Indole Hydrazide Compound IHZ-1 Induces Apoptosis and Autophagy via Activation of ROS/JNK Pathway in Hepatocellular Carcinoma

Sun, M. J.; Liú, Dan; Yang, Yuan; Dan, Juhua; Jia, Shuting; Luo, Ying; Liu, Jing

doi:10.3389/fonc.2022.811747

Cited by 2 publications

(3 citation statements)

References 25 publications

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“…JNK has been shown to be an essential mediator of the induction of autophagy by various anticancer drugs. 43,44 Thus, P-JNK and JNK levels in MCF-7 cells after exposure to different concentrations (1.25, 2.50, 5.00, and 10.00 μM) and durations (6,12,24, and 48 h) of compound 21o treatment, as shown in Figure 11 b−e, activated the JNK signaling pathway in a concentration-and time-dependent manner.…”

Section: ■ Results and Discussionmentioning

confidence: 91%

Scaffold Hopping of Pristimerin Provides Derivatives Containing a Privileged Quinoxaline Substructure as Potent Autophagy Inducers in Breast Cancer Cells

Fu,

Jiao,

Feng

et al. 2024

J. Nat. Prod.

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Pristimerin is a natural triterpenoid that has received much attention from medicinal chemists for its multiple biological activities. However, structural modifications of pristimerin, especially those aimed at discovering antitumor agents, are relatively limited. In this study, two series of pristimerin derivatives containing phenyloxazole and quinoxaline moieties, respectively, were designed via the scaffold hopping strategy. The target compounds were synthesized and analyzed for their cytotoxic activities in vitro using the MTT assay. The most potent cytotoxic compound (21o) significantly inhibited the proliferation of MCF-7 cells with an IC50 value of 2.0 μM, 1.5-fold more potent than pristimerin (IC50 = 3.0 μM). Compared with pristimerin, compound 21o displayed the greatest improvement in selectivity (25.7-fold) against the MCF-7 and MCF-10A cell lines. Transmission electron microscopy, monodansylcadaverine and DCFH-DA staining, Western blotting, and different inhibitor assays were performed to elucidate the mechanism of action of compound 21o. Compound 21o induced autophagy-mediated cell death in MCF-7 cells by activating the ROS/JNK signaling pathway. Therefore, incorporating a quinoxaline substructure into pristimerin could be advantageous for enhancing its cytotoxic activity. Compound 21o may serve as a lead compound for developing new therapies to treat breast cancer.

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Section: ■ Results and Discussionmentioning

confidence: 91%

Scaffold Hopping of Pristimerin Provides Derivatives Containing a Privileged Quinoxaline Substructure as Potent Autophagy Inducers in Breast Cancer Cells

Fu,

Jiao,

Feng

et al. 2024

J. Nat. Prod.

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“…Chemotherapeutic drugs are also known to kill cancer cells via other different mechanisms, including autophagic cell death, mitotic catastrophe, senescence, ferroptosis, necroptosis, etc. ( Galluzzi et al, 2018 ; Sun et al, 2022 ). Quercetin induces cell death via different mechanisms, the most common of which is triggering apoptosis.…”

Section: Therapeutic Mechanisms Of Quercetin Targeting Non-apoptotic ...mentioning

confidence: 99%

“…The ultimate goal of all these therapies is to regulate the survival or death of cancer cells, and anti-cancer drugs can kill clonogenic malignant cells by regulating various cell death modes, such as apoptosis, autophagy, senescence, mitotic catastrophe, ferroptosis, necroptosis, etc. ( Galluzzi et al, 2018 ; Sun et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

Targeting of non-apoptotic cancer cell death mechanisms by quercetin: Implications in cancer therapy

Yang

Xu²,

Tang³

et al. 2022

Front. Pharmacol.

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The ultimate goal of cancer treatment is to kill cancer cells, based on the use of various therapeutic agents, such as chemotherapy, radiotherapy, or targeted therapy drugs. Most drugs exert their therapeutic effects on cancer by targeting apoptosis. However, alterations in apoptosis-related molecules and thus assisting cells to evade death, eventually lead to tumor cell resistance to therapeutic drugs. The increased incidence of non-apoptotic cell death modes such as induced autophagy, mitotic catastrophe, senescence, and necrosis is beneficial to overcoming multidrug resistance mediated by apoptosis resistance in tumor cells. Therefore, investigating the function and mechanism of drug-induced non-apoptotic cell death modes has positive implications for the development of new anti-cancer drugs and therapeutic strategies. Phytochemicals show strong potential as an alternative or complementary medicine for alleviating various types of cancer. Quercetin is a flavonoid compound widely found in the daily diet that demonstrates a significant role in inhibiting numerous human cancers. In addition to direct pro-tumor cell apoptosis, both in vivo and in vitro experiments have shown that quercetin exerts anti-tumor properties by triggering diverse non-apoptotic cell death modes. This review summarized the current status of research on the molecular mechanisms and targets through which quercetin-mediated non-apoptotic mode of cancer cell death, including autophagic cell death, senescence, mitotic catastrophe, ferroptosis, necroptosis, etc.

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Indole Hydrazide Compound IHZ-1 Induces Apoptosis and Autophagy via Activation of ROS/JNK Pathway in Hepatocellular Carcinoma

Cited by 2 publications

References 25 publications

Scaffold Hopping of Pristimerin Provides Derivatives Containing a Privileged Quinoxaline Substructure as Potent Autophagy Inducers in Breast Cancer Cells

Scaffold Hopping of Pristimerin Provides Derivatives Containing a Privileged Quinoxaline Substructure as Potent Autophagy Inducers in Breast Cancer Cells

Targeting of non-apoptotic cancer cell death mechanisms by quercetin: Implications in cancer therapy

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