Tomentodione M sensitizes multidrug resistant cancer cells by decreasing P-glycoprotein via inhibition of p38 MAPK signaling

Zhou, Xu-Wei; Xia, Yuan‐Zheng; Zhang, Yalong; Luo, Jian‐Guang; Han, Chao; Zhang, Hao; Zhang, Chao; Yang, Lei; Kong, Ling–Yi

doi:10.18632/oncotarget.21949

Cited by 23 publications

(18 citation statements)

References 73 publications

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“…Recently, Zhou and colleagues have found that tomentodione M, a novel meroterpenoid isolated from R. tomentosa leaves, increased the cytotoxicity of chemotherapeutic drugs such as docetaxel and doxorubicin in human breast cancer cells/reversed multidrug resistance (MCF-7/MDR cells) and human immortalized myelogenous leukemia cells/reversed multidrug resistance (K562/MDR cells). Additionally, the anticancer activity of tomentodione M was observed due to reducing colony formation, enhancing apoptosis in docetaxel-treated MCF-7/MDR and K562/MDR cells, increasing intracellular accumulation of doxorubicin and rhodamine 123 in MDR cancer cells, and down-regulating P-gp mRNA and protein expression [96]. Thus, tomentodione M may be a useful anticancer natural product.…”

Section: Pharmaceutical Propertiesmentioning

confidence: 99%

The Health Beneficial Properties of Rhodomyrtus tomentosa as Potential Functional Food

Ngo

2019

Biomolecules

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Rhodomyrtus tomentosa (Aiton) Hassk. is a flowering plant belonging to the family Myrtaceae, native to southern and southeastern Asia. It has been used in traditional Vietnamese, Chinese, and Malaysian medicine for a long time for the treatment of diarrhea, dysentery, gynecopathy, stomachache, and wound healing. Moreover, R. tomentosa is used to make various food products such as wine, tea, and jam. Notably, R. tomentosa has been known to contain structurally diverse and biologically active metabolites, thus serving as a potential resource for exploring novel functional agents. Up to now, numerous phenolic and terpenoid compounds from the leaves, root, or fruits of R. tomentosa have been identified, and their biological activities such as antioxidant, antibacterial, anti-inflammatory, and anticancer have been evidenced. In this contribution, an overview of R. tomentosa and its health beneficial properties was focused on and emphasized.

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Section: Pharmaceutical Propertiesmentioning

confidence: 99%

The Health Beneficial Properties of Rhodomyrtus tomentosa as Potential Functional Food

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2019

Biomolecules

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“…Novel pharmacological approaches to overcome drug resistance in cancer have been established in recent decades. Targeting active drug transporters such as MDR1, for example, can resensitize drug-resistant tumor cells to anti-cancer drugs [7,8].…”

Section: Introductionmentioning

confidence: 99%

Cordycepin Resensitizes T24R2 Cisplatin-Resistant Human Bladder Cancer Cells to Cisplatin by Inactivating Ets-1 Dependent MDR1 Transcription

Lee

Madhi

et al. 2020

IJMS

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Tumor cell resistance to anti-cancer drugs is a major obstacle in tumor therapy. In this study, we investigated the mechanism of cordycepin-mediated resensitization to cisplatin in T24R2 cells, a T24-derived cell line. Treatment with cordycepin or cisplatin (2 μg/mL) alone failed to induce cell death in T24R2 cells, but combination treatment with these drugs significantly induced apoptosis through mitochondrial pathways, including depolarization of mitochondrial membranes, decrease in anti-apoptotic proteins Bcl-2, Bcl-xL, and Mcl-1, and increase in pro-apoptotic proteins Bak and Bax. High expression levels of MDR1 were the cause of cisplatin resistance in T24R2 cells, and cordycepin significantly reduced MDR1 expression through inhibition of MDR1 promoter activity. MDR1 promoter activity was dependent on transcription factor Ets-1 in T24R2 cells. Although correlation exists between MDR1 and Ets-1 expression in bladder cancer patients, active Ets-1, Thr38 phosphorylated form (pThr38), was critical to induce MDR1 expression. Cordycepin decreased pThr-38 Ets-1 levels and reduced MDR1 transcription, probably through its effects on PI3K signaling, inducing the resensitization of T24R2 cells to cisplatin. The results suggest that cordycepin effectively resensitizes cisplatin-resistant bladder cancer cells to cisplatin, thus serving as a potential strategy for treatment of cancer in patients with resistance to anti-cancer drugs.

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“…6) ABCB1 is a target of the Ras/Raf signaling pathway, suppression of p38, ERK or JNK pathways enhanced sensitivity to chemotherapeutic drugs in multidrug resistant tumor cells. [7][8][9][10] Paris polyphylla var. yunnanensis (Franch.)…”

Section: Introductionmentioning

confidence: 99%

Total Saponins from <i>Paris forrestii</i> Reverse Multidrug Resistance of MCF-7/ADM Cells by Suppression of P-gp <i>via</i> ERK Signaling Pathway

Chai

Yuan

Zhu

et al. 2020

Biological & Pharmaceutical Bulletin

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Our previous study demonstrated that the total saponins from Paris forristii (PCT3)had obvious inhibitory effect on the proliferation of adriamycin-resistant human breast adenocarcinoma cells (MCF-7/ADM), this effect was significantly stronger than that in parental cells (MCF-7). This study was designed to test the reversal effect of PCT3 on MCF-7/ADM cells and to understand its mechanism of action. Results demonstrated that low cytotoxic concentrations of PCT3 (0.3, 1 and 3 µg/ml) reversed resistance of MCF-7/ADM cells to ADM, DDP and 5-FU, with reversal fold of 16.4, 19.5 and 31.7 for ADM, 1.6, 1.4 and 1.4 for DDP, 1.7, 1.8 and 5.6 for 5-FU, respectively. Moreover, PCT3 significantly increased the accumulation of ADM and Rh123 in MCF-7/ADM cells, suggesting that PCT3 may act by affecting the function of drug efflux pump P-gp, which is encoded by MDR1 gene. Both MDR1 gene and P-gp protein expression was downregulated by PCT3 treatment. Further results demonstrated that p38MAPK and ERK pathway was remarkably activated in MCF-7/ADM cells, inhibition of p38 or ERK attenuated P-gp expression. While, only the phosphorylation level of ERK was downregulated by PCT3, indicating that PCT3 sensitized P-gp overexpressed MCF-7/ADM cells to ADM via inhibition of ERK signaling pathway.

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Tomentodione M sensitizes multidrug resistant cancer cells by decreasing P-glycoprotein via inhibition of p38 MAPK signaling

Cited by 23 publications

References 73 publications

The Health Beneficial Properties of Rhodomyrtus tomentosa as Potential Functional Food

The Health Beneficial Properties of Rhodomyrtus tomentosa as Potential Functional Food

Cordycepin Resensitizes T24R2 Cisplatin-Resistant Human Bladder Cancer Cells to Cisplatin by Inactivating Ets-1 Dependent MDR1 Transcription

Total Saponins from <i>Paris forrestii</i> Reverse Multidrug Resistance of MCF-7/ADM Cells by Suppression of P-gp <i>via</i> ERK Signaling Pathway

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