Retraction notice to "Potential of ß-elemene induced ferroptosis through Pole2-mediated p53 and PI3K/AKT signaling in lung cancer cells" [Chem. Biol. Interact. 365 (25 September 2022) 110088].

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Potential of ß-elemene induced ferroptosis through Pole2-mediated p53 and PI3K/AKT signaling in lung cancer cells.

Ferroptosis is crucial for tumor growth inhibition. Moreover, ferroptosis has been considered as a potential strategy against cancer. The present study focused on the mechanism of ferroptosis induction by ß-elemene during the lung cancer (extracted from the Chinese medicine Curcuma Wen yujin). CCK-8 assay, flow cytometry and biochemical assays including intracellular ROS, MDA, GSH, iron and 8-OHdG level were performed. DNA polymerase epsilon subunit 2 (Pole2) and the ferroptosis-related proteins were studied by utilizing western blotting. The study results showed that the ß-elemene reduced the viability of lung cancer cells via ferroptosis. Furthermore, multiple experiments confirmed that Pole2 knockdown enhanced the production of lipid ROS, MDA and iron, leading to the iron-dependent ferroptosis in lung cancer cells. Overexpression of Pole2 inhibited ß-elemene-induced ferroptosis through reduction of iron-dependent oxidative damage. Mechanically, Pole2 reduced the upregulation of p53 expression, and increased the phosphorylation levels of PI3K and AKT in ß-elemene-induced cells. Overexpression of TP53 or the inhibitor of PI3K/AKT pathway reversed the effects of Pole2. Together, ß-elemene evoked ferroptosis through the Pole2-regulated p53 or PI3K/AKT signalling, and might be an effective therapy for lung carcinogenesis.

Tinospora Cordifolia and Arabinogalactan in combination modulates benzo(a)pyrene-induced genotoxicity during lung carcinogenesis.

The present study explored the effects of combination of Tinospora cordifolia and Arabinogalactan on surface membrane dynamics and programmed cell deaths in rat model of lung cancer. The rats were divided into different groups namely normal control, benzo(a)pyrene (BP) treated, BP + Tinospora cordifolia (TC)-treated, BP + Arabinogalactan (A)-treated and BP + TC + A-treated groups. Significant changes were observed in the membrane dynamics of rats treated with BP. The carcinogen treatment demonstrated a marked decrease in membrane microviscosity. Also, excimer/monomer ratio and fluidity parameters of BP treated rats showed significant rise. On the other hand, combination of Tinospora cordifolia and Arabinogalactan improvised surface membrane dynamics. Moreover, micronuclei formation along with protein expression of bcl-2 showed significant increase in the lungs of BP treated rats. The combined treatment of Tinospora cordifolia and Arabinogalactan moderated the micronuclei formation in BP treated rats. Also, the combined treatment regulated the protein expressions of bcl-2 in BP-treated rats. As a result, marked improvement was noticed in apoptosis of BP treated cells treated with combination treatment. This study concludes that the Tinospora cordifolia and Arabinogalactan in combination improve the surface membrane dynamics and apoptosis in BP-treated rats.

Potential of Curcumin and Quercetin in Modulation of Premature Mitochondrial Senescence and Related Changes during Lung Carcinogenesis.

