Last update 01 Nov 2024

JNK x Mcl-1 x mTOR x Akt

Last update 01 Nov 2024

Basic Info

Related Targets

JNKMcl-1mTOR[+1]

Drugs associated with JNK x Mcl-1 x mTOR x Akt

MPT0B392

Target

Akt x JNK x Mcl-1 x mTOR

Mechanism

Akt inhibitors [+3]

Active Org.

Taipei Medical University

Originator Org.

Taipei Medical University

Active Indication

acute leukemia

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with JNK x Mcl-1 x mTOR x Akt

100 Translational Medicine associated with JNK x Mcl-1 x mTOR x Akt

0 Patents (Medical) associated with JNK x Mcl-1 x mTOR x Akt

Literatures (Medical) associated with JNK x Mcl-1 x mTOR x Akt

01 Nov 2023·Food Science & Nutrition

A comprehensive view on the apigenin impact on colorectal cancer: Focusing on cellular and molecular mechanisms

Review

Author: Zamanian, Mohammad Yasin ; Kamiab, Zahra ; Golmohammadi, Maryam ; Ivraghi, Mehraveh Sadeghi ; Daneshvar, Siamak ; Heidari, Mahsa ; Modanloo, Mona ; Bazmandegan, Gholamreza ; Pourhosseini, Seyed Mohammad Ebrahim

AbstractColon cancer (CC) is one of the most common and deadly cancers worldwide. Oncologists are facing challenges such as development of drug resistance and lack of suitable drug options for CC treatment. Flavonoids are a group of natural compounds found in fruits, vegetables, and other plant‐based foods. According to research, they have a potential role in the prevention and treatment of cancer. Apigenin is a flavonoid that is present in many fruits and vegetables. It has been used as a natural antioxidant for a long time and has been considered due to its anticancer effects and low toxicity. The results of this review study show that apigenin has potential anticancer effects on CC cells through various mechanisms. In this comprehensive review, we present the cellular targets and signaling pathways of apigenin indicated to date in in vivo and in vitro CC models. Among the most important modulated pathways, Wnt/β‐catenin, PI3K/AKT/mTOR, MAPK/ERK, JNK, STAT3, Bcl‐xL and Mcl‐1, PKM2, and NF‐kB have been described. Furthermore, apigenin suppresses the cell cycle in G2/M phase in CC cells. In CC cells, apigenin‐induced apoptosis is increased by inhibiting the formation of autophagy. According to the results of this study, apigenin appears to have the potential to be a promising agent for CC therapy, but more research is required in the field of pharmacology and pharmacokinetics to establish the apigenin effects and its dosage for clinical studies.

01 Sep 2019·Chemico-Biological Interactions

Tetrandrine and cepharanthine induce apoptosis through caspase cascade regulation, cell cycle arrest, MAPK activation and PI3K/Akt/mTOR signal modification in glucocorticoid resistant human leukemia Jurkat T cells

Article

Author: Xu, Wencheng ; Tu, Yuanchao ; Hirano, Toshihiko ; Yamada, Haruki ; Sugiyama, Kentaro ; Tanaka, Sachiko ; Masaki, Hiroshi ; Onda, Kenji ; Wang, Xiaoqin

