Calebin A targets the HIF-1α/NF-κB pathway to suppress colorectal cancer cell migration

Background: Hypoxia-inducible factor-1α (HIF-1α) is one of the major tumor-associated transcription factors modulating numerous tumor properties such as tumor cell metabolism, survival, proliferation, angiogenesis, and metastasis. Calebin A (CA), a compound derived from turmeric, is known for its anti-cancer activity through modulation of the NF-κB pathway. However, its impact on HIF-1α in colorectal cancer (CRC) cell migration is unknown.Methods: Human CRC cells (HCT-116) in 3D alginate and monolayer multicellular TME (fibroblasts/T lymphocytes) were subjected to CA or the HIF-1α inhibitor to explore the efficacy of CA on TME-induced inflammation, migration, and tumor malignancy.Results: CA significantly inhibited TME-promoted proliferation and migration of HCT-116 cells, similar to the HIF-1α inhibitor. Colony formation, toluidine blue staining, and immunolabeling showed that CA inhibited the migration of HCT-116 cells partly by inhibiting HIF-1α, which is critical for CRC cell viability, and these observations were confirmed by electron microscopy. In addition, Western blot analysis confirmed that CA inhibited TME-initiated expression of HIF-1α and biomarkers of metastatic factors (such as NF-κB, β1-integrin, and VEGF), and promoted apoptosis (caspase-3), in a manner comparable to the HIF-1α inhibitor. Finally, TME induced a purposeful pairing between HIF-1α and NF-κB, suggesting that the synergistic interplay between the two tumor-associated transcription factors is essential for CRC cell malignancy and migration and that CA silences these factors in tandem.Conclusion: These results shed light on a novel regulatory modulation of CA signaling in CRC cell migration, partially via HIF-1α/NF-κB with potentially relevant implications for cancer therapy

Reiterating the Emergence of Noncoding RNAs as Regulators of the Critical Hallmarks of Gall Bladder Cancer

Gall bladder cancer (GBC) is a rare and one of the most aggressive types of malignancies, often associated with a poor prognosis and survival. It is a highly metastatic cancer and is often not diagnosed at the initial stages, which contributes to a poor survival rate of patients. The poor diagnosis and chemoresistance associated with the disease limit the scope of the currently available surgical and nonsurgical treatment modalities. Thus, there is a need to explore novel therapeutic targets and biomarkers that will help relieve the severity of the disease and lead to advanced therapeutic strategies. Accumulating evidence has correlated the atypical expression of various noncoding RNAs (ncRNAs), including circular RNAs (circRNAs), long noncoding RNAs (lncRNAs), microRNAs (miRNAs), and small nucleolar RNAs (snoRNA) with the increased cell proliferation, epithelial–mesenchymal transition (EMT), invasion, migration, metastasis, chemoresistance, and decreased apoptosis in GBC. Numerous reports have indicated that the dysregulated expression of ncRNAs is associated with poor prognosis and lower disease-free and overall survival in GBC patients. These reports suggest that ncRNAs might be considered novel diagnostic and prognostic markers for the management of GBC. The present review recapitulates the association of various ncRNAs in the initiation and progression of GBC and the development of novel therapeutic strategies by exploring their functional and regulatory role

Potential of baicalein in the prevention and treatment of cancer: A scientometric analyses based review

10.1016/j.jff.2021.104660Journal of Functional Foods8610466

Unraveling the Potential Role of NEDD4-like E3 Ligases in Cancer

Cancer is a deadly disease worldwide, with an anticipated 19.3 million new cases and 10.0 million deaths occurring in 2020 according to GLOBOCAN 2020. It is well established that carcinogenesis and cancer development are strongly linked to genetic changes and post-translational modifications (PTMs). An important PTM process, ubiquitination, regulates every aspect of cellular activity, and the crucial enzymes in the ubiquitination process are E3 ubiquitin ligases (E3s) that affect substrate specificity and must therefore be carefully regulated. A surfeit of studies suggests that, among the E3 ubiquitin ligases, neuronal precursor cell-expressed developmentally downregulated 4 (NEDD4)/NEDD4-like E3 ligases show key functions in cellular processes by controlling subsequent protein degradation and substrate ubiquitination. In addition, it was demonstrated that NEDD4 mainly acts as an oncogene in various cancers, but also plays a tumor-suppressive role in some cancers. In this review, to comprehend the proper function of NEDD4 in cancer development, we summarize its function, both its tumor-suppressive and oncogenic role, in multiple types of malignancies. Moreover, we briefly explain the role of NEDD4 in carcinogenesis and progression, including cell survival, cell proliferation, autophagy, cell migration, invasion, metastasis, epithelial-mesenchymal transition (EMT), chemoresistance, and multiple signaling pathways. In addition, we briefly explain the significance of NEDD4 as a possible target for cancer treatment. Therefore, we conclude that targeting NEDD4 as a therapeutic method for treating human tumors could be a practical possibility