Ferroptosis is a classification of programmed cell death, which activates oxidative cell death in an iron and lipid peroxides-dependent manner. Targeting ferroptosis is a novel therapeutic approach for cancer therapy. Lung cancer is the leading cause of cancer related deaths all over the world. Circular RNAs (circRNAs), as a form of noncoding RNAs with a specific closed circular sequence are emerging as a new field in cancer research. However, the regulatory mechanisms of circRNAs in ferroptosis during lung cancer development are still elusive. In this work, we elucidate the potential prognostic value and the crucial role of circular RNA circFOXP1 in ferroptosis of lung cancer. We found that the expression of circFOXP1 was remarkably up-regulated in clinical lung sample tissues compared with adjacent tissues. The up-regulation of circFOXP1 was closely correlated with the poor overall survival of lung cancer patients. The knockdown of circFOXP1 suppressed the cell viability of lung cancer cells. The colony formation counts of lung cancer cells were repressed by the depletion of circFOXP1 as well. The Edu-positive lung cancer cells were attenuated by the silencing of circFOXP1. The migration and invasion of lung cancer cells were suppressed by circFOXP1 short hairpin RNA (shRNA). The expression of E-cadherin was enhanced, and vimentin expression was reduced by the knockdown of circFOXP1. Moreover, the treatment of ferroptosis activator erastin or RSL3 repressed the cell viability of lung cancer cells and the overexpression of circFOXP1 rescued the phenotype. The levels of malondialdehyde (MDA), iron, and lipid reactive oxygen species (ROS) were enhanced by the silencing of circFOXP1 in both erastin and RSL3-stimulated lung cancer cells. Mechanically, circFOXP1 increased SLC7A11 expression by directly sponging miR-520a-5p in lung cancer cells. The inhibitor of miR-520a-5p or the overexpression of SLC7A11 reversed circFOXP1 shRNA-induced ferroptosis phenotypes in lung cancer cells. Importantly, circFOXP1 contributed to tumor growth of lung cancer cells by enhancing SLC7A11 in vivo. Collectively, we concluded that circular RNA circFOXP1 is a potential diagnostic biomarker and contributes to malignant progression by repressing ferroptosis of lung cancer. Targeting circFOXP1 may be served as a promising therapeutic approach for lung cancer.

Evaluation of Potential of Long Noncoding RNA NEAT1 in Colorectal Cancer.

Long noncoding RNAs (lncRNAs) have been reported to be involved in cancer initiation and evolution, including colorectal cancer (CRC). Nuclear-enriched abundant transcript 1 (NEAT1) exerts important functions in multiple cancers; however, the specific modulatory mechanism in CRC demands in-depth exploration. The expression levels of NEAT1, microRNA-195-5p (miR-195-5p), and centrosomal protein 55 (CEP55) were examined using quantitative real-time polymerase chain reaction (qRT-PCR), and protein expression of CEP55 was detected by Western blot assay. Cell proliferation and apoptosis were measured by 3-(4,5-dimethylthiazole-2-y1)-2,5-diphenyl tetrazolium bromide (MTT) assay and flow cytometry. Transwell migration and invasion assays were applied to evaluate cell metastasis ability. Dual-luciferase reporter assay was used to analyze the correlation among NEAT1, miR-195-5p and CEP55. The expression of NEAT1 was up-regulated in CRC tissues and cells, and overall survival was lower with high expression of NEAT1. Knockdown of NEAT1 repressed cell proliferation, migration, and invasion, while inducing apoptosis in CRC cells. NEAT1 targeted miR-195-5p and inhibited the expression of miR-195-5p. Silence of NEAT1 inhibited CRC cell proliferation, migration, and invasion, and promoted apoptosis by up-regulating miR-195-5p. MiR-195-5p targeted and suppressed CEP55 expression, and CEP55 reverted the effects induced by miR-195-5p. NEAT1 regulated the expression of CEP55 through miR-195-5p. NEAT1 promotes colorectal cancer cellular processes by regulating CEP55 expression via the sponging of miR-195-5p. Therefore, NEAT1 might play a crucial role in CRC treatments.

Evaluation of biophysical as well as biochemical potential of curcumin and resveratrol during prostate cancer.

