GFRA1 promotes cisplatin-induced chemoresistance in osteosarcoma by inducing autophagy

Kim, Mihwa; Jung, Ji Yeon; Choi, Seungho; Lee, Hyunseung; Morales, Liza D.; Koh, Joon; Kim, Sun Hun; Choi, Yoo Duk; Choi, Chan; Slaga, Thomas J.; Kim, Won Jae; Kim, Dae Joon

doi:10.1080/15548627.2016.1239676

Cited by 138 publications

(138 citation statements)

References 60 publications

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“…In response to adverse stress, such as nutrient starvation, autophagy may be triggered for the degradation of unnecessary molecules, serving as a potential survival mechanism to maintain intercellular homeostasis, regulate the immune response and remodel development (32,33). Studies suggest that autophagy induction is a mechanism of chemoresistance (34,35). On the contrary, numerous anticancer agents, such as resveratrol, induce autophagic cell death, indicating that autophagy may be a vital mechanism for anticancer therapy (36).…”

Section: Discussionmentioning

confidence: 99%

Autophagy induction enhances tetrandrine-induced apoptosis via the AMPK/mTOR pathway in human bladder cancer cells

Kou

Liu

et al. 2017

Oncology Reports

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Tetrandrine, a bisbenzylisoquinoline alkaloid isolated from the roots of Stephania tetrandra is a traditional Chinese medicine and exerts anticancer capacity in various types of cancers. Previous studies have shown that tetrandrine induces apoptosis in bladder cancer cells via activation of the caspase cascade. However, the underlying mechanism has not yet been reported. Autophagy is a cellular process involved in the degradation of broken proteins and aging organelles to maintain homeostasis. Recent studies indicate that autophagy is implicated in cancer therapy. Thus, we focused on the correlation between autophagy and apoptosis upon tetrandrine treatment in human bladder cancer cells. Firstly, our results observed a marked increase in autophagic double-membrane vacuoles and fluorescent puncta of red fluorescence protein-green fluorescence protein-LC3 (GRP-RFP-LC3) upon tetrandrine treatment, as evidenced by transmission electron microscopy and confocal fluorescence microscopy. Secondly, the expression of LC3-II was increased in tetrandrine-treated T24 and 5637 cells in a time- and concentration-dependent manner. Subsequently, downregulation of p62 and LC3 turnover assay further confirmed that tetrandrine induced autophagic flux in bladder cancer T24 and 5637 cells. Thirdly, the protein levels of phosphorylated-AMP-activated protein kinase (AMPK) and phosphorylated-acetyl-coenzyme A carboxylase (ACC) were upregulated in the tetrandrine-treated cells, while the mammalian target of rapamycin (mTOR)-related proteins were downregulated. Moreover, AICAR, a common AMPK activator, further increased the expression the LC3-II, while AMPK inhibitor compound C partially reversed the LC3-II protein levels in bladder cancer T24 cells. Finally, AICAR significantly reinforced the growth inhibition and apoptosis induction of tetrandrine in T24 and 5637 cells, while compound C had an opposite effect, suggesting that AMPK-mediated autophagy enhanced the cytotoxic and pro-apoptosis effect of tetrandrine in human bladder cancer cells. Taken together, the present study showed that tetrandrine induced autophagy in human bladder cancer cells by regulating the AMPK/mTOR signaling pathway, which contributed to the apoptosis induction by tetrandrine, indicating that tetrandrine may be a potential anticancer candidate for the treatment of bladder cancer, and autophagy may be a possible mechanism for cancer therapy.

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Section: Discussionmentioning

confidence: 99%

Autophagy induction enhances tetrandrine-induced apoptosis via the AMPK/mTOR pathway in human bladder cancer cells

Kou

Liu

et al. 2017

Oncology Reports

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“…Autophagy has been claimed to play a paradoxical role in controlling cell death and survival in response to various stimuli [27]. Previous studies have reported that induction of autophagy could promote cisplatin-induced chemoresistance in osteosarcoma [28]. To investigate the role of CDDPor PLB-induced autophagy, the inhibitor 3-methyladenine (3-MA, inhibitor of early autophagy/LC3-II accumulation) was used to pretreat TSCC cells.…”

Section: Plumbagin Enhanced the Proapoptosis Effect Of Cisplatin In Tmentioning

confidence: 99%

Plumbagin Enhances the Anticancer Efficacy of Cisplatin by Increasing Intracellular ROS in Human Tongue Squamous Cell Carcinoma

Xue

Pan

Zhou

et al. 2020

Oxidative Medicine and Cellular Longevity

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Cisplatin is widely used in the treatment of tongue squamous cell carcinoma (TSCC), but its clinical efficacy is limited by drug resistance and toxic side effects. Hence, a novel compound capable of enhancing the anticancer effect of cisplatin while reducing the side effects is urgently needed. We have previously shown that plumbagin (PLB), an anticancer phytochemical, is able to inhibit the growth of TSCC in vitro and in vivo. The objective of this study was to investigate the effect of PLB in reversing the resistance of TSCC to cisplatin as well as its molecular mechanisms. Here, we found that PLB enhances cisplatin-induced cytotoxicity, apoptosis, and autophagy in CAL27 and cisplatin-resistant CAL27/CDDP cells. PLB could inhibit the viability and growth of TSCC cells by increasing the production of intracellular reactive oxygen species (ROS). In addition, the combination treatment of PLB and cisplatin resulted in a synergistic inhibition of TSCC viability, apoptosis, and autophagy by increasing intracellular ROS, which may be achieved by activating JNK and inhibiting AKT/mTOR signaling pathways. Finally, the synergistic treatment was also demonstrated in vivo. Therefore, PLB combined with cisplatin is a potential therapeutic strategy against therapy TSCC cisplatin resistance.

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“…The second BC group is composed by highly expressed genes including SMAD2, SMAD4, TCF12, ELP2, ATG2B, PIGN, MBP, NCBP3 and PIK3C3, which enrich pathways of cell cycle, cell metabolism regulation, TGF-beta signaling, PI3K cascade, autophagy, immune responses and mRNA production regulation. The third BC group is enriched by a large number of pseudo genes and the protein coding genes in this group enrich the translation regulation and viral infection, in which genes TMA7, DEXI and EIF3CL have been previously reported as related to cisplatin and fluorouracil resistance in bladder and gastric cancer (30, 31). In addition, the four BCs group are also enriched by two different groups of ribosome proteins, which are related to translational control and elongation of peptides.…”

Section: Resultsmentioning

confidence: 99%

Bi-clustering based biological and clinical characterization of colorectal cancer in complementary to CMS classification

Cao

Chang

Wan

et al. 2018

Preprint

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GFRA1 promotes cisplatin-induced chemoresistance in osteosarcoma by inducing autophagy

Cited by 138 publications

References 60 publications

Autophagy induction enhances tetrandrine-induced apoptosis via the AMPK/mTOR pathway in human bladder cancer cells

Autophagy induction enhances tetrandrine-induced apoptosis via the AMPK/mTOR pathway in human bladder cancer cells

Plumbagin Enhances the Anticancer Efficacy of Cisplatin by Increasing Intracellular ROS in Human Tongue Squamous Cell Carcinoma

Bi-clustering based biological and clinical characterization of colorectal cancer in complementary to CMS classification

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