The Chinese herb polyphyllin D sensitizes ovarian cancer cells to cisplatin-induced growth arrest

Sawah, E. Al; Marchion, Douglas C.; Xiong, Yin; Ramírez, Ingrid; Abbasi, Forough; Boac, Bernadette M.; Bush, Stephen H.; Zgheib, Nadim Bou; McClung, C Robertson; Khulpateea, B.R.; Berry, Amy; Hakam, Ardeshir; Lancaster, Johnathan M.; Judson, Patricia L.

doi:10.1007/s00432-014-1797-x

Cited by 27 publications

(16 citation statements)

References 16 publications

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“…The natural compound PPI exhibits strong anti-cancer activity through targeting multiple signaling pathways and cancerassociated genes in different tumor types. 20,36,37) However, the molecular mechanisms underlying the anti-cancer activity of PPI, particularly toward EMT-associated acquired resistance remain unclear.…”

Section: Discussionmentioning

confidence: 99%

Polyphyllin I Overcomes EMT-Associated Resistance to Erlotinib in Lung Cancer Cells <i>via</i> IL-6/STAT3 Pathway Inhibition

Lou

Yan

Zhu

et al. 2017

Biological & Pharmaceutical Bulletin

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Acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) is the most important limiting factor for treatment efficiency in EGFR-mutant non-small cell lung cancer (NSCLC). Much work has linked the epithelial-mesenchymal transition (EMT) to the emergence of drug resistance, consequently, ongoing research has been focused on exploring the therapeutic options to reverse EMT for delaying or preventing drug resistance. Polyphyllin I (PPI) is a natural compound isolated from Paris polyphylla rhizomes and displayed anti-cancer properties. In the current work, we aimed to testify whether PPI could reverse EMT and overcome acquired EGFR-TKI resistance. We exposed HCC827 lung adenocarcinoma cells to erlotinib which resulted in acquired resistance with strong features of EMT. PPI effectively restored drug sensitivity of cells that obtained acquired resistance. PPI reversed EMT and decreased interleukin-6/signal transducer and activator of transcription 3 (IL-6/STAT3) signaling pathway activation in erlotinib-resistant cells. Moreover, addition of IL-6 partially abolished the sensitization response of PPI. Furthermore, co-treatment of erlotinib and PPI completed abrogation of tumor growth in xenografts, which was associated with EMT reversal. In conclusion, PPI serves as a novel solution to conquer the EGFR-TKI resistance of NSCLC via reversing EMT by modulating IL-6/STAT3 signaling pathway. Combined PPI and erlotinib treatment provides a promising future for lung cancer patients to strengthen drug response and prolong survival.

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Section: Discussionmentioning

confidence: 99%

Polyphyllin I Overcomes EMT-Associated Resistance to Erlotinib in Lung Cancer Cells <i>via</i> IL-6/STAT3 Pathway Inhibition

Lou

Yan

Zhu

et al. 2017

Biological & Pharmaceutical Bulletin

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“…Polyphyllin I (PPI) and polyphyllin VII (PPVII) are two of the primary active components isolated from RPS, which exhibit strong anticancer effects in a number of different types of cancer by regulating the signaling pathways associated with proliferation, apoptosis and autophagy (19)(20)(21)(22)(23)(24)(25)(26)(27). Notably, PPI and PPVII have also been demonstrated to possess chemosensitizing effects in a number of different types of cancer (28)(29)(30)(31)(32). However, the effects of PPI and PPVII on DDP-resistant lung cancer cells remain unclear.…”

Section: Introductionmentioning

confidence: 99%

Polyphyllin I and VII potentiate the chemosensitivity of A549/DDP cells to cisplatin by enhancing apoptosis, reversing EMT and suppressing the CIP2A/AKT/mTOR signaling axis

et al. 2019

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Poor response and resistance to cisplatin (DDP)-based chemotherapy frequently leads to treatment failure in advanced non-small cell lung cancer (NSCLC). The underlying molecular mechanism is extremely complex and currently remains unclear. The overexpression of cancerous inhibitor of protein phosphatase 2A (CIP2A) indicates poor prognosis and promotes the epithelial-to-mesenchymal transition (EMT) and metastasis. The EMT has been reported to promote drug resistance in numerous previous studies. CIP2A and its downstream protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway also plays a role in mediating DDP resistance. Polyphyllin I (PPI) and polyphyllin VII (PPVII) are natural components extracted from Paris polyphylla that display anti-cancer properties. In the present study, the chemosensitizing effects of PPI and PPVII were investigated in the DDP-resistant NSCLC cell line A549/DDP, as well as the underlying molecular mechanisms. The results demonstrated that PPI and PPVII could significantly inhibit cell proliferation and enhance the sensitivities of A549/DDP cells to DDP. When assessing the underlying molecular mechanism, it was revealed that PPI and PPVII enhanced DDP-induced apoptosis in A549/DDP cells via p53 upregulation and the caspase-dependent pathway. Furthermore, PPI and PPVII reversed the EMT and suppressed CIP2A and its downstream AKT/mTOR signaling cascade in A549/DDP cells. Overall, the results from the present study demonstrated that PPI and PPVII may function as chemosensitizers by enhancing apoptosis via the p53 pathway, reversing EMT and suppressing the CIP2A/AKT/mTOR signaling axis, and the combination with DDP may be a promising strategy for the development of new therapeutic agents.

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“…Chonglou is a popular TCM. It showed diverse bioactivities such as hemostatic [5,6], anti-inflammatory [7], anti-fibrotic [8] and anticancer activities [9,10]. The steroid saponins are the major Correspondence: Dr. Shuang-cheng Ma, National Institutes for Food and Drug Control, No.…”

Section: Introductionmentioning

confidence: 99%

Multi‐component determination and chemometric analysis of Paris polyphylla by ultra high performance liquid chromatography with photodiode array detection

Chen

Jin

Sun

et al. 2016

J of Separation Science

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Multi-source analysis of traditional Chinese medicine is key to ensuring its safety and efficacy. Compared with traditional experimental differentiation, chemometric analysis is a simpler strategy to identify traditional Chinese medicines. Multi-component analysis plays an increasingly vital role in the quality control of traditional Chinese medicines. A novel strategy, based on chemometric analysis and quantitative analysis of multiple components, was proposed to easily and effectively control the quality of traditional Chinese medicines such as Chonglou. Ultra high performance liquid chromatography was more convenient and efficient. Five species of Chonglou were distinguished by chemometric analysis and nine saponins, including Chonglou saponins I, II, V, VI, VII, D, and H, as well as dioscin and gracillin, were determined in 18 min. The method is feasible and credible, and enables to improve quality control of traditional Chinese medicines and natural products.

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The Chinese herb polyphyllin D sensitizes ovarian cancer cells to cisplatin-induced growth arrest

Abstract: Our findings highlight the value of PD as a natural product with anti-cancer properties, which may also enhance the activity of existing therapeutic agents.

Cited by 27 publications

References 16 publications

Polyphyllin I Overcomes EMT-Associated Resistance to Erlotinib in Lung Cancer Cells <i>via</i> IL-6/STAT3 Pathway Inhibition

Polyphyllin I Overcomes EMT-Associated Resistance to Erlotinib in Lung Cancer Cells <i>via</i> IL-6/STAT3 Pathway Inhibition

Polyphyllin I and VII potentiate the chemosensitivity of A549/DDP cells to cisplatin by enhancing apoptosis, reversing EMT and suppressing the CIP2A/AKT/mTOR signaling axis

Multi‐component determination and chemometric analysis of Paris polyphylla by ultra high performance liquid chromatography with photodiode array detection

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