Diosgenin in Colon Cancer

The author noted that diosgenin constrains the 3-hydroxy-3-methylglutaryl CoA reductase expression and stimulates apoptosis in human colon tumor cells. Diosgenin is also a potent inhibitor of HCT-116 with growth inhibition and induction of apoptosis [39]. Diosgenin induces apoptosis via the cyclooxygenase-2 and 5-lipoxygenase pathways in HT-29 and HCT-116 [40]. The author described diosgenin’s ability to enhance 5-LOX activity; its inhibition by AA-861 notably reduces the apoptosis of colorectal tumor cells.

Moreover, colorectal carcinoma cells expressing COX-2 are less sensitive to apoptosis induced by diosgenin compared to COX-2 absent colorectal cancer cells.

The up-regulation of COX-2 expression and activity during apoptosis of diosgenin-treated HT-29 cells and pre-treatment with a COX-2 selective inhibitor noticeably sensitizes colon carcinoma cells expressing COX-2 to diosgenin-induced apoptosis but isolates HCT-116 cells [40]. The author suggested that diosgenin activates the death receptor-5 via the p38 pathway and promotes TRAIL-induced apoptosis in colon carcinoma cells. The author showed that diosgenin alone or in combination with TRAIL enhances COX-2 expression, yet the application of a COX-2 inhibitor increases apoptosis [41].

The author showed that commercial diosgenin, which is limited to 63.8 1.2 mg/ kg dry weight in the diet at 10-100 concentration over 17 weeks, results in groups of mice that, regardless of dose, had significantly less colon cancer compared to the AOM/DSS-treated mice. The study confirmed that diosgenin suppressed colon cancer by reducing colonic inflammation and serum triglyceride levels, up-regulating lipoprotein lipase, and altering multiple signaling pathways [42]. The author stated that diosgenin reduces azoxymethane-induced aberrant crypt foci development in F344 rats and induces apoptosis in HT-29 cells. Consequently, diosgenin hinders or retards ACF development during the initiation, post-initiation, and promotional stages of azoxymethane-induced rat colon tumor. The studies determined that diosgenin decreases cell growth and alters the expression of Bcl-2/caspase-3 in colon tumor cells [43].

Diosgenin deregulates p65/p50, NF-?B p38, and MAPK trail, and attenuates acute lung injury caused by lipopolysaccharide in vivo. The author noted that diosgenin significantly attenuates LPS-induced MAPK/p38 and NF-?B establishment both in vitro and in vivo following lung infection and histopathological change in the ALI model in vivo [53]. The author indicated that diosgenin suppresses telomerase activity by interrupting the expression of the hTERT gene in the lung carcinoma cell line [54]. The author proved that fenugreek extracts containing diosgenin, as well as pure diosgenin, reduce the hTERT gene expression in the A549 cell line [55]. The author demonstrated that diosgenin possesses anti-proliferative and apoptotic properties mediated via the caspase, JNK and Akt pathways in squamous cell tumor cell lines such as A431 and Hep2 [56].

The author showed that a sequence of 26-hydroxy-22-oxocholestanic frameworks, including hecogenin and diosgenin, can cause anti-proliferative and apoptotic effects on human cervical carcinoma (CaSki) cells in vitro. Both substances did not substantially alter the proliferation of fibroblast cells, and, only occasionally, stimulated peripheral blood lymphocytes to reproduce, suggestive of an immunostimulatory effect [57]. Diosgenin’s antiproliferative effect is induced through the activation of p53, rescue of apoptosis-inducing factor, and modulation of caspase-3 activity in various tumor cells. Diosgenin reduces cell growth through apoptosis and cell cycle arrest stimulation by p53 activation in various human tumor cell lines such as melanoma cells and laryngeal cancer. Furthermore, many studies have focused on the mitochondrial form, and the use of diosgenin was caspase-3 dependent, with a reduction of ??m and nuclear localization of AIF in different tumors [58].

Diosgenin reduces melanogenesis via the activation of the PI3K signalling pathway [59]. Diosgenin induces ROS-dependent autophagy and cytotoxicity through the mTOR signaling system in chronic myeloid leukemia cells. Moreover, diosgenin can concurrently induce autophagy and cytotoxicity in BaF3 –WT K562 cells. Diosgenin significantly increases ROS levels, and this oxidative stress not only generates a cytotoxic effect on in chronic myeloid leukemia cells but also stimulates autophagy which acts as a tolerance mechanism to counteract the cytotoxicity of diosgenin in chronic myeloid leukemia cells through the mTOR signaling pathway [60]. Diosgenin inhibits osteoclastogenesis, proliferation, and aggression through the deregulation of Akt/PI3K kinase formation and NF-kB-regulated gene expression [61]. The author reported that diosgenin tested measurements of tumor extent, tumor size, and tumor burden and reviewed the actions of detoxification agents. It gauged the level of lipid peroxidation by-products and antioxidants using precise colorimetric methods [62]. The author reported that diosgenin exhibits anti-invasion functions on BGC-823 cells, which are susceptible to the hypoxia stimulus. Down-regulating HIF-1? might significantly improve its effects. It is proposed that, combined with reduced HIF-1?, diosgenin might be considered as a candidate to develop clinical therapy for gastric cancer [63].

Conclusion

Compounds derived from either remedial or dietetic plant sources offer unique improvements, such as new bioactive structures, reduced toxicity, and targeted abilities in mitigating oncogenic development (Table-1). They may, thus, serve as the resource for improved therapeutic options. A vast body of preclinical research evidence suggests that diosgenin has significant potential as an anti-cancer agent. In this review, we have compiled and examined the role of diosgenin in modulating various monogenic transcription factors and intracellular molecular factors that drive tumor initiation, progression, and metastasis (Figure-3). The pharmacological aspects of diosgenin, including its extraction and analytical methodologies, provide a comprehensive database that can prove useful for researchers interested in exploring the hidden potential of this phytoconstituent. The information summarized in this review may form an integral part of the process of developing potent medications for cancer treatment.

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