VASH2 Promotes Cell Proliferation and Resistance to Doxorubicin in Non-Small Cell Lung Cancer via AKT Signaling

Tan, Xiangbin; Liao, Ze-fei; Zou, Shuangyou; Ma, Liangyun; Wang, Aimin

doi:10.3727/096504019x15509383469698

Cited by 12 publications

(7 citation statements)

References 24 publications

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“…Furthermore, reducing activity of drug transporters such as P-gp elevates DOX accumulation in cancer cells and is of importance in reversing chemoresistance [88]. Overall, studies are in agreement with the fact that different molecular pathways and mechanisms can involve in inducing DOX chemoresistance and phytochemical are potential agents in triggering chemosensitivity [89][90][91][92].…”

Section: Doxorubicin: Cancer Resistance and Side Effectssupporting

confidence: 68%

Polychemotherapy with Curcumin and Doxorubicin via Biological Nanoplatforms: Enhancing Antitumor Activity

et al. 2020

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Doxorubicin (DOX) is a well-known chemotherapeutic agent extensively applied in the field of cancer therapy. However, similar to other chemotherapeutic agents such as cisplatin, paclitaxel, docetaxel, etoposide and oxaliplatin, cancer cells are able to obtain chemoresistance that limits DOX efficacy. In respect to dose-dependent side effect of DOX, enhancing its dosage is not recommended for effective cancer chemotherapy. Therefore, different strategies have been considered for reversing DOX resistance and diminishing its side effects. Phytochemical are potential candidates in this case due to their great pharmacological activities. Curcumin is a potential antitumor phytochemical isolated from Curcuma longa with capacity of suppressing cancer metastasis and proliferation and affecting molecular pathways. Experiments have demonstrated the potential of curcumin for inhibiting chemoresistance by downregulating oncogene pathways such as MMP-2, TGF-β, EMT, PI3K/Akt, NF-κB and AP-1. Furthermore, coadministration of curcumin and DOX potentiates apoptosis induction in cancer cells. In light of this, nanoplatforms have been employed for codelivery of curcumin and DOX. This results in promoting the bioavailability and internalization of the aforementioned active compounds in cancer cells and, consequently, enhancing their antitumor activity. Noteworthy, curcumin has been applied for reducing adverse effects of DOX on normal cells and tissues via reducing inflammation, oxidative stress and apoptosis. The current review highlights the anticancer mechanism, side effects and codelivery of curcumin and DOX via nanovehicles.

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Section: Doxorubicin: Cancer Resistance and Side Effectssupporting

confidence: 68%

Polychemotherapy with Curcumin and Doxorubicin via Biological Nanoplatforms: Enhancing Antitumor Activity

et al. 2020

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“…That is why molecular pathways that promote cancer cell growth and viability, can induce DOX resistance. For instance, in non-small cell lung cancer, vasohibin2 (VASH2) functions as a tumor-promoting factor in enhancing proliferation that subsequently, stimulates DOX resistance [12]. Identification of such factors is of importance in suppressing DOX resistance by developing potential therapeutics for their targeting [13].…”

Section: Introductionmentioning

confidence: 99%

Nrf2 Signaling Pathway in Chemoprotection and Doxorubicin Resistance: Potential Application in Drug Discovery

et al. 2021

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Doxorubicin (DOX) is extensively applied in cancer therapy due to its efficacy in suppressing cancer progression and inducing apoptosis. After its discovery, this chemotherapeutic agent has been frequently used for cancer therapy, leading to chemoresistance. Due to dose-dependent toxicity, high concentrations of DOX cannot be administered to cancer patients. Therefore, experiments have been directed towards revealing underlying mechanisms responsible for DOX resistance and ameliorating its adverse effects. Nuclear factor erythroid 2-related factor 2 (Nrf2) signaling is activated to increase levels of reactive oxygen species (ROS) in cells to protect them against oxidative stress. It has been reported that Nrf2 activation is associated with drug resistance. In cells exposed to DOX, stimulation of Nrf2 signaling protects cells against cell death. Various upstream mediators regulate Nrf2 in DOX resistance. Strategies, both pharmacological and genetic interventions, have been applied for reversing DOX resistance. However, Nrf2 induction is of importance for alleviating side effects of DOX. Pharmacological agents with naturally occurring compounds as the most common have been used for inducing Nrf2 signaling in DOX amelioration. Furthermore, signaling networks in which Nrf2 is a key player for protection against DOX adverse effects have been revealed and are discussed in the current review.

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“…Downregulation of stemness/EMT pathways like Notch-1 and Wnt/β-catenin, alongside of downregulation of STAT3, a well-known p38 downstream target, avoided doxorubicin-resistance in enriched CD44 − /CD24 + subpopulation of MCF-7 37 . Pharmacological downregulation of AKT, another p38 downstream target, also reduced doxorubicin resistance in non-small cell lung cancer 38 . Yet, downregulation of STAT3 and Bcl-2 by miRNA reduced doxorubicin-resistance in breast cancer 39 , 40 .…”

Section: Discussionmentioning

confidence: 97%

Translocation of intracellular CD24 constitutes a triggering event for drug resistance in breast cancer

Huth

Castro-Gomes

Góes

et al. 2021

Sci Rep

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The capacity of tumor cells to shift dynamically between different states could be responsible for chemoresistance and has been commonly linked to the acquisition of stem cell properties. Here, we have evaluated the phenotype switching associated with drug resistance in breast cancer cell lines and cell lineage obtained from Brazilian patients. We have highlighted the role of the cancer stem cell marker CD24 in the dynamics of cell plasticity and the acquirement of drug resistance. We showed that the translocation of CD24 from cytosol to cell membrane is a triggering event for the phenotype change of breast tumor cells exposed to drug stress. Here, we provide evidence that the phenotype switching is due to the presence of a cytosolic pool of CD24. Importantly, the cellular localization of CD24 was correlated with the changes in the dynamics of p38 MAPK activation. A strong and continuous phosphorylation of the p38 MAPK led to the overexpression of Bcl-2 after treatment in persistent cells presenting high density of CD24 on cell membrane. This phenotype enabled the cells to enter in slow-down of cell cycle, after which several weeks later, the dormant cells proliferated again. Importantly, the use of a p38 activity inhibitor sensitized cells to drug treatment and avoided chemoresistance.

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VASH2 Promotes Cell Proliferation and Resistance to Doxorubicin in Non-Small Cell Lung Cancer via AKT Signaling

Cited by 12 publications

References 24 publications

Polychemotherapy with Curcumin and Doxorubicin via Biological Nanoplatforms: Enhancing Antitumor Activity

Polychemotherapy with Curcumin and Doxorubicin via Biological Nanoplatforms: Enhancing Antitumor Activity

Nrf2 Signaling Pathway in Chemoprotection and Doxorubicin Resistance: Potential Application in Drug Discovery

Translocation of intracellular CD24 constitutes a triggering event for drug resistance in breast cancer

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