Purpose: The present study evaluated biochemical as well as biophysical mechanisms behind the synergistic effects of curcumin and resveratrol during prostate carcinogenesis.Methods: The rats were segregated into five groups that included normal control, 3,2'-dimethyl-4-aminobiphenyl (DMAB)treated, DMAB + curcumin treated, DMAB + resveratrol-treated and DMAB + curcumin + resveratrol-treated.Results: The DMAB treatment resulted in a significant increase in the levels of lipid peroxidation (LPO) in DMAB treated rats. Also, significant changes were recorded in the enzyme activities of both drug metabolising enzyme and antioxidant enzymes after DMAB treatment. Further, radiorespirometric studies showed a significant increase in the 14C-glucose turnover as well as 14C-glucose uptake in the prostate slices of DMAB treated rats. Moreover, a significant rise in cell proliferation was confirmed indirectly by enhanced uptake of 3H-thymidine in the prostate slices of DMAB treated rats. Interestingly, combined treatment of curcumin and resveratrol to DMAB treated animals resulted in a significant decrease in lipid peroxidation, 14C glucose uptakes/turnover and 3H-thymidine uptake in the DMAB treated rats. Besides this, curcumin and resveratrol in combination significantly modulated biochemical indices including drug-metabolising enzymes; antioxidant enzymes in DMBA treated rats.Conclusion: The study, therefore, concludes that the combination of curcumin and resveratrol holds strong modulatory potential against prostate carcinogenesis.

Curcumin Modulates Hepatocellular Carcinoma by Reducing UNC119 Expression.

UNCI 19 expression has been reported to be significantly higher in hepatic cancer cells (HCC). However, the clinical significance of modulating UNC119 expression in HCC is not well understood. The study described here aimed to explore the potential of curcumin in modulation of UNC119 expression in HCC by assessment with quantitative real-time PCR, western blot, and immune-histochemical analyses in HCC cell lines and tissues. The biological functions of UNC119 in the proliferation, growth, and cycle of tumor cells were analyzed both in vitro and in vivo. UNC119 expression was upregulated in HCC cell lines and tissues as indicated by comparison with normal liver cells and tissues. Cellular function assays showed that higher levels of UNC119 not only promoted proliferation but also enhanced HCC cell migration and invasion. UNC119 promoted progression of the cell cycle and significantly promoted HCC cell growth through the Wnt/ß-catenin signal pathway, and enhanced tumor migration and invasion by the TGF-ß/EMT pathway. Curcumin efficiently inhibited HCC cell proliferation by blocking the Wnt/ß-catenin pathway and inhabited migration and invasion by blocking the TGF-p/EMT signal pathway. Curcumin not only was beneficial for tumor remission but also contributed to the long-term survival of HCC-bearing mice. UNC119 was significantly upregulated and promoted cell growth in hepatic cancer cells and tissues by the Wnt/ß-catenin signal pathway and migration by TGF-ß/EMT signal pathway. Curcumin treatment inhibited cell proliferation, growth, migration, and invasion by inhibition of those pathways.

Potential of curcumin and resveratrol as biochemical and biophysical modulators during lung cancer in rats.

The present study explored chemopreventive aspects of curcumin and resveratrol in the experimental model of lung carcinogenesis in rats. The main aim was to establish efficacy of combined phytochemicals treatment over individual treatments in rat cancer model. The study was performed in terms of both biophysical and biochemical parameters. The rats were segregated into five groups, which included normal control, benzo[a]pyrene (BP) treated, BP + curcumin treated, BP + resveratrol treated, and BP + curcumin + resveratrol treated groups. The results confirmed significant changes in the biochemical indices of the BP treated rats. Further, radiorespirometric studies showed significant rise in the 14C-glucose turnover and uptakes in BP treated rats. Also, a significant increase in the cell proliferation was noticed indirectly by recording uptakes of 3H-thymidine in the lung slices of BP treated rats. On the other hand, supplementation with curcumin and resveratrol in combination to BP treated rats significantly modulated both biophysical and biochemical indices. The histopathological studies also supported the efficacy of combined treatment of phytochemicals during lung carcinogenesis. The present study concluded that the combination of curcumin and resveratrol efficiently modulated lung carcinogenesis in rats.

Potential of Ablation Therapy during Hepatocellular Carcinoma.

