Role of membrane-embedded drug efflux ABC transporters in the cancer chemotherapy

Gupta, Sonu Kumar; Singh, Priyanka; Ali, Villayat; Verma, Malkhey

doi:10.4081/oncol.2020.448

Cited by 45 publications

(36 citation statements)

References 127 publications

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“…Increasing evidence illustrates that miRNAs are implicated in the expansion and development of MDR in tumour cells by modulating the expression of different protein translation targets (Lee et al., 2020; Zhu et al., 2020). Hence, the comprehensive understanding of the mechanism of miRNAs regulation may contribute to the improvement of MDR‐reversing agents (Gupta et al., 2020). Lu et al.…”

Section: Discussionmentioning

confidence: 99%

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miR‐21 inhibition reverses doxorubicin‐resistance and inhibits PC3 human prostate cancer cells proliferation

Zhao

Ning²,

Wang

et al. 2021

Andrologia

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Many approaches have been examined to reversing multidrug resistance (MDR), but sub‐optimal target‐based strategies have limited their efficacy. Herein, we investigate microRNA (miR‐21) suppression on the doxorubicin (DOX)‐sensitisation of the DOX‐resistant (PC3/DOX) cell line in prostate cancer (PCa). Expression levels of miR‐21, P‐glycoprotein (P‐gp), MDR‐1 and PTEN evaluated in PC3/DOX cancer cells by qRT‐PCR and western blot analyses. The cytotoxic effects of transfected of miR‐21 were assessed by MTT assay for 72 hr. Rhodamine123 (Rh123) assay was employed to define the activity of P‐gp. Apoptosis was detected by Flow cytometry. As expected, miR‐21 was expressed highly in PC3/DOX cells (p < 0.05). It was shown that miRNA‑21 suppression considerably hindered PC3/DOX cell viability. miR‑21 suppression dramatically downregulated P‐gp expression and activity in DOX‐resistance cells and abolished MDR by an increment of intracellular accumulation of DOX in PC3/DOX cells (p < 0.05). PTEN is a key modulator of the PI3K/Akt/P‐gp cascade, which miR‐21 suppression led to the upregulation of PTEN and sequentially lower‐expression of P‐gp that reversed MDR. Also, miR‐21 repression enhanced the apoptosis rate of PC3/DOX cells. The findings of this paper contribute to the current understanding of the functions of miR‐21 in MDR‐reversing in PCa.

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Section: Discussionmentioning

confidence: 99%

“…Zhu et al, 2020). Hence, the comprehensive understanding of the mechanism of miRNAs regulation may contribute to the improvement of MDR-reversing agents (Gupta et al, 2020). revealed that miR-21 is overexpressed in 15 malignancy kinds, which alleviated the overall survival in 6 types of carcinoma cases.…”

Section: Discussionmentioning

confidence: 99%

miR‐21 inhibition reverses doxorubicin‐resistance and inhibits PC3 human prostate cancer cells proliferation

Zhao

Ning²,

Wang

et al. 2021

Andrologia

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“…colchicine, and the vinca alkaloids vinblastine and vincristine inhibit polymerisation of microtubules 17 . Significant attention is now focussed on colchicine binding site inhibitors due to their positive impact on ABC-transporter-mediated drug resistance 18,19 . Combretastatin A-4 (CA-4), (1, Figure 1) has been reported as the most potent antimitotic agent of this family against several tumour cells 20 .…”

Section: Introductionmentioning

confidence: 99%

Discovery of novel quinoline-based analogues of combretastatin A-4 as tubulin polymerisation inhibitors with apoptosis inducing activity and potent anticancer effect

Ibrahim

Hawwas

Malebari

et al. 2021

Journal of Enzyme Inhibition and Medicinal Chemistry

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A new series of quinoline derivatives of combretastatin A-4 have been designed, synthesised and demonstrated as tubulin polymerisation inhibitors. These novel compounds showed significant antiproliferative activities, among them, 12c exhibited the most potent inhibitory activity against different cancer cell lines (MCF-7, HL-60, HCT-116 and HeLa) with IC 50 ranging from 0.010 to 0.042 mM, and with selectivity profile against MCF-10A non-cancer cells. Further mechanistic studies suggest that 12c can inhibit tubulin polymerisation and cell migration, leading to G 2 /M phase arrest. Besides, 12c induces apoptosis via a mitochondrial-dependant apoptosis pathway and caused reactive oxygen stress generation in MCF-7 cells. These results provide guidance for further rational development of potent tubulin polymerisation inhibitors for the treatment of cancer. HIGHLIGHTS A novel series of quinoline derivatives of combretastatin A-4 have been designed and synthesised. Compound 12c showed significant antiproliferative activities against different cancer cell lines. Compound 12c effectively inhibited tubulin polymerisation and competed with [ 3 H] colchicine in binding to tubulin. Compound 12c arrested the cell cycle at G 2 /M phase, effectively inducing apoptosis and inhibition of cell migration.

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“…In Table 1 , some of the well-known lncRNAs involved in the event of cancer drug resistance have been summarized. The principal mechanisms of drug resistance in cancer cells are: (1) overexpression of drug efflux transporters like ATP-binding cassette (ABC) superfamily pumps [ 97 ]; (2) enhanced repair of chemotherapy induced-genome damages [ 98 ]; (3) alternation signaling pathways controlling drug resistance [ 99 ]; (4) enhanced modulation of drug metabolism; (5) increasing resistance to cell death mechanisms [ 100 ]; and (6) EMT [ 99 ].…”

Section: Role Of Lncrnas In Human Cancersmentioning

confidence: 99%

Regulation of Long Non-Coding RNAs by Plant Secondary Metabolites: A Novel Anticancer Therapeutic Approach

Kalhori

Khodayari

et al. 2021

Cancers

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Long non-coding RNAs (lncRNAs) are a class of non-coding RNAs that play an essential role in various cellular activities, such as differentiation, proliferation, and apoptosis. Dysregulation of lncRNAs serves a fundamental role in the progression and initiation of various diseases, including cancer. Precision medicine is a suitable and optimal treatment method for cancer so that based on each patient’s genetic content, a specific treatment or drug is prescribed. The rapid advancement of science and technology in recent years has led to many successes in this particular treatment. Phytochemicals are a group of natural compounds extracted from fruits, vegetables, and plants. Through the downregulation of oncogenic lncRNAs or upregulation of tumor suppressor lncRNAs, these bioactive compounds can inhibit metastasis, proliferation, invasion, migration, and cancer cells. These natural products can be a novel and alternative strategy for cancer treatment and improve tumor cells’ sensitivity to standard adjuvant therapies. This review will discuss the antineoplastic effects of bioactive plant secondary metabolites (phytochemicals) via regulation of expression of lncRNAs in various human cancers and their potential for the treatment and prevention of human cancers.

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Role of membrane-embedded drug efflux ABC transporters in the cancer chemotherapy

Cited by 45 publications

References 127 publications

miR‐21 inhibition reverses doxorubicin‐resistance and inhibits PC3 human prostate cancer cells proliferation

miR‐21 inhibition reverses doxorubicin‐resistance and inhibits PC3 human prostate cancer cells proliferation

Discovery of novel quinoline-based analogues of combretastatin A-4 as tubulin polymerisation inhibitors with apoptosis inducing activity and potent anticancer effect

Regulation of Long Non-Coding RNAs by Plant Secondary Metabolites: A Novel Anticancer Therapeutic Approach

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