Piperlongumine induces apoptosis and autophagy in human lung cancer cells through inhibition of PI3K/Akt/mTOR pathway

Wang, Feng; Mao, Yong; You, Qingjun; Hua, Dong; Cai, Dongyan

doi:10.1177/0394632015598849

Cited by 100 publications

(67 citation statements)

References 43 publications

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“…AKT signalling has an important role in the regulation of cell proliferation, angiogenesis, migration and invasion [48]. Numerous studies revealed that mTOR kinase could suppress autophagy and apoptosis [49]. Our results demonstrated that phosphorylated AKT and phosphorylated mTOR were decreased in both breast cancer cell lines after CEP treatment.…”

Section: Discussionmentioning

confidence: 52%

Cepharanthine Induces Autophagy, Apoptosis and Cell Cycle Arrest in Breast Cancer Cells

Gao

Ding

et al. 2017

Cell Physiol Biochem

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Background: Cepharanthine (CEP) is a biscoclaurine alkaloid extracted from Stephania cepharantha and has been shown to have an anti-tumour effect on different types of cancers. However, the anti-cancer effect of CEP on human breast cancer cells is still unclear. Methods: We used MTT, clone formation, in vitro scratch, invasion and migration assays to confirm the inhibitory role of CEP on the proliferation of breast cancer cells. Flow cytometry, plasmid construction and western blot analysis were used to study the detailed mechanisms. Results: Our study showed that CEP could inhibit cell proliferation by inducing autophagy, apoptosis, and G0/G1 cell cycle arrest of breast cancer cells. Furthermore, we found that CEP induced autophagy and apoptosis by inhibiting the AKT/mTOR signalling pathway. Conclusion: We found that CEP could inhibit growth and motility of MCF-7 and MDA-MB-231 breast cancer cell. Our study revealed an anti-tumour effect of CEP on breast cancer cells and suggests that CEP could be a potential new clinical therapy for breast cancer.

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Section: Discussionmentioning

confidence: 52%

Cepharanthine Induces Autophagy, Apoptosis and Cell Cycle Arrest in Breast Cancer Cells

Gao

Ding

et al. 2017

Cell Physiol Biochem

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“…PL modulates the activity of many cell signaling and survival pathways in cancer cells [31], and a number of studies have investigated the MOA by which PL induces apoptosis in these cells [30, 35–40, 45, 54–69]. Data from these studies may be translatable to PL-induced SC apoptosis because SCs and cancer cells share some common pro-survival pathways [23].…”

Section: Discussionmentioning

confidence: 99%

Discovery of piperlongumine as a potential novel lead for the development of senolytic agents

Wang

Chang

Liu

et al. 2016

Aging

222

174

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Accumulating evidence indicates that senescent cells play an important role in many age-associated diseases. The pharmacological depletion of senescent cells (SCs) with a “senolytic agent”, a small molecule that selectively kills SCs, is a potential novel therapeutic approach for these diseases. Recently, we discovered ABT-263, a potent and highly selective senolytic agent, by screening a library of rationally-selected compounds. With this screening approach, we also identified a second senolytic agent called piperlongumine (PL). PL is a natural product that is reported to have many pharmacological effects, including anti-tumor activity. We show here that PL preferentially killed senescent human WI-38 fibroblasts when senescence was induced by ionizing radiation, replicative exhaustion, or ectopic expression of the oncogene Ras. PL killed SCs by inducing apoptosis, and this process did not require the induction of reactive oxygen species. In addition, we found that PL synergistically killed SCs in combination with ABT-263, and initial structural modifications to PL identified analogs with improved potency and/or selectivity in inducing SC death. Overall, our studies demonstrate that PL is a novel lead for developing senolytic agents.

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“…AKT can downregulate radiation-induced autophagy and apoptosis in breast cancer cells [32]. The natural alkaloid piperlongumine was shown to activate apoptosis and autophagy in lung cancer cells through inhibition of AKT/mTOR pathway [33]. The antitumor enzyme asparaginase triggers apoptosis and cytoprotective autophagy in chronic myeloid leukemia cells by inhibition of AKT/mTOR signaling pathway [34].…”

Section: Discussionmentioning

confidence: 99%

SKF-96365 activates cytoprotective autophagy to delay apoptosis in colorectal cancer cells through inhibition of the calcium/CaMKIIγ/AKT-mediated pathway

et al. 2016

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Store-operated Ca2+ entry (SOCE) inhibitors are emerging as an attractive new generation of anti-cancer drugs. Here, we report that SKF-96365, an SOCE inhibitor, exhibits potent anti-neoplastic activity by inducing cell-cycle arrest and apoptosis in colorectal cancer cells. In the meantime, SKF-96365 also induces cytoprotective autophagy to delay apoptosis by preventing the release of cytochrome c (cyt c) from the mitochondria into the cytoplasm. Mechanistically, SKF-96365 treatment inhibited the calcium/calmodulin-dependent protein kinase IIγ (CaMKIIγ)/AKT signaling cascade in vitro and in vivo. Overexpression of CaMKIIγ or AKT abolished the effects of SKF-96365 on cancer cells, suggesting a critical role of the CaMKIIγ/AKT signaling pathway in SFK-96365-induced biological effects. Moreover, Hydroxychloroquine (HCQ), an FDA-approved drug used to inhibit autophagy, could significantly augment the anti-cancer effect of SFK-96365 in a mouse xenograft model. To our best knowledge, this is the first report to demonstrate that calcium/CaMKIIγ/AKT signaling can regulate apoptosis and autophagy simultaneously in cancer cells, and the combination of the SOCE inhibitor SKF-96365 with autophagy inhibitors represents a promising strategy for treating patients with colorectal cancer.

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Piperlongumine induces apoptosis and autophagy in human lung cancer cells through inhibition of PI3K/Akt/mTOR pathway

Cited by 100 publications

References 43 publications

Cepharanthine Induces Autophagy, Apoptosis and Cell Cycle Arrest in Breast Cancer Cells

Cepharanthine Induces Autophagy, Apoptosis and Cell Cycle Arrest in Breast Cancer Cells

Discovery of piperlongumine as a potential novel lead for the development of senolytic agents

SKF-96365 activates cytoprotective autophagy to delay apoptosis in colorectal cancer cells through inhibition of the calcium/CaMKIIγ/AKT-mediated pathway

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