Phyto-sesquiterpene lactone deoxyelephantopin and cisplatin synergistically suppress lung metastasis of B16 melanoma in mice with reduced nephrotoxicity

Chao, Wen-Wan; Cheng, Ya‐Wen; Chen, Yet-Ran; Lee, Shu-Hua; Chiou, Ching-Yi; Shyur, Lie‐Fen

doi:10.1016/j.phymed.2018.11.005

Cited by 21 publications

(19 citation statements)

References 32 publications

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“…The combination of anti-tumor agents should be able to produce synergistic or additive therapeutic e cacies, reduced side effects and minimal drug resistance. Experimental strategies that investigate combinational therapy of CDDP with natural plant extracts/plant-derived agents to maintain the desired antitumor e cacy have been reported [9,36,37]. In this study, HWG in combined with CDDP inhibits the invasion of these RCC cells, especially at a concentration of more than 100 mg/mL and inhibited the wound-healing migration of these RCC cells, especially at a concentration of more than 200 mg/mL.…”

Section: Discussionmentioning

confidence: 76%

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Bidirect effects from cisplatin combine with rosmarinic acid (RA) or hot water extracts of Glechoma hederacea (HWG) on renal cancer cells

Chou

Tai

et al. 2020

Preprint

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Abstract Background: Cisplatin (CDDP) is a chemotherapeutic drug which also causes adverse side effects. Glechoma hederacea is a traditional Chinese herb belonging to the Labiatae family and has many biological activities. Our previous study indicated that rosmarinic acid (RA) was the most abundant phytochemical in G. hederacea. However, the antioxidant or anti-inflammatory effects of the combined treatment of G. hederacea, RA and CDDP on human renal cell carcinoma (RCC) 786-O cells have not been clearly demonstrated. We aimed to investigate the bioefficacy of hot water extracts of G. hederacea (HWG) and RA in inhibiting RCC 786-O cell activity and its synergism with CDDP against metastatic renal cancer cell. Methods: Bioactivities of the combination treatment of HWG, RA, HWG/CDDP and RA/CDDP were assessed using the MTT assay and transwell migration, and the crude extract/compound efficacy was evaluated using wound healing migration assays, flow cytometry and western blotting. Results: Our study indicates that CDDP inhibits 786-O cell proliferation and migration and HWG and RA protect against these effects. On the other hand, HWG and RA demonstrate a low cytotoxic effect in human renal proximal tubular epithelial cell line -2 (HK-2 cells). Cell cycle analysis found that HWG/CDDP and RA/CDDP combined treatment exerted cytotoxicity by inducing G2/M arrest and apoptosis. RA in combined with CDDP significantly inhibiting the expression of p-FAK (Tyr 925) in RCC 786-O cells in vitro.Conclusion: We propose that the inhibition of RA on RCC 786-O cell invasion and migration may partly occur through the downregulation of FAK phosphorylation. The HWG/CDDP and RA/CDDP combined treatments may be effective strategies for intervention of RCC 786-O cell activity.

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Section: Discussionmentioning

confidence: 76%

“…Combination therapy, which is a treatment modality combining two or more therapeutic agents is a cornerstone in cancer therapy and has provided highly effective results [9][10][11][12].…”

mentioning

confidence: 99%

Bidirect effects from cisplatin combine with rosmarinic acid (RA) or hot water extracts of Glechoma hederacea (HWG) on renal cancer cells

Chou

Tai

et al. 2020

Preprint

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show abstract

“…The combination of anti-tumor agents should be able to produce synergistic or additive therapeutic efficacies, reduced side effects and minimal drug resistance. Experimental strategies that investigate combinational therapy of CDDP with natural plant extracts/plant-derived agents to maintain the desired antitumor efficacy have been reported [9,36,37]. In this study, HWG in combination with CDDP inhibits the invasion of these RCC cells, especially at a concentration of more than 100 µg/mL and inhibited the wound-healing migration of these RCC cells, especially at a concentration of more than 200 µg/mL.…”

Section: Discussionmentioning

confidence: 79%

Bidirect effects from cisplatin combine with rosmarinic acid (RA) or hot water extracts of Glechoma hederacea (HWG) on renal cancer cells

