2-3-4-tri-o-acetylarabinopyranosyl-isothiocyanate and Neoplasms

Allyl isothiocyanates (AITC) have gained recognition in recent years as effective chemotherapeutic and epigenetic modulators. The chemopreventive properties and toxicological perspectives of AITCs from the last few decades were taken into account by a number of investigations. Their active therapeutic relevance was hindered by a number of factors, including instability under typical physiological conditions and low bioavailability due to low aqueous solubility. In this review, we highlighted the chemopreventive attributes of AITC in relation to its molecular mechanisms and metabolic fate for cancer. Moreover, we emphasized on investigational anticancer activities and various strategies for delivery of AITC in different types of cancer. Considering cellular interactions, we shed light on the toxicological properties of AITCs to address further issues regarding their assessment in therapeutic development. This review identifies knowledge gaps with various contemporary approaches involving most recent studies and may pave the way for a better understanding for the development of novel AITC therapeutics.

Topics: Humans; Isothiocyanates; Neoplasms

Patients suffering from cancer induced bone pain (CIBP) have a poor quality of life that is exacerbated by the lack of effective therapeutic drugs. Monkshood is a flowering plant that has been used in traditional Chinese medicine where it has been used to relieve cold pain. Aconitine is the active component of monkshood, but the molecular mechanism for how this compound reduces pain is unclear.. In this study, we employed molecular and behavioral experiments to explore the analgesic effect of aconitine. We observed aconitine alleviated cold hyperalgesia and AITC (allyl-isothiocyanate, TRPA1 agonist) induced pain. Interestingly, we found aconitine directly inhibits TRPA1 activity in calcium imaging studies. More importantly, we found aconitine alleviated cold and mechanical allodynia in CIBP mice. Both the activity and expression of TRPA1 in L4 and L5 DRG (Dorsal Root Ganglion) neurons were reduced with the treatment of aconitine in the CIBP model. Moreover, we observed aconiti radix (AR) and aconiti kusnezoffii radix (AKR), both components of monkshood that contain aconitine, alleviated cold hyperalgesia and AITC induced pain. Furthermore, both AR and AKR alleviated CIBP induced cold allodynia and mechanical allodynia.. Taken together, aconitine alleviates both cold and mechanical allodynia in cancer induced bone pain via the regulation of TRPA1. This research on the analgesic effect of aconitine in cancer induced bone pain highlights a component of a traditional Chinese medicine may have clinical applications for pain.

Topics: Aconitine; Analgesics; Animals; Cancer Pain; Hyperalgesia; Mice; Neoplasms; Pain; Quality of Life; TRPA1 Cation Channel

Angiogenesis, invasion, and metastasis are the main events of cancer cells. JAK-1/STAT-3 is a key intracellular signaling transduction pathway, which controls the growth, differentiation, apoptosis, invasion, and angiogenesis of various cancer cells. The present study explored the impact of allyl isothiocyanate (AITC) on the JAK-1/STAT-3 pathway in DMBA-induced rat mammary tumorigenesis. The mammary tumor was initiated through a single dose of 25 mg DMBA/rat by a subcutaneous injection administered near the mammary gland. We observed decreased body weight and increased the total number of tumors, tumor incidence, tumor volume, well-developed tumor, and histopathological abnormalities in DMBA-induced rats that were modulated after being treated with AITC. Staining of mammary tissues showed a high accumulation of collagen in DMBA-induced rats and it was normalized by the AITC treatment. Moreover, DMBA-induced mammary tissues showed up-regulated expressions of EGFR, pJAK-1, pSTAT-3, nuclear fraction of STAT-3, VEGF, VEGFR2, HIF-1α, MMP-2, and MMP-9 and the down-regulated expressions of cytosolic fraction of STAT-3 and TIMP-2. Oral administration of AITC on DMBA-induced rats inhibits angiogenesis and invasion by modifying these angiogenic and invasive markers. The finding of the present study was further confirmed by molecular docking analysis that shows a strong binding interaction between AITC with STAT-3 and cocrystal structure of STAT-3 glide energy of -18.123 and -72.246 (kcal/mole), respectively. Overall, the results suggested that AITC inhibits activation of the JAK-1/STAT-3 pathway, which subsequently prevents angiogenesis and invasion. It was recommended that AITC might develop a beneficial effect against breast cancer.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; ErbB Receptors; Molecular Docking Simulation; Neoplasms; Rats; Signal Transduction

Transient receptor potential ankyrin 1 (TRPA1) channels are expressed on the surface of different cell types, including immune cells. However, TRPA1's role in the context of innate and adaptive immune responses has not been fully elucidated so far. In this study, we aimed at investigating the expression and function of TRPA1 channels on NK cells. Among NK cells, TRPA1 was highly expressed by the CD56

Topics: CD56 Antigen; Cytotoxicity, Immunologic; Humans; K562 Cells; Killer Cells, Natural; Neoplasms; Receptors, IgG; Transient Receptor Potential Channels; TRPA1 Cation Channel