Parthenolide induces apoptosis and autophagy through the suppression of PI3K/Akt signaling pathway in cervical cancer

Jeyamohan, Sridharan; Moorthy, Rajesh Kannan; Kannan, Mahesh Kumar; Arockiam, Antony Joseph Velanganni

doi:10.1007/s10529-016-2102-7

Cited by 74 publications

(53 citation statements)

References 25 publications

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“…Apoptosis, also known as programmed cell death, and cell cycle arrest are two important events involved in anticancer drug treatment. Apoptosis, easily triggered by many commonly used chemopreventive agents, 20 is the result of a highly complex series of events involving cell chromatin condensation, DNA fragmentation, and cell shrinkage, 21 including two major signaling pathways controlling apoptosis, the extrinsic apoptosis pathway (death receptor) and the intrinsic apoptosis pathway (mitochondrial-dependent). 22,23 Mitochondria play a crucial role in apoptotic regulation and the mitochondrial dysfunction that occurs during apoptosis.…”

Section: Discussionmentioning

confidence: 99%

<p>Acetyl-11-Keto-β-Boswellic Acid Exerts the Anti-Cancer Effects via Cell Cycle Arrest, Apoptosis Induction and Autophagy Suppression in Non-Small Cell Lung Cancer Cells</p>

Lv¹,

Shao²,

Zhang³

et al. 2020

OTT

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Objective: Acetyl-11-keto-β-boswellic acid (AKBA) is a triterpenoid, which is the main component of boswellic acid from Boswellia Serrata, a medicinal plant that has shown immense potential in anti-cancer therapy. This study aims to explore the roles and molecular mechanisms of AKBA on cell behavior in non-small cell lung cancer (NSCLC) cells. Materials and Methods: The effects of AKBA on the cell viability in A549, H460, H1299, and BEAS-2B cells were determined by the CCK-8 assay. The colony formation assay was used to identify the effects of AKBA on cell proliferation. Potential roles of AKBA in regulating the cell cycle, apoptosis, and autophagy in A549 were evaluated by flow cytometry, Western blotting, reverse transcription-polymerase chain reaction (PCR) and immunofluorescence (IF). Results: AKBA reduced cell viability in A549, H460, H1299, and BEAS-2B. In A549 cells, AKBA suppressed the clone formation, arrested the cell cycle at the G 0 /G 1 phase, induced cellular apoptosis. We found that AKBA suppressed the formation of autolysosome, and decreased the expression levels of Beclin-1, LC3A/B-I, and LC3A/B-II proteins. Furthermore, AKBA also inhibited the expression levels of PI3K/Akt signaling pathway proteins. Conclusion: AKBA exerts the anti-cancer effects via cell cycle arrest, apoptosis induction, and autophagy suppression in NSCLC cells. This body of evidence supports the potential of AKBA as a promising drug in the treatment of NSCLC.

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Section: Discussionmentioning

confidence: 99%

<p>Acetyl-11-Keto-β-Boswellic Acid Exerts the Anti-Cancer Effects via Cell Cycle Arrest, Apoptosis Induction and Autophagy Suppression in Non-Small Cell Lung Cancer Cells</p>

Lv¹,

Shao²,

Zhang³

et al. 2020

OTT

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“…Moreover, this natural product belongs to the broader family of sesquiterpene lactones (estimated at > 5000 members), many members of which are also cytotoxic and have been hypothesized or shown to act through covalent mechanisms (Coricello et al, 2018;Quintana and Estévez, 2019). Parthenolide impairs cancer pathogenicity or confers chemotherapy or radiation sensitivity across a wide range of cancer types, including leukemia, colorectal, glioblastoma, cervical, liver, prostate, lung, pancreatic, skin, and breast cancers (Anderson and Bejcek, 2008;Carlisi et al, 2016;Diamanti et al, 2013;Jeyamohan et al, 2016;Kim et al, 2012Kim et al, , 2017Lesiak et al, 2010;Lin et al, 2017;Liu et al, 2017;Morel et al, 2017;Ralstin et al, 2006;Sun et al, 2007;Sweeney et al, 2005). Despite possessing multi-target activity and exhibiting cytotoxicity across a wide range of human cancers, parthenolide is remarkably well-tolerated in humans (Curry et al, 2004).…”

Section: Main Textmentioning

confidence: 99%

Parthenolide Covalently Targets and Inhibits Focal Adhesion Kinase in Breast Cancer Cells