Chou

Tai

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Cisplatin (CDDP) is a chemotherapeutic drug which also causes adverse side effects.Glechoma hederacea is a traditional Chinese herb belonging to the Labiatae family and has many biological activities. Our previous study indicated that rosmarinic acid (RA) was the most abundant phytochemical in G. hederacea. However, the antioxidant or anti-inflammatory effects of the combined treatment of G. hederacea, RA and CDDP on human renal cell carcinoma (RCC) 786-O cells have not been clearly demonstrated. We aimed to investigate the bioefficacy of hot water extracts of G. hederacea (HWG) and RA in inhibiting RCC 786-O cell activity and its synergism with CDDP against metastatic renal cancer cell. Methods:Bioactivities of the combination treatment of HWG, RA, HWG/CDDP and RA/CDDP were assessed using the MTT assay and transwell migration, and the crude extract/compound efficacy was evaluated using wound healing migration assays, flow cytometry and western blotting. Results: Our study indicates that CDDP inhibits 786-O cell proliferation and migration and HWG and RA protect against these effects. On the other hand, HWG and RA demonstrate a low cytotoxic effect in human renal proximal tubular epithelial cell line -2 (HK-2 cells). Cell cycle analysis found that HWG/CDDP and RA/CDDP combination treatment exerted cytotoxicity by inducing G2/M arrest and apoptosis. RA in combination with CDDP significantly inhibit the expression of p-FAK (Tyr 925) in RCC 786-O cells in vitro. Conclusion: We propose that the inhibition of RA on RCC 786-O cell invasion and migration may partly occur through the downregulation of FAK phosphorylation. The HWG/CDDP and RA/CDDP combination treatments may be effective strategies for intervention of RCC 786-O cell activity. BackgroundRenal cell carcinoma (RCC) is the most common type of kidney malignancy and accounts for ~ 3% of tumors in adults. However, only 2% RCC cases are associated with inherited gene mutations. It is also associated with a high metastatic potential [1,2]. RCC is the most lethal genitourinary cancer and patients with metastatic RCC have poor overall survival profiles [3]. 7075% renal cancers are clear cell carcinomas, which have traditionally been resistant to chemo-or radiotherapy [4]. One of the

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“…Derived from the medicinal plant Elephantopus scaber, deoxyelephantopin (DET) is a germacranolide sesquiterpene lactone with antineoplastic property. To study whether the co-therapy of DET and cisplatin could reduce the cisplatin-induced nephrotoxicity, a UPLC/ESI-QTOF MS-based metabolomics of kidney tissues from murine B16 metastatic allograft model in vivo was conducted [89]. It was shown that co-therapy of DET and cisplatin could reverse the changed urea cycle metabolites and hippuric acid in renal tissues caused by cisplatin, revealing that the co-therapy of DET and cisplatin could be an effective treatment with low toxicity for melanoma.…”

Section: Other Related Metabolismsmentioning

confidence: 99%

Chinese Medicines for Cancer Treatment from the Metabolomics Perspective

Guo¹,

Tan²,

Wang³

et al. 2020

Metabolomics - New Insights Into Biology and Medicine

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Cancer is one of the most prevalent diseases all over the world with poor prognosis and the development of novel therapeutic strategies is still urgently needed. The large amount of successful experiences in fighting against cancer-like diseases with Chinese medicine has suggested it as a great source of alternative treatments to human cancers. Cancer cells have been shown to own a predominantly unique metabolic phenotype to facilitate their rapid proliferation. Metabolic reprogramming is a remarkable hallmark of cancer and therapies targeting cancer metabolism can be highly specific and effective. Based on the sophisticated study of small molecule metabolites, metabolomics can provide us valuable information on dynamically metabolic responses of living systems to certain environmental condition. In this chapter, we systematically reviewed recent studies on metabolism-targeting anticancer therapies based on metabolomics in terms of glucose, lipid, amino acid, and nucleotide metabolisms and other altered metabolisms, with special emphasis on the potential of metabolic treatment with pure compounds, herb extracts, and formulations from Chinese medicines. The trends of future development of metabolism-targeting anticancer therapies were also discussed. Overall, the elucidation of the underlying molecular mechanism of metabolism-targeting pharmacologic therapies will provide us a new insight to develop novel therapeutics for cancer treatment.

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Phyto-sesquiterpene lactone deoxyelephantopin and cisplatin synergistically suppress lung metastasis of B16 melanoma in mice with reduced nephrotoxicity

Cited by 21 publications

References 32 publications

Bidirect effects from cisplatin combine with rosmarinic acid (RA) or hot water extracts of Glechoma hederacea (HWG) on renal cancer cells

Bidirect effects from cisplatin combine with rosmarinic acid (RA) or hot water extracts of Glechoma hederacea (HWG) on renal cancer cells

Bidirect effects from cisplatin combine with rosmarinic acid (RA) or hot water extracts of Glechoma hederacea (HWG) on renal cancer cells

Chinese Medicines for Cancer Treatment from the Metabolomics Perspective

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