BACKGROUND: This study explored the potential of ablation therapy on membrane fluidity changes in diethylnitrosamine (DEN) induced hepatic cancer. METHODS: Male Wistar rats were segregated into four groups viz., normal control, DEN treated, ablation therapy treated, and DEN ablation therapy treated. We assessed the viscosities as well as fluidity parameters in isolated brush border membranes using the membrane extrinsic fluorophore pyrene. RESULTS: DEN treatment successfully induced hepatic cancer in the livers of rats and ablation therapy worked well in terms of therapy. DEN treatment resulted in a significant rise in lipid peroxidation (LPO) and significant decrease in the, reduced glutathione levels (GSH). A significant decrease was also noticed in the activities of glutathione reductase (GR), glutathione transferase (GST), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) following DEN treatment. On the other hand, ablation therapy treatment to DEN-treated rats resulted in a significant decrease in the LPO levels but caused a significant rise in the levels of GSH. Moreover, the activities of GR, GST, SOD, CAT, and GPx showed significant improvement after ablation therapy treatment. The results further demonstrated a marked decrease in membrane microviscosity following DEN treatment. On the other hand, a significant increase was noticed in both excimer/monomer ratio and fluidity parameter in DEN-treated rats. However, membrane microviscosity and the fluidity alterations were significantly restored back to near normal with ablation therapy treatment. CONCLUSIONS: The study, therefore, concluded that ablation therapy holds good therapeutic potential against DEN-induced hepatic cancer.

Modulatory Potential of Curcumin and Resveratrol on p53 Post-Translational Modifications during Gastric Cancer.

The combination approach is now a well-established treatment for cancer. The present study evaluated the potential of curcumin and resveratrol on p53 post-translational modifications during gastric cancer. We segregated rats into five groups that included normal controls, dimethylhydrazine (DMH) treated, DMH + curcumin treated, DMH + resveratrol treated, and DMH + curcumin + resveratrol treated. Morphological analyses of tumor nodules confirmed carcinogenesis in rats after 25 weeks of DMH administration. The DMH treatment significantly induced carcinogenesis, as evidenced by high tumor burden in DMH-treated rats compared with controls. Moreover, DMH treatment caused a significant increase in the protein expressions of p53 as well as p53 phosphorylation in the DMH-treated rats. In addition, a significant rise was observed in 14C glucose uptake and 3H-thymidin uptakes in DMH-treated rats. Furthermore, enzyme activities of lactate dehydrogenase and alkaline phosphatase also showed a significant rise. On the contrary, significant decline was noticed in the p53 acetylation at residue 382 of DMH-treated rats. Conversely, combined treatment with curcumin and resveratrol to DMH-treated rats resulted in significant moderation in the tumor burden. In addition, a significant rise in p53 acetylation was at residue 382 of DMH-treated rats after treatment with phytochemicals. Supplementation with phytochemicals significantly modulated other biophysical and biochemical indices to near normal levels. Therefore, we conclude that curcumin and resveratrol significantly modulated p53 post-translational modifications during gastric cancer.

Efficacy of Curcumin in Ameliorating Aluminum- Induced Neurotoxicity.

Background-The present study evaluated the efficacy of curcumin as a nutritional supplement in preventing aluminum-induced neurotoxicity in rats. Methods-The rats were segregated into four groups, which included normal controls and aluminum-treated, curcumin- treated, and aluminum- and curcumin-treated animals. Results-Eight weeks of aluminum treatment resulted in a significant increase in the levels of lipid peroxidation (LPO) and reactive oxygen species (ROS) in both cerebellum and cerebrum as compared to normal animals. In contrast, the activities of glutathione-S-transferase (GST), glutathione reductase (GR), superoxide dismutase (SOD), and reduced glutathione (GSH) levels were found to be significantly decreased following aluminum treatment. Furthermore, aluminum resulted in anxiety in rats as determined with the elevated plus maze test. In addition, an appreciable decrease was noticed in both muscular and locomotor activity of aluminum-treated animals, as determined by rotarod and actophotometer tests, respectively. However, in aluminum-treated animals that also received curcumin supplements, the already raised levels of LPO and ROS returned to near normal limits in the cerebrum. Moreover, curcumin treatment of the aluminum-treated animals also resulted in a significant improvement in the levels of GSH and enzyme activities of GST in both the cerebrum and cerebellum. Also, improvement was observed in the behavior of aluminum-treated animals upon curcumin supplementation. Conclusion-The present study suggests that curcumin may act as a neuroprotectant against aluminum-induced neurodegenerative and behavioral disorders, but further investigations are needed to understand the exact mechanism of neuroprotection.

