ABC-transporter blockage mediated by xanthotoxin and bergapten is the major pathway for chemosensitization of multidrug-resistant cancer cells

Mirzaei, Seyed Abbas; Dehkordi, Neda Gholamian; Ghamghami, Mahsa; Amiri, Amir; Abdolahinia, Elaheh Dalir; Elahian, Fatemeh

doi:10.1016/j.taap.2017.10.018

Cited by 34 publications

(27 citation statements)

References 41 publications

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“…Similarly, BCRP and MRP overexpression participates in MDR [111,112]. Bergapten and methoxsalen showed cytotoxicity in MDR1, MRP2 BCRP overexpressing gastric (EPG85.257RDB), ovarian (A2780RCIS) and breast (MCF7MX) cancer cell lines which showed reticence of MDR1, BCRP, and MRP efflux functions [113].…”

Section: Role In Mdr Cancersmentioning

confidence: 98%

“…Bergamottin, imperatorin, and isopimpinellin repressed CYP P450-1A1, -1A2, -3A4, and -1B1 (involve in carcinogen metabolism), in the MCF-7 cell lines [ 122 ]. MDR has been linked to BCRP, MRP, and MDR1 increase that expel cisplatin, daunorubicin, and mitoxantrone are very common in cancer therapeutics [ 113 ]. Bergapten and methoxsalen are capable of averting mitoxantrone, cisplatin, and daunorubicin binding to MDR1, BCRP, and MRP and, therefore, impeding their cellular efflux [ 113 ].…”

Section: Furanocoumarins As Adjuvant With Other Anticancer Agentsmentioning

confidence: 99%

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Anticancer Potential of Furanocoumarins: Mechanistic and Therapeutic Aspects

Ahmed

Khan

Aschner

et al. 2020

IJMS

133

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Cancer is one of the most extreme medical conditions in both developing and developed countries around the world, causing millions of deaths each year. Chemotherapy and/or radiotherapy are key for treatment approaches, but both have numerous adverse health effects. Furthermore, the resistance of cancerous cells to anticancer medication leads to treatment failure. The rising burden of cancer overall requires novel efficacious treatment modalities. Natural medications offer feasible alternative options against malignancy in contrast to western medication. Furanocoumarins’ defensive and restorative impacts have been observed in leukemia, glioma, breast, lung, renal, liver, colon, cervical, ovarian, and prostate malignancies. Experimental findings have shown that furanocoumarins activate multiple signaling pathways, leading to apoptosis, autophagy, antioxidant, antimetastatic, and cell cycle arrest in malignant cells. Additionally, furanocoumarins have been shown to have chemo preventive and chemotherapeutic synergistic potential when used in combination with other anticancer drugs. Here, we address different pathways which are activated by furanocoumarins and their therapeutic efficacy in various tumors. Ideally, this review will trigger interest in furanocoumarins and their potential efficacy and safety as a cancer lessening agents.

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Section: Role In Mdr Cancersmentioning

confidence: 98%

Section: Furanocoumarins As Adjuvant With Other Anticancer Agentsmentioning

confidence: 99%

Anticancer Potential of Furanocoumarins: Mechanistic and Therapeutic Aspects

Ahmed

Khan

Aschner

et al. 2020

IJMS

133

View full text Add to dashboard Cite

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“…Recent studies have reported that bergapten possesses various biological activities, including inhibition of ROS/NO generation to exhibit dual anti‐inflammatory and pro‐resolution activity, blockage of ABC transporter to promote chemosensitization of drug‐resistant cancer cells, regulation of phosphatidylinositide 3‐kinase (PI3K)/AKT, c‐Jun N‐terminal kinase (JNK), and nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB) signaling to inhibit diabetes‐related osteoporosis, and upregulation of PTEN to trigger autophagy . These findings indicate that bergapten is a potential therapeutic phytochemical that can not only potentially ameliorate inflammatory disorders but can also suppress the different types of carcinomas.…”

