Autophagy regulates resistance of non-small cell lung cancer cells to paclitaxel

Wang

The Kaohsiung J of Med Scie

et al. 2017

Gambogic acid (GA) has been shown to inhibit cancer cell proliferation, induce apoptosis, and enhance reactive oxygen species accumulation. However, whether GA could improve multidrug resistance through modulating autophagy has never been explored. We demonstrated that the combination of GA and cisplatin (CDDP) resulted in a stronger growth inhibition effect on A549 and NCI-H460 cells using the MTT assay. Furthermore, treatment with GA significantly increased autophagy in these cells. More importantly, GA-induced cell death could be largely abolished by 3-methyladenine (3-MA) or chloroquine (CQ) treatment, suggesting that GA-induced cell death was dependent on autophagy. Western blot analysis showed that GA treatment suppressed the activation of Akt, mTOR, and S6. In addition, using a GA and rapamycin combination induced more cell death compared to either GA or rapamycin alone. In summary, GA may have utility as an adjunct therapy for non-small cell lung cancer (NSCLC) patients through autophagy-dependent cell death, even when cancer cells have developed resistance to apoptosis.

Section: Discussionmentioning

confidence: 99%

Gambogic acid improves non‐small cell lung cancer progression by inhibition of mTOR signaling pathway

Wang

The Kaohsiung J of Med Scie

et al. 2017

Annals of the New York Academy of Sciences

“…miR‐30b has been reported to directly bind to Beclin 1 and greatly affects IM nucleation . miR‐216b and miR‐376b attenuate autophagy by downregulating Beclin 1. Under hypoxic conditions, HIF‐1α facilitates the expression of miR‐210, which regulates Bcl‐2–dependent autophagy .…”

Section: Molecular Regulation Of Autophagy Machinerymentioning

confidence: 99%

Molecular regulation of autophagy machinery by mTOR‐dependent and ‐independent pathways

Al‐Bari

2020

195

109

Macroautophagy is a lysosomal degradative pathway or recycling process that maintains cellular homeostasis. This autophagy involves a series of sequential processing events, such as initiation; elongation and nucleation of the isolation membrane; cargo recruitment and maturation of the autophagosome (AP); transport of the AP; docking and fusion of the AP with a late endosome or lysosome; and regeneration of the lysosome by the autophagic lysosomal reformation cycle. These events are critically coordinated by the action of a set of several key components, including autophagy‐related proteins (Atg), and regulated by intricate networks, such as mechanistic target of rapamycin (mTOR), a master regulator of autophagy, as well as mTOR‐independent signaling pathways. Among mTOR‐independent pathways, the transient receptor potential (TRP) calcium ion channel TRPML (mucolipin) subfamily is emerging as an important signaling channel to modulate lysosomal biogenesis and autophagy. This review discusses the recent advances in elucidating the molecular mechanisms and regulation of the autophagy process. Understanding these mechanisms may ultimately allow scientists and clinicians to control this process in order to improve human health.

“…Similarly, in liver cancer cells, toxic effects of another chemotherapy agent, doxorubicin, were increased when miR-101 was overexpressed (198). In lung cancer cells, miR-24 - 3p increased sensitivity to etoposide and cisplatin, miR-200b to docetaxel, miR-216B to paclitaxel, and miR-487 - 5p to temozolomide (97, 217, 224). All of the above miRNAs were shown to block autophagy in the lung cancer context.…”

Section: Autophagy Mirnas and Cancermentioning

confidence: 99%

Autophagy-Regulating microRNAs and Cancer

et al. 2017

Macroautophagy (autophagy herein) is a cellular stress response and a survival pathway that is responsible for the degradation of long-lived proteins, protein aggregates, as well as damaged organelles in order to maintain cellular homeostasis. Consequently, abnormalities of autophagy are associated with a number of diseases, including Alzheimers’s disease, Parkinson’s disease, and cancer. According to the current view, autophagy seems to serve as a tumor suppressor in the early phases of cancer formation, yet in later phases, autophagy may support and/or facilitate tumor growth, spread, and contribute to treatment resistance. Therefore, autophagy is considered as a stage-dependent dual player in cancer. microRNAs (miRNAs) are endogenous non-coding small RNAs that negatively regulate gene expression at a post-transcriptional level. miRNAs control several fundamental biological processes, and autophagy is no exception. Furthermore, accumulating data in the literature indicate that dysregulation of miRNA expression contribute to the mechanisms of cancer formation, invasion, metastasis, and affect responses to chemotherapy or radiotherapy. Therefore, considering the importance of autophagy for cancer biology, study of autophagy-regulating miRNA in cancer will allow a better understanding of malignancies and lead to the development of novel disease markers and therapeutic strategies. The potential to provide study of some of these cancer-related miRNAs were also implicated in autophagy regulation. In this review, we will focus on autophagy, miRNA, and cancer connection, and discuss its implications for cancer biology and cancer treatment.