A730069N07Rik Activators

Chemical activators of DLC1 employ various molecular mechanisms to enhance its tumor suppressor function. Genistein, a tyrosine kinase inhibitor, can lead to the activation of DLC1 by inhibiting tyrosine kinases that act as negative regulators of DLC1's activity. This, in turn, allows DLC1 to exert its effects through its Rho-GAP domain. Similarly, resveratrol can activate DLC1 through the stimulation of AMP-activated protein kinase (AMPK), which has downstream effects, including the activation of DLC1. Epigallocatechin gallate (EGCG) contributes to the activation of DLC1 by inhibiting the PI3K/Akt pathway, which is known to phosphorylate and inhibit DLC1. By blocking this pathway, EGCG promotes DLC1 activation. Furthermore, curcumin activates DLC1 by inhibiting the NF-kB pathway, which otherwise suppresses the expression of tumor suppressor proteins including DLC1. Sulforaphane, by activating Nrf2, leads to the activation of antioxidant response elements that can trigger the activation of tumor suppressor proteins like DLC1.

In addition to the above mechanisms, quercetin can activate DLC1 by inhibiting Src family kinases, which may otherwise phosphorylate and inactivate DLC1. Silibinin contributes to DLC1 activation by inhibiting the STAT3 pathway, lifting the suppressive effects on DLC1. Indole-3-carbinol promotes DLC1 activation through the modulation of estrogen receptor signaling, which is connected to the regulation of DLC1. Caffeic acid phenethyl ester (CAPE) enhances DLC1's activity by blocking the activation of NF-kB, a regulator of tumor suppressor proteins. Capsaicin's role in DLC1 activation is associated with its modulation of calcium influx, which impacts calcium-dependent signaling pathways that regulate DLC1. Ellagic acid facilitates DLC1 activation by preventing the interaction between DLC1 and its negative regulators, thus stabilizing DLC1. Lastly, withaferin A induces DLC1 activation by inducing oxidative stress, which affects the signaling pathways that control the function of tumor suppressor proteins like DLC1.