules of persistent ovarian cancer in ~50% of patients, where >80% are undergoing autophagy and express DIRAS3. Autophagy is one mechanism by which dormant cancer cells survive in nutrient poor environments. DIRAS3 is a tumor suppressor gene downregulated in >60% of primary ovarian cancers by genetic, epigenetic, transcriptional and post-transcriptional mechanisms, that upon re-expression can induce autophagy and dormancy in a xenograft model of ovarian cancer. We examined the expression of DIRAS3 and autophagy in ovarian cancer cells following nutrient deprivation and the mechanism by which they are upregulated. We have found that DIRAS3 mediates autophagy induced by amino acid starvation, where nutrient sensing by mTOR plays a central role. Withdrawal of amino acids downregulates mTOR, decreases binding of E2F1/4 to the DIRAS3 promoter, upregulates DIRAS3 and induces autophagy. By contrast, acute amino acid deprivation did not affect epigenetic regulation of DIRAS3 or expression of miRNAs that regulate DIRAS3. Under nutrient poor conditions DIRAS3 can be transcriptionally upregulated, inducing autophagy that could sustain dormant ovarian cancer cells.

Cytotoxic effects of disulfiram and synergism with cisplatin on ovarian cancer cells in vitro

2018 ◽  
Author(s):  
F Guo ◽  
Z Yang ◽  
J Xu ◽  
J Sehouli ◽  
AE Albers ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Ovarian Cancer Cells ◽  
Cytotoxic Effects
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