Natural compounds to overcome cancer chemoresistance: toxicological and clinical issues

Turrini, Eleonora; Ferruzzi, Lorenzo; Fimognari, Carmela

doi:10.1517/17425255.2014.972933

Cited by 52 publications

(34 citation statements)

References 106 publications

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“…A new strategy for GBM chemotherapy which is aimed to increase antitumor responses is the combination of natural compound with TMZ (43). Therefore, the present study was performed to detect the role of SFN in sensitizing chemotherapeutic agents of TMZ in TMZ-resistant glioma cells.…”

Section: Discussionmentioning

confidence: 99%

Sulforaphane reverses chemo-resistance to temozolomide in glioblastoma cells by NF-κB-dependent pathway downregulating MGMT expression

Lan

Yang

Han

et al. 2015

International Journal of Oncology

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Abstract. The survival benefits of patients with glioblastoma (GBM) remain unsatisfactory due to the intrinsic or acquired resistance to temozolomide (TMZ). We elucidated the mechanisms of sulforaphane (SFN) reverse TMZ resistance in TMZ-inducing cell lines by inhibiting nuclear factor-κB (NF-κB) transcriptional activity. TMZ-resistant cell lines (U87-R and U373-R) were generated by stepwise (6 months) exposure of parental cells to TMZ. Luciferase reporter assay, biochemical assays and subcutaneous tumor establishment were used to characterize the antitumor effect of SFN. MGMT expression and 50% inhibiting concentration (IC 50 ) values of TMZ in GBM cell lines were assessed. Next, we established that U87-R and U373-R cells presenting high IC 50 of TMZ, activated NF-κB transcription and significantly increased MGMT expression compared with untreated cells. Furthermore, we revealed that SFN could significantly suppress proliferation of TMZ-resistant GBM cells. In addition, SFN effectively inhibited activity of NF-κB signaling pathway and then reduced MGMT expression to reverse the chemo-resistance to TMZ in T98G, U87-R and U373-R cell lines. Sequential combination with TMZ synergistically inhibited survival capability and increased the induction of apoptosis in TMZ-resistant GBM cells. Finally, a nude mouse model was established with U373-R cell subcutaneous tumor-bearing mice, and results showed that SFN could remarkably suppress cell growth and enhance cell death in chemo-resistant xenografts in the nude mouse model. Collectively, the present study suggests that the clinical efficacy of TMZ-based chemotherapy in TMZ-resistant GBM may be improved by combination with SFN.

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Section: Discussionmentioning

confidence: 99%

Sulforaphane reverses chemo-resistance to temozolomide in glioblastoma cells by NF-κB-dependent pathway downregulating MGMT expression

Lan

Yang

Han

et al. 2015

International Journal of Oncology

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“…Recent studies on the effects of natural compounds against chemoresistance show that they inhibit MDR protein activity or further reduce MDR protein expressions (Turrini, Ferruzzi, & Fimognari, ). Table lists these MDR inhibitors and compounds acting through other mechanisms.…”

Section: Herbal Compounds With the Potential To Synergize With Antitumentioning

confidence: 99%

Natural compounds as potential adjuvants to cancer therapy: Preclinical evidence

Lin

Hsu

Tsai

et al. 2019

British J Pharmacology

235

175

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Traditional chemotherapy is being considered due to hindrances caused by systemic toxicity. Currently, the administration of multiple chemotherapeutic drugs with different biochemical/molecular targets, known as combination chemotherapy, has attained numerous benefits like efficacy enhancement and amelioration of adverse effects that has been broadly applied to various cancer types. Additionally, seeking natural‐based alternatives with less toxicity has become more important. Experimental evidence suggests that herbal extracts such as Solanum nigrum and Claviceps purpurea and isolated herbal compounds (e.g., curcumin, resveratrol, and matairesinol) combined with antitumoral drugs have the potential to attenuate resistance against cancer therapy and to exert chemoprotective actions. Plant products are not free of risks: Herb adverse effects, including herb–drug interactions, should be carefully considered. Linked Articles This article is part of a themed section on The Pharmacology of Nutraceuticals. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.6/issuetoc

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“…Targeting MTA1/HIF-1α signaling by pterostilbene in combination with histone deacetylase inhibitor attenuates prostate cancer progression inhibiting metastasis-associated protein 1 (MTA1) and destabilizing MTA1/HDAC (histone deacetylases 1 and 2) unit of the nucleosome remodeling and deacetylase (NuRD) multiprotein complex, which is involved in chromatin remodeling and gene silencing [2,5,6,15]. From a therapeutic perspective, dietary agents are being intensively studied for their chemosensitizing targeted anticancer properties to achieve an enhanced efficacy [16][17][18][19]. In our previous study, we have shown that combination of resveratrol and clinically approved HDAC inhibitor SAHA (suberoylanilide hydroxamic acid, vorinostat), synergistically increased p53 acetylation resulting in significantly increased apoptosis compared to each agent alone [15].…”

Section: Original Researchmentioning

confidence: 99%

Targeting MTA1/HIF‐1α signaling by pterostilbene in combination with histone deacetylase inhibitor attenuates prostate cancer progression

et al. 2017

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The metastasis‐associated protein 1(MTA1)/histone deacetylase (HDAC) unit is a cancer progression‐related epigenetic regulator, which is overexpressed in hormone‐refractory and metastatic prostate cancer (PCa). In our previous studies, we found a significantly increased MTA1 expression in a prostate‐specific Pten‐null mouse model. We also demonstrated that stilbenes, namely resveratrol and pterostilbene (Pter), affect MTA1/HDAC signaling, including deacetylation of tumor suppressors p53 and PTEN. In this study, we examined whether inhibition of MTA1/HDAC using combination of Pter and a clinically approved HDAC inhibitor, SAHA (suberoylanilide hydroxamic acid, vorinostat), which also downregulates MTA1, could block prostate tumor progression in vivo. We generated and utilized a luciferase reporter in a prostate‐specific Pten‐null mouse model (Pb‐Cre +; Pten f/f; Rosa26 Luc/+) to evaluate the anticancer efficacy of Pter/SAHA combinatorial approach. Our data showed that Pter sensitized tumor cells to SAHA treatment resulting in inhibiting tumor growth and additional decline of tumor progression. These effects were dependent on the reduction of MTA1‐associated proangiogenic factors HIF‐1α, VEGF, and IL‐1β leading to decreased angiogenesis. In addition, treatment of PCa cell lines in vitro with combined Pter and low dose SAHA resulted in more potent inhibition of MTA1/HIF‐1α than by high dose SAHA alone. Our study provides preclinical evidence that Pter/SAHA combination treatment inhibits MTA1/HIF‐1α tumor‐promoting signaling in PCa. The beneficial outcome of combinatorial strategy using a natural agent and an approved drug for higher efficacy and less toxicity supports further development of MTA1‐targeted therapies in PCa.

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Natural compounds to overcome cancer chemoresistance: toxicological and clinical issues

Cited by 52 publications

References 106 publications

Sulforaphane reverses chemo-resistance to temozolomide in glioblastoma cells by NF-κB-dependent pathway downregulating MGMT expression

Sulforaphane reverses chemo-resistance to temozolomide in glioblastoma cells by NF-κB-dependent pathway downregulating MGMT expression

Natural compounds as potential adjuvants to cancer therapy: Preclinical evidence

Targeting MTA1/HIF‐1α signaling by pterostilbene in combination with histone deacetylase inhibitor attenuates prostate cancer progression

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