Noncoding RNAs (ncRNA) in Hepato Cancer: A Review.

Hepatocellular carcinoma (HCC) has emerged as a prominent cancer in both developing and developed countries. Due to the increasing burden of HCC patients, massive resources are expended in their management. Furthermore, there is an urgent need to identify new molecular players that could be targeted to halt cancer development in the early phases. Noncoding RNAs (ncRNAs), which were previously thought to lack value, have the potential to play a pivotal role in the present era of personalized and translational research. Several recent studies have reported the involvement of ncRNAs in initiating, regulating, and nurturing HCC. This review provides insights regarding recently reports of noncoding RNAs and their diverse roles in initiation and development of hepatocellular carcinoma.

Potential of siRNA-albumin complex against cancer.

RNA interference is a highly specific as well as efficient technology for gene therapy application in molecular oncology. The present study was planned to develop an efficient and stable tumor selective delivery mechanism for siRNA gene therapy for the purpose of both diagnosis as well as therapy. We have used 20 Male wistar rats for the formation of colon cancer model and utilized albumin as carrier molecule for the delivery of siRNA against vascular endothelial growth factor receptor 2 (VEGF R2). The study results confirmed efficient delivery of siRNA at tumor site as confirmed by tagging of siRNA-albumin complex with 99mTC. Moreover, the expression of VEGF also showed decline after efficient delivery of siRNA at tumor site. The study concluded that albumin is an efficient molecule for the efficient delivery of siRNA at tumor sites.

Combination Approach: the Future of the War Against Cancer.

Cancer remains one of the major health problems worldwide and is responsible for one in eight deaths. The worldwide research against cancer as well as genome wide association studies was successful in indentifying the loci associated with cancer but still a substantial amount of casualty remains unexplained. The reason being the cancer cell rapidly develops resistance against the chemotherapeutic or chemopreventive agent in use. Over the last decade, the thorough understanding of molecular and biochemical mechanisms of the carcinogenesis process lead to the rationale of combining anti-cancer agents (therapeutic as well as chemopreventive) to target multiple pathways. Scientists, the world over trying various combinations of chemotherapy, radiation therapy, chemopreventive agents, nanoparticles, etc., in order to specifically as well as efficiently target cancer cells. The present review article summarizes the recent advances in the combination approach against cancer in order to enhance efficacy of treatment with minimal side effects.

Curcumin and quercetin trigger apoptosis during benzo(a)pyrene-induced lung carcinogenesis.

The aim of the present study was to assess the cumulative effects of curcumin and quercetin in inducing apoptosis during benzo(a)pyrene (BP) (100 mg/Kg body weight)-induced lung carcinogenesis in mice. BP treatment resulted in a significant increase in the protein expression of Bcl-2 whereas expression of Bax was significantly decreased. Further, BP treatment brought about a significant decrease in the activities of caspase 3, caspase 9 as well as the number of apoptotic cells. Interestingly, separate as well as combined supplementation of curcumin (60 mg/kg body weight) and quercetin (40 mg/kg body weight) to BP-treated animals resulted in a significant decrease in the protein expression of Bcl-2 but caused a significant increase in the protein expression of Bax along with a noticeable improvement in the number of apoptotic cells. Also, supplementation with curcumin and quercetin separately to BP-treated mice brought a significant improvement in the enzyme activities of caspase 9 as well as caspase 3 but the improvement was more pronounced following combined treatment. Therefore, curcumin and quercetin, if given in combination shall exhibit enhanced chemopreventive potential against development of lung carcinogenesis by stimulating the apoptotic machinery.

