Rocaglamide enhances NK cell-mediated killing of non-small cell lung cancer cells by inhibiting autophagy

Yao, Chao; Ni, Zhongya; Gong, Chenyuan; Zhu, Xiaowen; Wang, Lixin; Xu, Zihang; Zhou, Chunxian; Li, Suyun; Zhou, Wen; C, Zou; Zhu, Shuchai

doi:10.1080/15548627.2018.1489946

Cited by 64 publications

(59 citation statements)

References 42 publications

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“…Previous studies also reported sensitizing tumors to NK cell activity by targeting alternate signaling pathways in tumors, including inhibition of BRAF (V600E) (310), STAT3 inhibition (311), and modulation of cancer cell autophagy (312,313).…”

Section: Upregulation Of Nk Cell Ligandsmentioning

confidence: 98%

Unleashing Natural Killer Cells in the Tumor Microenvironment–The Next Generation of Immunotherapy?

2020

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The emergence of immunotherapy for cancer treatment bears considerable clinical promise. Nevertheless, many patients remain unresponsive, acquire resistance, or suffer dose-limiting toxicities. Immune-editing of tumors assists their escape from the immune system, and the tumor microenvironment (TME) induces immune suppression through multiple mechanisms. Immunotherapy aims to bolster the activity of immune cells against cancer by targeting these suppressive immunomodulatory processes. Natural Killer (NK) cells are a heterogeneous subset of immune cells, which express a diverse array of activating and inhibitory germline-encoded receptors, and are thus capable of directly targeting and killing cancer cells without the need for MHC specificity. Furthermore, they play a critical role in triggering the adaptive immune response. Enhancing the function of NK cells in the context of cancer is therefore a promising avenue for immunotherapy. Different NK-based therapies have been evaluated in clinical trials, and some have demonstrated clinical benefits, especially in the context of hematological malignancies. Solid tumors remain much more difficult to treat, and the time point and means of intervention of current NK-based treatments still require optimization to achieve long term effects. Here, we review recently described mechanisms of cancer evasion from NK cell immune surveillance, and the therapeutic approaches that aim to potentiate NK function. Specific focus is placed on the use of specialized monoclonal antibodies against moieties on the cancer cell, or on both the tumor and the NK cell. In addition, we highlight newly identified mechanisms that inhibit NK cell activity in the TME, and describe how biochemical modifications of the TME can synergize with current treatments and increase susceptibility to NK cell activity.

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Section: Upregulation Of Nk Cell Ligandsmentioning

confidence: 98%

Unleashing Natural Killer Cells in the Tumor Microenvironment–The Next Generation of Immunotherapy?

2020

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“…In normal cells, autophagy has been shown to suppress malignant transformation. However, once malignant transformation has occurred, autophagy can promote tumor progression and resistance to therapy [4]. Therefore, autophagy is considered a promising therapeutic candidate for cancer treatment.…”

Section: Discussionmentioning

confidence: 99%

“…In supporting this, activation of autophagy has been shown to mediate the peritumoral monocyte‐induced cancer progression of human hepatocellular carcinoma, as well as the astrocyte‐induced promotion of breast cancer metastasis to the brain [5,10]. Of particular interest, inhibition of autophagy has been shown to mediate the natural killer cell‐induced killing of non‐small‐cell lung cancer cells [4]. Therefore, targeting autophagy is suggested as a promising strategy for cancer therapy [4,5].…”

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confidence: 99%

Alpha‐lipoic acid inhibits lung cancer growth via mTOR‐mediated autophagy inhibition

Peng

Zhang

et al. 2020

FEBS Open Bio

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Lung cancer is the leading cause of cancer‐related death, and there remains a need for novel therapies for this malignancy. Here, we examined the effects of alpha‐lipoic acid (LA), a drug used for treating human diabetic complications, on lung cancer growth. We report that LA limited lung cancer growth in xenograft mice and reduced lung cancer A549 cell viability. We observed autophagy activation in human lung cancers, and report that LA inactivated autophagy in A549 cells. In addition, LA activated mammalian target of rapamycin (mTOR)/p70S6K signaling. Inhibition of mTOR with rapamycin reversed LA‐induced inactivation of autophagy and abolished LA‐induced suppression of A549 cell viability. Altogether, the data suggest that LA exerts an anti‐lung cancer effect through mTOR‐mediated inhibition of autophagy, and thus LA may have therapeutic potential for lung cancer management.