Tetrandrine (TET) and cepharanthine (CEP) are two bisbenzylisoquinoline alkaloids isolated from the traditional herbs. Recent molecular investigations firmly supported that TET or CEP would be a potential candidate for cancer chemotherapy. Prognosis of patients with glucocorticoid resistant T cell acute lymphoblastic leukemia (T-ALL) remains poor; here we examined the anti-T-ALL effects of TET and CEP and the underlying mechanism by using the glucocorticoid resistant human leukemia Jurkat T cell line in vitro. TET and CEP significantly inhibited cell viabilities and induced apoptosis in dose- and time-dependent manner. Further investigations showed that TET or CEP not only upregulated the expression of initiator caspases such as caspase-8 and 9, but also increased the expression of effector caspases such as caspase-3 and 6. As the important markers of apoptosis, p53 and Bax were both upregulated by the treatment of TET and CEP. However, TET and CEP paradoxically increased the expression of anti-apoptotic proteins such as Bcl-2 and Mcl-1, and activated the survival protein NF-κB, leading to high expression of p-NF-κB. Cell cycle arrest at S phase accompanied by increase in the amounts of cyclin A2 and cyclin B1, and decrease in cylcin D1 amount in cells treated with TET or CEP will be another possible mechanism. During the process of apoptosis in Jurkat T cells, treatment with TET or CEP also increased the phosphorylation of JNK and p38. The PI3K/Akt/mTOR signaling pathway modification appears to play significant role in the Jurkat T cell apoptosis induced by TET or CEP. Moreover, TET and CEP seemed to downregulate the expressions of p-PI3K and mTOR in an independent way from Akt, since these two drugs strongly stimulated the p-Akt expression. These results provide fundamental insights into the clinical application of TET or CEP for the treatment of patients with relapsed T-ALL.

01 Jan 2019·Journal of Cellular PhysiologyQ2 · BIOLOGY

Molecular characterization of autophagic and apoptotic signaling induced by sorafenib in liver cancer cells

Q2 · BIOLOGY

Article

Author: Mauriz, José L. ; González‐Gallego, Javier ; González, Raúl ; Muntané, Jordi ; Rodríguez‐Hernández, María A. ; Padillo, Francisco J. ; Álamo‐Martínez, José M. ; Fuentes, José M. ; de la Cruz, Jesús ; Navarro‐Villarán, Elena ; Del Campo, José A. ; Quiles, José L. ; Marín‐Gómez, Luís M. ; Ordóñez, Raquel ; Rodríguez‐Arribas, Mario ; de la Rosa, Ángel J. ; Gallego, Paloma ; Contreras, Laura

Sorafenib is the unique accepted molecular targeted drug for the treatment of patients in advanced stage of hepatocellular carcinoma. The current study evaluated cell signaling regulation of endoplasmic reticulum (ER) stress, c‐Jun‐N‐terminal kinase (JNK), Akt, and 5′AMP‐activated protein kinase (AMPK) leading to autophagy and apoptosis induced by sorafenib. Sorafenib induced early (3–12 hr) ER stress characterized by an increase of Ser51P‐eIF2α/eIF2α, C/EBP homologous protein (CHOP), IRE1α, and sXBP1, but a decrease of activating transcription factor 6 expression, overall temporally associated with the increase of Thr183,Tyr185P‐JNK1/2/JNK1/2, Thr172P‐AMPKα, Ser413P‐Foxo3a, Thr308P‐AKt/AKt and Thr32P‐Foxo3a/Foxo3a ratios, and reduction of Ser2481P‐mammalian target of rapamycin (mTOR)/mTOR and protein translation. This pattern was related to a transient increase of tBid, Bim EL, Beclin‐1, Bcl‐xL, Bcl‐2, autophagy markers, and reduction of myeloid cell leukemia‐1 (Mcl‐1) expression. The progressive increase of CHOP expression, and reduction of Thr308P‐AKt/AKt and Ser473P‐AKt/AKt ratios were associated with the reduction of autophagic flux and an additional upregulation of Bim EL expression and caspase‐3 activity (24 hr). Small interfering‐RNA (si‐RNA) assays showed that Bim, but not Bak and Bax, was involved in the induction of caspase‐3 in sorafenib‐treated HepG2 cells. Sorafenib increased autophagic and apoptotic markers in tumor‐derived xenograft model. In conclusion, the early sorafenib‐induced ER stress and regulation of JNK and AMPK‐dependent signaling were related to the induction of survival autophagic process. The sustained drug treatment induced a progressive increase of ER stress and PERK‐CHOP‐dependent rise of Bim EL, which was associated with the shift from autophagy to apoptosis. The kinetic of Bim EL expression profile might also be related to the tight balance between AKt‐ and AMPK‐related signaling leading to Foxo3a‐dependent BIM EL upregulation.

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