Role of TRP channels in carcinogenesis and metastasis: Pathophysiology and regulation by non-coding RNAs.

In 2021, David Julius and Ardem Patapoutian received Nobel Prize in Physiology or Medicine for their ground-breaking discoveries in the functional characterization of receptors for temperature and touch. Transient receptor potential (TRP) channels have captivated tremendous appreciation as promising drug targets over the past few years because of central involvement in different cancers. Based on the insights gleaned from decades of high-quality research, basic and clinical scientists have unveiled how Transient receptor potential channels regulated cancer onset and progression. Pioneering studies have sparked renewed interest and researchers have started to scratch the surface of mechanistic role of these channels in wide variety of cancers. In this review we have attempted to provide a summary of most recent updates and advancements made in the biology of these channels in context of cancers. We have partitioned this review into different subsections on the basis of emerging evidence about characteristically distinct role of TRPV (TRPV1, TRPV5), TRPM (TRPM3, TRPM7) and TRPC in cancers. Regulation of TRP channels by non-coding RNAs is also a very exciting area of research which will be helpful in developing a sharper understanding of the multi-step aspects of cancers.

Bufalin-Mediated Regulation of Cell Signaling Pathways in Different Cancers: Spotlight on JAK/STAT, Wnt/ß-Catenin, mTOR, TRAIL/TRAIL-R, and Non-Coding RNAs.

The renaissance of research into natural products has unequivocally and paradigmatically shifted our knowledge about the significant role of natural products in cancer chemoprevention. Bufalin is a pharmacologically active molecule isolated from the skin of the toad Bufo gargarizans or Bufo melanostictus. Bufalin has characteristically unique properties to regulate multiple molecular targets and can be used to harness multi-targeted therapeutic regimes against different cancers. There is burgeoning evidence related to functional roles of signaling cascades in carcinogenesis and metastasis. Bufalin has been reported to regulate pleiotropically a myriad of signal transduction cascades in various cancers. Importantly, bufalin mechanistically regulated JAK/STAT, Wnt/ß-Catenin, mTOR, TRAIL/TRAIL-R, EGFR, and c-MET pathways. Furthermore, bufalin-mediated modulation of non-coding RNAs in different cancers has also started to gain tremendous momentum. Similarly, bufalin-mediated targeting of tumor microenvironments and tumor macrophages is an area of exciting research and we have only started to scratch the surface of the complicated nature of molecular oncology. Cell culture studies and animal models provide proof-of-concept for the impetus role of bufalin in the inhibition of carcinogenesis and metastasis. Bufalin-related clinical studies are insufficient and interdisciplinary researchers require detailed analysis of the existing knowledge gaps.

Suppressive effects of bioactive herbal polysaccharides against different cancers: From mechanisms to translational advancements.

BACKGROUND: Fueled by rapidly evolving comprehension of multifaceted nature of cancers, recently emerging preclinical and clinical data have supported researchers in the resolution of knowledge gaps to deepen the understanding of the molecular mechanisms. The extra-ordinary and bewildering chemical diversity encompassed by biologically active natural products continues to be of relevance to drug discovery. Accumulating evidence has spurred a remarkable evolution of concepts related to pharmacological target of oncogenic signaling pathways by polysaccharides in different cancers. PURPOSE: The objective of the current review is to provide new insights into study progress on anticancer effects of bioactive herbal polysaccharides. METHODS: PubMed, Scopus, Web of Science, Embase, and other databases were searched for articles related to anticancer effects of polysaccharides. Searches were conducted to locate relevant publications published up to October 2022. RESULTS: Polysaccharides have been reported to pleiotropically modulate TGF/SMAD, BMP/SMAD, TLR4, mTOR, CXCR4 and VEGF/VEGFR cascades. We have also summarized how different polysaccharides regulated apoptosis and non-coding RNAs. Additionally, this mini-review describes increasingly sophisticated understanding related to polysaccharides mediated tumor suppressive and anti-metastatic effects in tumor-bearing mice. We have also provided an overview of the clinical trials related to chemopreventive role of polysaccharides. CONCLUSION: Genomic and proteomic findings from these studies will facilitate 'next-generation' clinical initiatives in the prevention/inhibition of cancer.

Multifunctional Roles of Betulinic Acid in Cancer Chemoprevention: Spotlight on JAK/STAT, VEGF, EGF/EGFR, TRAIL/TRAIL-R, AKT/mTOR and Non-Coding RNAs in the Inhibition of Carcinogenesis and Metastasis.

The pursual of novel anticancer molecules from natural sources has gained worthwhile appreciation, and a significant fraction of conceptual knowledge has revolutionized our understanding about heterogeneous nature of cancer. Betulinic acid has fascinated interdisciplinary researchers due to its tremendous pharmacological properties. Ground-breaking discoveries have unraveled previously unprecedented empirical proof-of-concept about momentous chemopreventive role of betulinic acid against carcinogenesis and metastasis. Deregulation of cell signaling pathways has been reported to play a linchpin role in cancer progression and colonization of metastatically competent cancer cells to the distant organs for the development of secondary tumors. Importantly, betulinic acid has demonstrated unique properties to mechanistically modulate oncogenic transduction cascades. In this mini-review, we have attempted to provide a sophisticated compendium of regulatory role of betulinic acid in cancer chemoprevention. We have partitioned this multi-component review into different sections in which we summarized landmark research-works which highlighted betulinic acid mediated regulation of JAK/STAT, VEGF, EGF/EGFR, TRAIL/TRAIL-R, AKT/mTOR and ubiquitination pathways in the inhibition of cancer. In parallel, betulinic acid mediated regulation of signaling cascades and non-coding RNAs will be critically analyzed in cell culture and animal model studies. Better comprehension of the pharmaceutical features of betulinic acid and mapping of the existing knowledge gaps will be valuable in the translatability of preclinical studies into rationally designed clinical trials.