Radiolabeling in Biology.

Chemistry is the science of chemical reactions, the study of chemical properties, composition, and structure of a molecule. When the molecule under observation is of a biological origin (proteins, carbohydrates, lipids, or nucleic acids), the study of its chemical properties, reactions, and structure is known as biochemistry. Similarly, if the molecule or a biochemical under observation is radioactive, the science becomes radiochemistry or radio biochemistry. So, chemistry is the science which fuses these two diverse fields of applied sciences. Fusion of these two sciences on chemistry platform has enabled the development of various new radioactive formulations which are called as radiopharmaceuticals and are being used the world over for clinical as well as experimental purposes. For the successful development of radiopharmaceuticals, we require in-depth understanding of both biochemistry as well as radiochemistry. So, the present review article summarizes basic relevant details and experimental advances in both these sciences with regard to development of radiopharmaceuticals.

SiRNA gene therapy using albumin as a carrier.

RNA interference or post-transcriptional gene silencing is one of the latest, innovative, highly specific, and efficient technologies for gene therapy application in molecular oncology. It is already a well-established research tool for analyses of molecular mechanisms for various diseases including cancer as it efficiently silences the expression of genes of interest. However, for its proper therapeutic use, an efficient tumor-specific in-vivo delivery mechanism is essential. Many scientific groups and companies are involved in the development of efficient in-vivo delivery mechanisms for small interfering RNA, but are still struggling. The present article suggests utilization of albumin as a delivery module for small interfering RNA as it is an endogenous natural nanoparticle known for its binding properties to various endogenous metabolites, drugs, and metal ions.

Current view of zinc as a hepatoprotective agent in conditions of chlorpyrifos induced toxicity.

Human population bears the brunt of deadly hepatotoxic, neurodegenerative, behavioural and various other developmental disorders due to pesticide toxicity through environmental or occupational exposures. The application of pesticides to control pests in land and water has posed potential health hazards to live stock and wildlife including fishes, mammals, birds and humans. Therefore, various scientific approaches are being considered to tackle the problem of pesticide poisoning especially in developing economies. The role of essential trace elements as the promising and efficient preventive prophylactic agents without any toxicity and side effects in attenuating the adverse effects caused by pesticides, have been reported by various scientists, the world over. In this perspective, zinc, a key constituent of more than 300 mammalian enzymes and many transcription factors has proved its protective potential in various models of animal toxicity. The hepato-protective potential of zinc has been proved during various toxic states including pesticide toxicity. However, zinc warrants further examination with regard to documentation of specific molecular pathways to establish the exact mechanisms for zinc-mediated protection during pesticide toxicity.

Epigenetic targets of polyphenols in cancer.

Interest in dietary polyphenols has recently increased greatly owing to their antioxidant capacity and their possible beneficial implications in various pathological states, including cancer. Polyphenols are a group of chemicals found in many fruits, vegetables, and plants and have the ability to remove free radicals from the body. In the last 2 decades, the numbers of reports on the potential health benefits of polyphenols have increased. This review provides the available scientific data that justify importance of polyphenols in correlation with epigenetics to fight against carcinogenesis. Epigenetics involves genetic control by mechanisms other than DNA sequence. These epigenetic mechanisms have ability to switch on or off various important genes influencing the process of cancer. Furthermore, due to the reversible nature of these epigenetic mechanisms, they are influenced by a variety of dietary polyphenols. This review focuses on the dietary polyphenols that significantly affect these epigenetic mechanisms to mitigate carcinogenesis.