Chemoresistance of Cancer Cells: Requirements of Tumor Microenvironment-mimicking <i>In Vitro</i> Models in Anti-Cancer Drug Development

Jo, Yeonho; Choi, Nakwon; Kim, Kyobum; Koo, Hyung‐Jun; Choi, Jonghoon; Kim, Hong Nam

doi:10.7150/thno.29098

Cited by 150 publications

(130 citation statements)

References 191 publications

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“…A previous study indicated, 3D multicellular spheroid-based assays have been used for studying tumor growth [34,35]. We measured the potency of MHY2245 or DOX to inhibit the growth of SKOV3 cells in 3D spheroidal models.…”

Section: Mhy2245 Inhibits Human Ovarian Cell Tumors In Xenograft Modelsmentioning

confidence: 99%

A new SIRT1 inhibitor, MHY2245, induces autophagy and inhibits energy metabolism via PKM2/mTOR pathway in human ovarian cancer cells

Tae¹,

Son²,

Lee³

et al. 2020

Int. J. Biol. Sci.

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Ovarian cancer is a common gynecological cancer that is found worldwide. Class III histone deacetylase (HDAC) inhibitors, a new class of anticancer agents, induce autophagy in various human cancer cells. The aim of the present study was to investigate the antitumor activity of MHY2245, a new synthetic SIRT inhibitor, on human ovarian cancer cells. We found that MHY2245 exhibited potent cytotoxicity to SKOV3 cells in a time-and concentration-dependent manner. The cytotoxicity of MHY2245 (IC 50 =0.32 µM) was higher than that of doxorubicin (DOX, IC 50 =1.38µM) against SKOV3 cells. MHY2245 significantly inhibited SIRT1 enzyme activity, reduced the expression of SIRT1, increased cell cycle arrest at G 2 /M phase, and induced apoptotic cell death in SKOV3 cells via expression of cytochrome c, cleaved-PARP, cleaved caspase-3, and Bax. This might be associated with blocking of the pyruvate kinase M2 (PKM2)/mTOR pathway. MHY2245 also inhibited tumor growth and reduced tumor size when SKOV3 cells were transplanted into nude mice. Our results indicate that MHY2245 exerts antitumor activity against ovarian cancer cells by blocking the PKM2/mTOR pathway. We suggest that MHY2245 is a promising anticancer agent that disrupts ovarian cancer cell metabolism.

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Section: Mhy2245 Inhibits Human Ovarian Cell Tumors In Xenograft Modelsmentioning

confidence: 99%

A new SIRT1 inhibitor, MHY2245, induces autophagy and inhibits energy metabolism via PKM2/mTOR pathway in human ovarian cancer cells

Tae¹,

Son²,

Lee³

et al. 2020

Int. J. Biol. Sci.

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“…Surgery, radiation therapy, and chemotherapy are the most common treatments for cancer worldwide, but chemotherapy in particular has various side effects, including strong cytotoxicity caused by the drugs attacking normal cells [1][2][3]. Therefore, many researchers have looked to develop drug formulations that control the rate of release [4][5][6][7] in order to maintain constant concentrations of the drug in the blood or target organ [8].…”

Section: Introductionmentioning

confidence: 99%

NIR Laser-Responsive PNIPAM and Gold Nanorod Composites for the Engineering of Thermally Reactive Drug Delivery Nanomedicine

et al. 2020

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When ingesting a drug on its own or injecting it directly into tissue, its concentration increases immediately within the body, which often exacerbates the side effects and increases its toxicity. To solve this problem, we synthesized the thermally reactive polymer poly(N-isopropylacrylamide) (PNIPAM) using reversible addition–fragmentation chain transfer (RAFT) polymerization and prepared nanocarriers by binding PNIPAM to gold nanorods (GRs), with the anticancer agent doxorubicin (DOX) used as a model drug. PNIPAM changes from hydrophilic to hydrophobic at temperatures above its lower critical solution temperature, which represents a coil-to-globule volume phase transition. Because GRs absorb near-infrared (NIR) laser light and emit energy, PNIPAM aggregation occurs when the synthesized PNIPAM/GR are subjected to an NIR laser, and the temperature of the GRs rises. Using this principle, DOX was combined with the PNIPAM/GR complex, and the resulting anticancer effects with and without laser treatment were observed in Hela and MDA-MB-231 cells. In our proposed complex, the GR binding rate of PNIPAM reached 20% and the DOX binding rate reached 15%. The release profile of the drug following laser irradiation was determined using a drug release test and confocal microscopy imaging. It was subsequently confirmed that the release of the drug is higher at higher temperatures, especially with laser treatment. The proposed combination of temperature-reactive polymers and gold nanostructures shows promise for future research into controlled drug release.

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“…Regarding the first-line defense of chemo drugs in order to deal with the progression of several types of cancers, the incidence of chemoresistance is the main concern in cancer treatment protocols [109]. Besides the inherent chemoresistance form, the acquired types are demonstrated to result from the overactivation of some cellular signaling pathways or dysregulation of miRNAs or lncRNAs.…”

Section: Resultsmentioning

confidence: 99%

Signaling Pathways in Cervical Cancer Chemoresistance: Are microRNAs and Long-Noncoding RNAs the Main Culprits?

Mousavi¹,

Hemmat²,

Baghi³

et al. 2020

Preprint

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Cervical cancer is known as one of the most important cancers in women worldwide. Chemotherapy is a standard treatment for advanced/recurrent cervical cancer in which the prognosis of the disease is really poor and the 1-year survival chance in these patients is maximally 20%. However, resistance to anticancer drugs is a major problem in treating cancer. Cervical cancer stem cells are considered as a fundamental cause of chemo and radio-resistance and also relapse after primary successful treatment. Signaling pathways include a wide range of molecular mechanisms contribute to drug resistance. Recently, microRNAs (miRNAs) are announced as a group of molecular biomarkers involving in response to chemotherapy in cancer patients. As the miRNAs, there are some long non-coding RNAs (LncRNAs) which their aberrant expression is considered as a biomarker for monitoring chemoresistance. In this review, we summarized current reports about the involvement of signaling pathways during chemoresistance in cervical cancer. Then, genes that have been demonstrated their involvement during drug resistance in cervical cancer were tabulated. Further, miRNAs that have been reported as biomarkers during treatment are listed. By bioinformatic analysis, we predictedmiR-335-5p and miR-16-5p as the most potential biomarkers for monitoring resistance to chemotherapy. Finally, long non-coding RNAs that have been introduced in recent studies as novel biomarkers during the response to chemotherapy were mentioned.

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Chemoresistance of Cancer Cells: Requirements of Tumor Microenvironment-mimicking In Vitro Models in Anti-Cancer Drug Development

Cited by 150 publications

References 191 publications

A new SIRT1 inhibitor, MHY2245, induces autophagy and inhibits energy metabolism via PKM2/mTOR pathway in human ovarian cancer cells

A new SIRT1 inhibitor, MHY2245, induces autophagy and inhibits energy metabolism via PKM2/mTOR pathway in human ovarian cancer cells

NIR Laser-Responsive PNIPAM and Gold Nanorod Composites for the Engineering of Thermally Reactive Drug Delivery Nanomedicine

Signaling Pathways in Cervical Cancer Chemoresistance: Are microRNAs and Long-Noncoding RNAs the Main Culprits?

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