Cancer multidrug-resistance reversal by ABCB1 inhibition: A recent update

Engle, Kritika; Kumar, Gaurav

doi:10.1016/j.ejmech.2022.114542

Cited by 89 publications

(67 citation statements)

References 152 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…ABC transporter depends on the hydrolysis of ATP, and low ATP concentration has the strong ability to inhibit the ABC transporters [ 34 ]. The inhibition of mTOR also increases the drug sensitivity of cancer cells [ 35 ]. Therefore, targeting AMPK/mTOR can effectively inhibit tumor formation and enhance chemotherapeutic sensitivity, and disruption of ATP level may be a more straightforward strategy to overcome drug resistance [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

Modulating p-AMPK/mTOR Pathway of Mitochondrial Dysfunction Caused by MTERF1 Abnormal Expression in Colorectal Cancer Cells

Liu

Zhang

Zou

et al. 2022

IJMS

View full text Add to dashboard Cite

Human mitochondrial transcription termination factor 1 (MTERF1) has been demonstrated to play an important role in mitochondrial gene expression regulation. However, the molecular mechanism of MTERF1 in colorectal cancer (CRC) remains largely unknown. Here, we found that MTERF1 expression was significantly increased in colon cancer tissues compared with normal colorectal tissue by Western blotting, immunohistochemistry, and tissue microarrays (TMA). Overexpression of MTERF1 in the HT29 cell promoted cell proliferation, migration, invasion, and xenograft tumor formation, whereas knockdown of MTERF1 in HCT116 cells appeared to be the opposite phenotype to HT29 cells. Furthermore, MTERF1 can increase mitochondrial DNA (mtDNA) replication, transcription, and protein synthesis in colorectal cancer cells; increase ATP levels, the mitochondrial crista density, mitochondrial membrane potential, and oxygen consumption rate (OCR); and reduce the ROS production in colorectal cancer cells, thereby enhancing mitochondrial oxidative phosphorylation (OXPHOS) activity. Mechanistically, we revealed that MTERF1 regulates the AMPK/mTOR signaling pathway in cancerous cell lines, and we also confirmed the involvement of the AMPK/mTOR signaling pathway in both xenograft tumor tissues and colorectal cancer tissues. In summary, our data reveal an oncogenic role of MTERF1 in CRC progression, indicating that MTERF1 may represent a new therapeutic target in the future.

show abstract

Section: Discussionmentioning

confidence: 99%

Modulating p-AMPK/mTOR Pathway of Mitochondrial Dysfunction Caused by MTERF1 Abnormal Expression in Colorectal Cancer Cells

Liu

Zhang

Zou

et al. 2022

IJMS

View full text Add to dashboard Cite

show abstract

“…The changes cancer cells underwent during OXA tolerance need to be explored in the future. Though studies on ABC transporters are increasing, the limitations and side effects of several generations of inhibitors make their clinical application difficult ( Mohammad et al., 2020 ; Robey et al., 2018 ; Engle & Kumar, 2022 ). Due to the inhibition of ABC transporters, reversal of resistance to OXA, and safe side effects of GQD, developing new transporter inhibitors is possible.…”

Section: Discussionmentioning

confidence: 99%

The potential effects and mechanisms of Gegen Qinlian Decoction in oxaliplatin-resistant colorectal cancer based on network pharmacology

Lin¹,

Xu²,

Tan

et al. 2022

Heliyon

View full text Add to dashboard Cite

“…Besides the lack of adequate therapies and late discovery in many cases, the development of multidrug resistance (MDR) contributes to this high mortality. One important mechanism by which cancer cells resist cytotoxic drugs is increasing the expression of specific efflux pumps that shuttle organic molecules to the outside of the cell across the plasma membrane, preventing their intracellular accumulation to cytotoxic levels and ultimately leading to therapeutic failure [ 2 , 3 ]. These transmembrane efflux pumps include P-glycoprotein (P-gp), a member of the ATP-binding cassette (ABC) family of transporters that are associated with cancer drug resistance [ 4 , 5 ].…”

Section: Introductionmentioning

confidence: 99%

“…These transmembrane efflux pumps include P-glycoprotein (P-gp), a member of the ATP-binding cassette (ABC) family of transporters that are associated with cancer drug resistance [ 4 , 5 ]. Thus, targeting these transporters would increase treatment efficacy and decrease cancer-associated mortality [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

“…The activity of the ABC family of transporters protects normal body cells from chemical insults by shuttling xenobiotic molecules across the cell membrane [ 6 ]. Contrarily, the expression and function of such transport systems largely determine the susceptibility of cancer cells to chemotherapeutic agents [ 2 , 3 ]. The increased expression and/or activity of P-gp, encoded in humans by the ABCB1 gene, confers resistance to anticancer drugs [ 4 , 5 ].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Carnosine Potentiates Doxorubicin-Induced Cytotoxicity in Resistant NCI/ADR-RES Cells by Inhibiting P-Glycoprotein—In Silico and In Vitro Evidence

Morsy

Kandeel²,

Ibrahim³

et al. 2022

Molecules

View full text Add to dashboard Cite

The activity of the P-glycoprotein (P-gp) transporter encoded by the ABCB1 gene confers resistance to anticancer drugs and contributes to cancer-related mortality and morbidity. Recent studies revealed the cytotoxic effects of the endogenous dipeptide carnosine. The current study aimed to investigate the role of carnosine as a potential inhibitor of P-gp activity. We used molecular docking and molecular dynamic simulations to study the possible binding and stability of carnosine-P-gp interactions compared with verapamil. In vitro assays using doxorubicin-resistant NCI/ADR-RES cells were established to test the effects of carnosine (10–300 µM) on P-gp activity by the rhodamine-123 efflux assay and its effect on cell viability and doxorubicin-induced cytotoxicity. Verapamil (10 µM) was used as a positive control. The results showed that carnosine binding depends mainly on hydrogen bonding with GLU875, GLN946, and ALA871, with a higher average Hbond than verapamil. Carnosine showed significant but weaker than verapamil-induced rhodamine-123 accumulation. Carnosine and verapamil similarly inhibited cell viability. However, verapamil showed a more significant potentiating effect on doxorubicin-induced cytotoxicity than a weaker effect of carnosine at 300 µM. These results suggest that carnosine inhibits P-gp activity and potentiates doxorubicin-induced cytotoxicity at higher concentrations. Carnosine might be a helpful lead compound in the fight against multidrug-resistant cancers.

show abstract

Cancer multidrug-resistance reversal by ABCB1 inhibition: A recent update

Cited by 89 publications

References 152 publications

Modulating p-AMPK/mTOR Pathway of Mitochondrial Dysfunction Caused by MTERF1 Abnormal Expression in Colorectal Cancer Cells

Modulating p-AMPK/mTOR Pathway of Mitochondrial Dysfunction Caused by MTERF1 Abnormal Expression in Colorectal Cancer Cells

The potential effects and mechanisms of Gegen Qinlian Decoction in oxaliplatin-resistant colorectal cancer based on network pharmacology

Carnosine Potentiates Doxorubicin-Induced Cytotoxicity in Resistant NCI/ADR-RES Cells by Inhibiting P-Glycoprotein—In Silico and In Vitro Evidence

Contact Info

Product

Resources

About