Berdan¹,

Ho²,

Lehtola³

et al. 2019

Preprint

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Parthenolide, a natural product from the feverfew plant and member of the large family of sesquiterpene lactones, exerts multiple biological and therapeutic activities including anti-inflammatory and anti-cancer effects. Herein, we further study parthenolide mechanism of action using activity-based protein profiling (ABPP)-based chemoproteomic platforms to map additional covalent targets engaged by parthenolide in human breast cancer cells. We find that parthenolide, as well as other related exocyclic methylene lactonecontaining sesquiterpenes, covalently modify cysteine 427 (C427) of focal adhesion kinase 1 (FAK1) leading to impairment of FAK1-dependent signaling pathways and breast cancer cell proliferation, survival, and motility.These studies reveal a novel functional target exploited by members of a large family of anticancer natural products.

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“…22 In addition, parthenolide can induce apoptosis and autophagy-mediated growth inhibition in HeLa cells by suppressing the PI3K/Akt signaling pathway and mitochondrial membrane depolarization and ROS generation. 23 Likewise, to provide theoretical basis for the treatment of CC, the main objective of our study is to obtain evidence of role of miR-383 regulating PARP2 and PI3K-AKT-MTOR signaling pathway in the progression of CC. patients included 38 cases at phase I, 40 cases at phase II, 22 cases at phase III, 15 cases at phase IV; degree of differentiation: 48 cases of high differentiation, 35 cases of moderate differentiation, 32 cases of poor differentiation.…”

mentioning

confidence: 99%

RETRACTED: microRNA‐383 suppresses the PI3K‐AKT‐MTOR signaling pathway to inhibit development of cervical cancer via down‐regulating PARP2

Teng

Jiao

Hao

et al. 2018

J of Cellular Biochemistry

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This study aims to evaluate the effect of the regulatory relationship between microRNA-383 (miR-383) and PARP2 in the cell migration and invasion in human with cervical cancer (CC) via the PI3K-AKT-MTOR signaling pathway. Cancerous tissues and corresponding paracancerous tissues were collected from 115 patients with CC. The positive expression rate of PARP2 was detected by immunohistochemistry. HeLa cells with highest miR-383 expression were selected and assigned into the blank, negative control (NC), miR-383 mimic, miR-383 inhibitor, si-PARP2, and miR-383 inhibitor + si-PARP2 groups. qRT-PCR and Western blot were performed to evaluate the expression of miR-383, PI3K, AKT, mTOR, PARP2, and p70S6K. MTT assay were utilized to measure cell viability. Transwell assay were applied to evaluate cell invasion and metastasis. Dual luciferase reporter assay identified that PARP2 is a target gene of miR-383. Cancerous tissues manifested higher expression of PI3K, AKT, mTOR, PARP2, and p70S6K but lower miR-383 expression than paracancerous tissues. Compared with the blank and NC groups, the miR-383 mimic and si-PARP2 groups had decreased expression of PI3K, AKT, mTOR, PARP2, and p70S6K mRNA and protein. In the miR-383 mimic and si-PARP2 groups, the cell viability, migration, and invasion were descended, in comparison to the blank and NC groups. All above parameters showed an opposite trend in the miR-383 inhibitor group when compared with the blank and NC groups. This study demonstrates that miR-383 could down-regulate PARP2 to protect against CC by inhibiting PI3K-AKT-MTOR signaling pathway.

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Parthenolide induces apoptosis and autophagy through the suppression of PI3K/Akt signaling pathway in cervical cancer

Abstract: Parthenolide induces apoptosis and autophagy-mediated growth inhibition in HeLa cells by suppressing the PI3K/Akt signaling pathway and mitochondrial membrane depolarization and ROS generation. Parthenolide may be a potential therapeutic agent for the treatment of cervical cancer.

Cited by 74 publications

References 25 publications

<p>Acetyl-11-Keto-β-Boswellic Acid Exerts the Anti-Cancer Effects via Cell Cycle Arrest, Apoptosis Induction and Autophagy Suppression in Non-Small Cell Lung Cancer Cells</p>

<p>Acetyl-11-Keto-β-Boswellic Acid Exerts the Anti-Cancer Effects via Cell Cycle Arrest, Apoptosis Induction and Autophagy Suppression in Non-Small Cell Lung Cancer Cells</p>

Parthenolide Covalently Targets and Inhibits Focal Adhesion Kinase in Breast Cancer Cells

RETRACTED: microRNA‐383 suppresses the PI3K‐AKT‐MTOR signaling pathway to inhibit development of cervical cancer via down‐regulating PARP2

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