Section: Discussionmentioning

confidence: 99%

Bergapten induces G1 arrest and pro‐apoptotic cascade in colorectal cancer cells associating with p53/p21/PTEN axis

Lin

et al. 2018

Environmental Toxicology

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Bergapten is a natural compound and has potent anticancer activities. In this study, we explored the cytotoxicity of bergapten on colorectal cancer (CRC) cell DLD-1 and LoVo and its underlying mechanisms. We observed that bergapten (30 and 50 μM) decreased the viability of the CRC cells and induced the G0/G1 and sub-G1 phase arrest. Furthermore, immunoblotting results indicated that bergapten increased p53, phospho-p53(Ser-46), p21, PUMA, Bax, PTEN, and the caspase-9 and caspase-3 cleavage, but decreased cyclin E, CDK2, and phosphor-AKT(Ser-473) in the CRC cells. Inhibition of p53 by pifithrin-α reversed the bergapten-induced p53-mediated apoptotic cascade and restored the survival signaling and cell viability. Collectively, our findings reveal that bergapten decrease the cell viability and induce cell cycle arrest in the CRC cells, which may be attributed to p53-mediated apoptotic cascade, upregulation of p21 and PTEN, and inhibition of AKT. K E Y W O R D S apoptosis, colorectal cancer cells, Berga, PTEN, p21, p53

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“…10 5 events were recorded for samples and the following equations were used for the mathematical models where, MFI, modulator, sample and control are mean fluorescent intensity, pump inhibitors, shikonin treated cells and untreated cells, respectively. Appropriate negative controls were also included in the study and the experiments were repeated at least three independent times 42 , 44 . …”

Section: Methodsmentioning

confidence: 99%

Broad blocking of MDR efflux pumps by acetylshikonin and acetoxyisovalerylshikonin to generate hypersensitive phenotype of malignant carcinoma cells

Mirzaei

Reiisi

Tabari

et al. 2018

Sci Rep

Self Cite

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Cytotoxic activities of acetylshikonin and acetoxyisovalerylshikonin alone and in combination with chemotherapeutic agents against parental and drug resistant cell lines were determined using the MTT assay. Effects of Shikonin derivatives on BCRP, MDR1 and MRP transcript and protein levels were relatively measured. Finally, accumulation and efflux kinetics were conducted. The results revealed cell- and concentration-dependency of the cell cytotoxicity. Acetylshikonin and acetoxyisovalerylshikonin transiently made the mRNA ocean turbulent, but FACS analyses using fluorescent-labeled antibodies showed no significant change in the MDR-protein levels. Functional kinetics revealed significant block of MDR1, BCRP and MRP transporter in the presence of shikonin derivatives. Maximum accumulation fold changes was quantified to be 4.4 and consequently, acetoxyisovalerylshikonin pretreated EPG85.257RDB cells was chemosensitized to daunorubicin tension 3.1-fold. Although, the MDR blockage was reported to follow time- and cell-dependent patterns, MDR1, BCRP and MRP2 responses to the shikonins are concentration-independent. These data suggest uncompetitive transporter blockage behavior of these agents. The results indicated that shikonin derivatives stimulate uptake and reduce efflux of chemotherapeutic agents in the malignant cancer cells, suggesting that chemotherapy in combination with shikonin compounds may be beneficial to cancer cells that overexpress multidrug resistance transporters.

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ABC-transporter blockage mediated by xanthotoxin and bergapten is the major pathway for chemosensitization of multidrug-resistant cancer cells

Cited by 34 publications

References 41 publications

Anticancer Potential of Furanocoumarins: Mechanistic and Therapeutic Aspects

Anticancer Potential of Furanocoumarins: Mechanistic and Therapeutic Aspects

Bergapten induces G1 arrest and pro‐apoptotic cascade in colorectal cancer cells associating with p53/p21/PTEN axis

Broad blocking of MDR efflux pumps by acetylshikonin and acetoxyisovalerylshikonin to generate hypersensitive phenotype of malignant carcinoma cells

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