Cisplatin prevents breast cancer metastasis through blocking early EMT and retards cancer growth together with paclitaxel

Wang, Haitao; Guo, Sen; Kim, Seung Jin; Shao, Fangyuan; Ho, Joshua W. K.; Wong, Kuan Un; Miao, Zhengqiang; Hao, Dapeng; Zhao, Ming; Xu, Jun; Zeng, Jianming; Wong, Koon Ho; Di, Lijun; Wong, Ada Hang Heng; Xu, Xiaoling; Deng, Chu Xia

doi:10.7150/thno.46460

Cited by 85 publications

(52 citation statements)

References 86 publications

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“…However, a much more important problem associated with cytostatic treatment is the phenomenon of multidrug resistance (MDR). It turns out that despite a good initial response to cisPt application in BC patients, resistance to this drug develops over time and thus negatively affects its therapeutic efficacy [ 4 , 5 ]. Resistance to cisPt develops at multiple levels of the neoplastic cell and its environment.…”

Section: Introductionmentioning

confidence: 99%

Mechanism of Anticancer Action of Novel Imidazole Platinum(II) Complex Conjugated with G2 PAMAM-OH Dendrimer in Breast Cancer Cells

Czarnomysy

Muszyńska

Rok

et al. 2021

IJMS

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Transition metal coordination compounds play an important role in the treatment of neoplastic diseases. However, due to their low selectivity and bioavailability, as well as the frequently occurring phenomenon of drug resistance, new chemical compounds that could overcome these phenomena are still being sought. The solution seems to be the synthesis of new metal complexes conjugated with drug carriers, e.g., dendrimers. Numerous literature data have shown that dendrimers improve the bioavailability of the obtained metal complexes, solving the problem of their poor solubility and stability in an aqueous environment and also breaking down inborn and acquired drug resistance. Therefore, the aim of this study was to synthesize a novel imidazole platinum(II) complex conjugated with and without the second-generation PAMAM dendrimer (PtMet2–PAMAM and PtMet2, respectively) and to evaluate its antitumor activity. Cell viability studies indicated that PtMet2–PAMAM exhibited higher cytotoxic activity than PtMet2 in MCF-7 and MDA-MB-231 breast cancer cells at relatively low concentrations. Moreover, our results indicated that PtMet2–PAMAM exerted antiproliferative effects in a zebrafish embryo model. Treatment with PtMet2–PAMAM substantially increased apoptosis in a dose-dependent manner via caspase-9 (intrinsic pathway) and caspase-8 (extrinsic pathway) activation along with pro-apoptotic protein expression modulation. Additionally, we showed that apoptosis can be induced by activating POX, which induces ROS production. Furthermore, our results also clearly showed that the tested compounds trigger autophagy through p38 pathway activation and increase Beclin-1, LC3, AMPK, and mTOR inhibition. The high pro-apoptotic activity and the ability to activate autophagy by the imidazole platinum(II) complex conjugated with a dendrimer may be due to its demonstrated ability to reverse multidrug resistance (MDR) and thereby increase cellular accumulation in breast cancer cells.

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Section: Introductionmentioning

confidence: 99%

Mechanism of Anticancer Action of Novel Imidazole Platinum(II) Complex Conjugated with G2 PAMAM-OH Dendrimer in Breast Cancer Cells

Czarnomysy

Muszyńska

Rok

et al. 2021

IJMS

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“…Thus, most of colon cancer patients treated with CDDP are destined to experience therapeutic failure and tumor recurrence [7]. Recently, combined chemotherapy involving CDDP has been proved to be a better treatment strategy compared with single-agent therapy [8][9][10]. Therefore, it is urgently needed to search for effective agents that are capable of enhancing the therapeutic effect of CDDP and minimizing its side effects.…”

Section: Introductionmentioning

confidence: 99%

Synergistic Antitumor Effect of Andrographolide and Cisplatin Through ROS-Mediated ER Stress and STAT3 Inhibition in Colon Cancer

Huang

Cao

Wang

et al. 2021

Preprint

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Colon cancer is one of the most leading death-causing cancers in the world. Cisplatin has been widely used as the first-line treatment of cancer. However, its clinical application is limited by the side effects or acquired drug resistance. Hence, it is of vital clinical significance to develop novel agents that synergize with cisplatin and decrease its side effects. The aim of this study was to investigate whether Andrographolide (AP) synergistically potentiates the anti-tumor effect of cisplatin on colon cancer cells. Here, we found that AP synergizes with cisplatin in exerting anticancer activity in colon cancer cells. Further studies showed that AP potentiates cisplatin-induced endoplasmic reticulum stress and STAT3 inhibition through increasing intracellular ROS. Notably, pre-treatment of NAC, a ROS scavenger, reversed apoptosis induced by combined treatment of AP and cisplatin, while relieving the activation of endoplasmic reticulum stress as well as STAT3 inhibition. These findings indicated that ROS plays a pivotal role in mediating synergistic anticancer effects of AP and cisplatin on colon cancer cells. Overall, this study presents a potential new therapeutic strategy for the treatment of colon cancer.

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“…Cisplatin blocks the cell migration induced by transforming growth factor-beta (TGF- β ), which acts as a tumor promoter that leads to metastasis. On MDA-MB-231 cells, cisplatin blocks the filopodia formation associated with dynamic cytoskeleton rearrangement induced by TGF- β cells during cell movement [ 20 ]. The fraction F provides similar activity to control, which is cisplatin observed 12 hr after treatment.…”

Section: Resultsmentioning

confidence: 99%

Cytotoxic and Antimigration Activity of Etlingera alba (A.D.) Poulsen Rhizome

Wahyuni

Diantini

Ghozali

et al. 2021

Advances in Pharmacological and Pharmaceutical Sciences

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Etlingera alba is one of the Etlingera plants that might have anticancer activity. This study aims to investigate the cytotoxic and antimetastatic activity of E. alba rhizome fractions and migration cell assay against MDA-MB-231 cell lines, which are used for triple-negative breast cancer (TNBC) treatment assay. The cytotoxic activity was assayed using CCK-8 assay, while the antimetastatic was assayed using migration cell assay for the fractions A–F. They were followed by LCMS/MS profiling to determine the chemical contents in the most active fraction. According to results obtained, fraction B was the most active fraction for cytotoxic activity with an IC50 value of 65.43 μg/mL, while fraction E was the most active fraction for antimetastasis activity against migration rate doses of 50, 100, and 200 ppm which were 6.80, 3.66, and 3.00%, respectively. Several compounds in fraction B, such as rengyolone, licochalcone A, sugiol, and spinasterol, might have been known to have activity against cancer cells, as well as aschantin and lirioresinol B dimethyl ether from fraction E. In conclusion, the chemical components from E. alba rhizome fractions provided potency for discovering new agents for cancer treatment, specifically for TNBC.

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Cisplatin prevents breast cancer metastasis through blocking early EMT and retards cancer growth together with paclitaxel

Cited by 85 publications

References 86 publications

Mechanism of Anticancer Action of Novel Imidazole Platinum(II) Complex Conjugated with G2 PAMAM-OH Dendrimer in Breast Cancer Cells

Mechanism of Anticancer Action of Novel Imidazole Platinum(II) Complex Conjugated with G2 PAMAM-OH Dendrimer in Breast Cancer Cells

Synergistic Antitumor Effect of Andrographolide and Cisplatin Through ROS-Mediated ER Stress and STAT3 Inhibition in Colon Cancer

Cytotoxic and Antimigration Activity of Etlingera alba (A.D.) Poulsen Rhizome

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