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“…In addition, a growing body of evidence shows that Chinese herbs and its effective ingredients can exert tumor suppressive effects through multiple ways, including induction of apoptosis, anti-metastasis and anti-angiogenesis, proliferation inhibition, suppression of cancer stem-like cells, induction of autophagy, etc. [4][5][6][7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Thevebioside, the Active Ingredient of Traditional Chinese Medicine, Inhibits SRC3 Mediated Signaling by Ubiquitination to Induce NSCLC Cells Apoptosis

Yao

Zhang

et al. 2020

Preprint

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Background:The high incidence and mortality of lung cancer has been a widespread concern in the world, among which non-small cell lung cancer (NSCLC)accounts for more than 85% of lung cancer, and its 5-year prognosis is pretty poor. Accumulating studies have shown that traditional Chinese medicine (TCM) and its active ingredients have shown good anti-tumor activity. Based on the results of our previous high-throughput screening, it was the first time to find that Thevebioside (THB, an active ingredient from TCM) is sensitive to NSCLC cells, and then we will still the first to reveal the underling mechanism of its tumor suppressive activity.Methods: In this study, MTT and colony formation assay were used to detect cell growth. Annexin V/ propidium iodide, Hoechst 33342 were applied to test the process of cellular apoptosis or cell cycle arrest which determined by flow cytometry in NSCLC (A549 and H460) cells. qRT-PCR and Western blot was utilized to value the level of expression of SRC&(SRC1-3) and apoptosis related proteins. The ubiquitination degradation of SRC3 was through proteasome dependent pathway were examined by the usage of CHX and MG132 and the co-immunoprecipitation assay. The anticancer activity of THB, Neritaloside，Odoroside H and digoxin in vivo were monitored in nude mice by subcutaneous inoculation or intrapulmonary injection of A549 cells and then administrated these agents (2 mg/ kg or 4mg/kg) by intraperitoneal injection three times a week for 30 days. Tumor growth was monitored by a luciferase living imaging system. Body weight of mice and tumor volume were measured weekly. The survival carve was recorded. Pathological histology of liver, kidney and heart were detected by H&E staining, and its functions were tested by ELISA. Results：THB effectively inhibits the outgrowth of NSCLC cells (A549 and H460) by inducing cellular apoptosis. SRC-3 was significantly down-regulated after THB treatment dependent on ubiquitin-proteasome-mediated degradation, which subsequently inhibited the AKT signaling pathway to promte apoptosis. Animal study supported in vitro results, showing THB had a good suppressive effect on tumor growth. Besides, it also indicated that THB without overt cytotoxic effect on liver, kidney and heart.Conclusion：THB , as an active extract from TCM，exerted inhibitory effect on tumor growth of NSCLC by down-regulating the expression of SCR-3 rely on the ubiquitin-proteasome degradation pathway, thereby inhibiting the AKT signaling to induce cellular apoptosis , with minimal toxicity.

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Rocaglamide enhances NK cell-mediated killing of non-small cell lung cancer cells by inhibiting autophagy

Cited by 64 publications

References 42 publications

Unleashing Natural Killer Cells in the Tumor Microenvironment–The Next Generation of Immunotherapy?

Unleashing Natural Killer Cells in the Tumor Microenvironment–The Next Generation of Immunotherapy?

Alpha‐lipoic acid inhibits lung cancer growth via mTOR‐mediated autophagy inhibition

Thevebioside, the Active Ingredient of Traditional Chinese Medicine, Inhibits SRC3 Mediated Signaling by Ubiquitination to Induce NSCLC Cells Apoptosis

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