A Review on Pharmacological and Analytical Aspects of Diosgenin

The author declared that diosgenin restrains STAT3 signaling pathways, leading to inhibition of multiplication and chemosensitization of liver tumor cells (31). Overexpression of active STAT3 releases diosgenin, tempted to induce apoptosis. Moreover, diosgenin causes the aggregation of cells in the G1 stage of the cell cycle and triggers caspase-3, causing PARP cleavage in HCC [31]. Diosgenin reduces the expression of STAT3-regulated genes including Bcl-2, Mcl-1, cyclin D1, Bcl-2, and VEGF. It also suppresses proliferation, enhances cell accumulation in the G1/G0 state, and significantly potentiates the apoptotic effects of doxorubicin and paclitaxel in liver tumor cells [31].

In 2015, it was revealed that diosgenin induces G2/M cell cycle arrest and apoptosis in liver tumor cells, reducing the proliferation of SMMC-7721, HepG2, and Bel-7402 cells in a dose-dependent manner [32]. In addition, diosgenin exerts an anti-proliferative effect, inducing G2/M cell cycle arrest and apoptosis in three liver cancer cells (32). There is strong evidence of diosgenin’s growth-inhibitory activity against liver cancer cells. Another author noted that the up-regulation of cell cycle-related proteins, p27 and p21, and activation of the caspase cascade may be involved in diosgenin-induced apoptosis and cell cycle arrest (32). Diosgenin induces apoptosis in HepG2 cells through the generation of ROS species and the mitochondrial pathway. Diosgenin-induced apoptosis in liver tumor cells occurs through the Bcl-2 protein family-mediated mitochondria/caspase-3-dependent pathway. Additionally, diosgenin-generated reactive oxygen species and oxidative stress may lead to apoptosis during the activation of ASK1, crucial upstream signals for MAPK, JNK/p38 activation in liver tumor cells (33). Diosgenin also has a role in breast cancer treatment, as it reduces the movement of human breast tumor cells by suppressing Vav2 activity (34).

The author declared that diosgenin reduces Cdc42 activation and that Cdc42 plays a pivotal role in regulating actin cytoskeleton dynamics and pseudopodia formation [34]. The author reported that diosgenin targets Akt-mediated prosurvival signaling in human BCa cells [35]. Diosgenin arrests the G0/G1 cell-cycle in breast tumor cells and silences in vivo and in vitro tumor models. Diosgenin suppresses the Akt signaling without disturbing PI3k activity in BCa cells. Diosgenin also down-regulates the expression of pAkt in the breast tumor cell line. It eliminates the /ERK Raf/ MEK pathway in breast tumor cells. The author revealed that in MCF-7 cells diosgenin reduces the entire Raf/MEK pathway, particularly pMEKs, MEKK-1, Raf, MEK-4 and MEK-1[35].

The author projected stimulation of apoptosis by a newly produced diosgenyl saponin, which reticently interferes with the estrogen receptor-a in breast tumor cells. This compound interferes with ER-a-mediated transcriptional signaling by reducing mRNA and protein expression of ER and ER-ERE binding force. Moreover, the extracellular reduction of ER signaling reduces the Src/ MAPK pathway and induces apoptosis in the extrinsic system in ER-positive MCF-7 cells [36]. BCa stem-like cells are suppressed by diosgenin, a steroidal saponin, by contracting the Wnt b-catenin signaling through the Wnt antagonist concealed frizzled-linked protein-4 [37]. The author reported that diosgenin inhibits unique properties of mammosphere shape and ALDH CD44 expression in cancer stem cells. Apoptotic causes of diosgenin can be followed by down-regulation of drug effluxes, diverting the Wnt-b catenin pathway.

The author delves deeper into the mechanism of procedure of diosgenin at the molecular level, understanding the role of Wnt-b-catenin signaling consistent with the expression of stemness traits, including self- transformation and drug resistance. Traits that contribute to combativeness and invasion, such as the EMT and pro-invasive indicator, were abolished in diosgenin action in the cell model up-regulation Wnt antagonist [37]. The author proposed that over expression of fatty acid synthesis in HER2 is inhibited by diosgenin in breast cancer cells, via modulating Akt, JNK, and mTOR phosphorylation. Diosgenin preferentially represses propagation and induces apoptosis in the HER2-overexpressing tumor cell and also inhibits the phosphorylation of Akt/mTOR in diosgenin. It also improves phosphorylation of JNK. Moreover, the author reported that the exploitation of pharmacological inhibitors revealed that the modulation of Akt/mTOR and JNK phosphorylation is necessary for diosgenin-induced FAS repression [38].

Did you like this example?

1071

45