Sorcin a Potential Molecular Target for Cancer Therapy

Sorcin (Soluble resistance related calcium binding protein) is a small soluble penta EF family (PEF) of calcium (Ca2+) binding protein (22,000 Da). It has been reported to play crucial roles in the regulation of calcium homeostasis, apoptosis, vesicle trafficking, cancer development, and multidrug resistance (MDR). Overexpression of sorcin has been reported to be associated with different cancers such as breast cancer, colorectal cancer, gastric cancer, leukemia, lung cancer, nasopharyngeal cancer, ovarian cancer, etc. Essentially, expression of sorcin has been found to be elevated in cancer cells as compared to normal cells, indicating that it has prominent role in cancer. Moreover, sorcin was found to be the regulator of various proteins that has an association with carcinogenesis including NF-κB, STAT3, Akt, ERK1/2, VEGF, MMPs, caspases, etc. Sorcin was also found to regulate apoptosis, as silencing of the same resulted in increased levels of proapoptotic genes and induced mitochondrial apoptotic pathway in cancer. Interestingly, mutations in the sorcin gene have been closely linked with poor overall survival in bladder cancer, brain lower-grade glioma, glioblastoma, glioblastoma multiforme, kidney renal clear cell carcinoma, and stomach adenocarcinoma. Additionally, overexpression of sorcin was also found to induce MDR against different chemotherapeutic drugs. All these findings mark the importance of sorcin in cancer development and MDR. Therefore, there is urgent need to explore the functional mechanism of sorcin and to analyze whether silencing of sorcin would able to chemosensitize MDR cells. The current review summarizes the structure, expression, and functions of sorcin and its importance in the regulation of various malignancies and MDR

From Simple Mouth Cavities to Complex Oral Mucosal Disorders - Curcuminoids as a Promising Therapeutic Approach

10.1021/acsptsci.1c00017ACS Pharmacology & Translational Scienc

Potential of Zerumbone as an Anti-Cancer Agent

Cancer is still a major risk factor to public health globally, causing approximately 9.8 million deaths worldwide in 2018. Despite advances in conventional treatment modalities for cancer treatment, there are still few effective therapies available due to the lack of selectivity, adverse side effects, non-specific toxicities, and tumour recurrence. Therefore, there is an immediate need for essential alternative therapeutics, which can prove to be beneficial and safe against cancer. Various phytochemicals from natural sources have been found to exhibit beneficial medicinal properties against various human diseases. Zerumbone is one such compound isolated from Zingiber zerumbet Smith that possesses diverse pharmacological properties including those of antioxidant, antibacterial, antipyretic, anti-inflammatory, immunomodulatory, as well as anti-neoplastic. Zerumbone has shown its anti-cancer effects by causing significant suppression of proliferation, survival, angiogenesis, invasion, and metastasis through the molecular modulation of different pathways such as NF-κB, Akt, and IL-6/JAK2/STAT3 (interleukin-6/janus kinase-2/signal transducer and activator of transcription 3) and their downstream target proteins. The current review briefly summarizes the modes of action and therapeutic potential of zerumbone against various cancers

Oroxylin A: A Promising Flavonoid for Prevention and Treatment of Chronic Diseases

There have been magnificent advancements in the understanding of molecular mechanisms of chronic diseases over the past several years, but these diseases continue to be a considerable cause of death worldwide. Most of the approved medications available for the prevention and treatment of these diseases target only a single gene/protein/pathway and are known to cause severe side effects and are less effective than they are anticipated. Consequently, the development of finer therapeutics that outshine the existing ones is far-reaching. Natural compounds have enormous applications in curbing several disastrous and fatal diseases. Oroxylin A (OA) is a flavonoid obtained from the plants Oroxylum indicum, Scutellaria baicalensis, and S. lateriflora, which have distinctive pharmacological properties. OA modulates the important signaling pathways, including NF-κB, MAPK, ERK1/2, Wnt/β-catenin, PTEN/PI3K/Akt, and signaling molecules, such as TNF-α, TGF-β, MMPs, VEGF, interleukins, Bcl-2, caspases, HIF-1α, EMT proteins, Nrf-2, etc., which play a pivotal role in the molecular mechanism of chronic diseases. Overwhelming pieces of evidence expound on the anti-inflammatory, anti-bacterial, anti-viral, and anti-cancer potentials of this flavonoid, which makes it an engrossing compound for research. Numerous preclinical and clinical studies also displayed the promising potential of OA against cancer, cardiovascular diseases, inflammation, neurological disorders, rheumatoid arthritis, osteoarthritis, etc. Therefore, the current review focuses on delineating the role of OA in combating different chronic diseases and highlighting the intrinsic molecular mechanisms of its action

FBXW7 in Cancer: What Has Been Unraveled Thus Far?

The FBXW7 (F-box with 7 tandem WD40) protein encoded by the gene FBXW7 is one of the crucial components of ubiquitin ligase called Skp1-Cullin1-F-box (SCF) complex that aids in the degradation of many oncoproteins via the ubiquitin-proteasome system (UPS) thus regulating cellular growth. FBXW7 is considered as a potent tumor suppressor as most of its target substrates can function as potential growth promoters, including c-Myc, Notch, cyclin E, c-JUN, and KLF5. Its regulators include p53, C/EBP-δ, Numb, microRNAs, Pin 1, Hes-5, BMI1, Ebp2. Mounting evidence has indicated the involvement of aberrant expression of FBXW7 for tumorigenesis. Moreover, numerous studies have also shown its role in cancer cell chemosensitization, thereby demonstrating the importance of FBXW7 in the development of curative cancer therapy. This comprehensive review emphasizes on the targets, functions, regulators and expression of FBXW7 in different cancers and its involvement in sensitizing cancer cells to chemotherapeutic drugs