Inhibition of autophagy enhances cisplatin cytotoxicity in human adenoid cystic carcinoma cells of salivary glands

Ma, Ben; Liang, Liyang; Liao, Guiqing; Liang, Yujie; Liu, Haichao; Zheng, Guanghui; Su, Yu‐xiong

doi:10.1111/jop.12066

Cited by 24 publications

(21 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In certain circumstances, autophagy can promote cancer cell survival and suppress apoptosis . As we have shown previously, inhibition of autophagy increases cisplatin cytotoxicity and promotes apoptosis in ACC cells of salivary glands . However, in other cancers, induction of autophagy promotes apoptotic by chemotherapeutic drugs .…”

Section: Discussionmentioning

confidence: 74%

Role of Noxa in proliferation, apoptosis, and autophagy in human adenoid cystic carcinoma

Liang

Weng

You

et al. 2018

J Oral Pathology Medicine

View full text Add to dashboard Cite

Background: Noxa, which is subset of the Bcl-2 family of proteins, was previously reported to have considerable therapeutic potential in diverse cancers. However, its expression and role in salivary gland adenoid cystic carcinoma (ACC) have not been well studied. This study aimed to elucidate the expression and role of Noxa in salivary gland ACC. Materials and Methods:The expression levels of NOXA and its association with overall survival in salivary gland ACC were analyzed by quantitative real-time PCR.We next examined the effects of Noxa overexpression or inhibition on colony formation, proliferation, apoptosis, and autophagy of salivary gland ACC cells. Furthermore, promoter analysis was performed to identify the potential transcriptional activator of NOXA.Results: NOXA was markedly down-regulated and significantly correlated with a more aggressive phenotype and poor overall survival of salivary gland ACC. Ectopic expression of Noxa suppressed the viability and growth of ACC cells, which involved the induction of apoptosis and autophagy. Moreover, the transcriptional activity of NOXA gene could be enhanced by p53. Conclusion:The findings of this study indicate that Noxa, activated transcriptionally by p53, suppress the progression of ACC, whereby it regulates proliferation, apoptosis, and autophagy. K E Y W O R D Sadenoid cystic carcinoma, apoptosis, autophagy, cell proliferation, Noxa

show abstract

Section: Discussionmentioning

confidence: 74%

Role of Noxa in proliferation, apoptosis, and autophagy in human adenoid cystic carcinoma

Liang

Weng

You

et al. 2018

J Oral Pathology Medicine

View full text Add to dashboard Cite

show abstract

“…In contrast, autophagy can also be cytoprotective. Take recent studies as examples, autophagy induction is demonstrated to promote the survival of esophageal cancer cells following treatment with 5-FU or cisplatin (26), and autophagy inhibition by 3-MA, CQ, or si-beclin 1 increased 5-FU-or cisplatin-induced apoptosis in hepatocarcinoma cells and adenoid cystic carcinoma cells of salivary glands (27,28). In consistent with these observations, we also verified a protective role of autophagy against chemotherapeutic drugs in long-term ANE-s or 30-100 K-s cells, because both 3-MA and CQ can reduce the increased cisplatin and/or 5-FU resistance in ANE-s and 30-100 K-s cells.…”

Section: Discussionmentioning

confidence: 99%

Long‐term stimulation of areca nut components results in increased chemoresistance through elevated autophagic activity

Yen

Chiang

Liu

et al. 2013

J Oral Pathology Medicine

View full text Add to dashboard Cite

show abstract

“…The chemosensitizing effect of CQ, which is a promising strategy to improve cancer treatment, partly depends on its ability to suppress autophagy [12] . Inhibition of autophagy with 3-MA, CQ, or Beclin-1 shRNA reinforces the death of human salivary gland adenoid cystic carcinoma (ACC) cells after cis-diamminedichloroplatinum (CDDP) treatment [13] . CQ is a promising candidate for combination with chemotherapeutic agents (eg, LDM) for improving clinical outcomes through autophagy inhibition and its lysosomotropic properties.…”

Section: Introductionmentioning

confidence: 99%

Chloroquine potentiates the anti-cancer effect of lidamycin on non-small cell lung cancer cells in vitro

2014

View full text Add to dashboard Cite

Aim: To assess the synergistic actions of lidamycin (LDM) and chloroquine (CQ), a lysosomal enzyme inhibitor, in human non-small cell lung cancer (NSCLC) cells, and to elucidate the potential mechanisms. Methods: Human NSCLC cell lines A549 and H460 were treated with CQ and/or LDM. Cell proliferation was analyzed using MTT assay, and apoptosis was quantified using flow cytometry. Western blotting was used to detect the protein levels of caspase 3, PARP, Bcl-2, Bax, p53, LC3-I and LC3-II. A H460 cell xenograft model in BALB/c nude mice was used to evaluate the anticancer efficacy of CQ and LDM in vivo. Results: Both LDM and CQ concentration-dependently suppressed the proliferation of A549 and H460 cells in vitro (the IC 50 values of LDM were 1.70±0.75 and 0.043±0.026 nmol/L, respectively, while the IC 50 values of CQ were 71.3±6.1 and 55.6±12.5 μmol/L, respectively). CQ sensitized both NSCLC cell lines to LDM, and the majority of the coefficients of drug interaction (CDIs) for combination-doses were less than 1. The ratio of apoptosis of H460 cells induced by a combined treatment of CQ and LDM (77.0%±5.2%) was significantly higher than those caused by CQ (23.1%±4.2%) or by LDM (65.1%±4.1%) alone. Furthermore, the combined treatment markedly increased the cleaved PARP and cleaved caspase 3 in H460 cells, which were partly reversed by pretreatment with the caspase inhibitor zVAD.fmk. zVAD.fmk also partially reversed the inhibitory effect of the combination treatment on the proliferation of H460 cells. The combination therapy group had a notable increase in expression of Bax and a very slight decrease in expression of Bcl-2 and p53 protein. LDM alone scarcely affected the level of LC3-II in H460 cells, but slightly reduced CQ-induced LC3-II expression. 3-MA, an autophagy inhibitor also sensitized H460 cells to LDM. In nude mice bearing H460 cell xenograft, administration of LDM (25 μg/kg, iv) and CQ (60 mg/kg, ip) suppressed tumor growth by 57.14% and 73.02%, respectively. Conclusion: The synergistic anticancer effect of LDM and CQ in vitro results from activation of a caspase-dependent and p53-independent apoptosis pathway as well as inhibition of cytoprotective autophagy.

show abstract

Inhibition of autophagy enhances cisplatin cytotoxicity in human adenoid cystic carcinoma cells of salivary glands

Cited by 24 publications

References 39 publications

Role of Noxa in proliferation, apoptosis, and autophagy in human adenoid cystic carcinoma

Role of Noxa in proliferation, apoptosis, and autophagy in human adenoid cystic carcinoma

Long‐term stimulation of areca nut components results in increased chemoresistance through elevated autophagic activity

Chloroquine potentiates the anti-cancer effect of lidamycin on non-small cell lung cancer cells in vitro

Contact Info

Product

Resources

About