Sulforaphane Inhibits Growth of Human Breast Cancer Cells and Augments the Therapeutic Index of the Chemotherapeutic Drug, Gemcitabine

Hussain, Arif; Mohsin, Javeria; Prabhu, Sathyen A.; Begum, Salema; Nusri, Qurrat El Ain; Harish, Geetganga; Javed, Elham; Khan, Munawwar Ali; Sharma, Chhavi

doi:10.7314/apjcp.2013.14.10.5855

Cited by 42 publications

(30 citation statements)

References 39 publications

(39 reference statements)

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“…It was proposed that these effects were mediated by the reduction of sorafenib-induced NFjB binding by sulforaphane. Although treatment with sulforaphane at varying concentrations resulted in a dose-and time-dependent decrease in cell viability of MCF-7 cells, a combination of sulforaphane and gemcitabine demonstrated the capacity of sulforaphane to enhance the growth inhibitory effects of gemcitabine at sub-lethal doses (116). Administration of sub-lethal doses of sulforaphane (5-10 lM) when used in various combinations with lower doses of gemcitabine (5-10 mM) resulted in a decrease in cell viability that was more pronounced than either of the compounds alone and the combination index (CI) was found to be < 1, indicting synergistic effects.…”

Section: Future Directions and Combinatorial Cancer Management Stratementioning

confidence: 99%

Dietary Sulforaphane in Cancer Chemoprevention: The Role of Epigenetic Regulation and HDAC Inhibition

Tortorella

Royce²,

Licciardi

et al. 2015

Antioxidants & Redox Signaling

174

106

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Significance: Sulforaphane, produced by the hydrolytic conversion of glucoraphanin after ingestion of cruciferous vegetables, particularly broccoli and broccoli sprouts, has been extensively studied due to its apparent health-promoting properties in disease and limited toxicity in normal tissue. Recent Studies: Recent identification of a sub-population of tumor cells with stem cell-like self-renewal capacity that may be responsible for relapse, metastasis, and resistance, as a potential target of the dietary compound, may be an important aspect of sulforaphane chemoprevention. Evidence also suggests that sulforaphane may target the epigenetic alterations observed in specific cancers, reversing aberrant changes in gene transcription through mechanisms of histone deacetylase inhibition, global demethylation, and microRNA modulation. Critical Issues: In this review, we discuss the biochemical and biological properties of sulforaphane with a particular emphasis on the anticancer properties of the dietary compound. Sulforaphane possesses the capacity to intervene in multistage carcinogenesis through the modulation and/or regulation of important cellular mechanisms. The inhibition of phase I enzymes that are responsible for the activation of pro-carcinogens, and the induction of phase II enzymes that are critical in mutagen elimination are well-characterized chemopreventive properties. Furthermore, sulforaphane mediates a number of anticancer pathways, including the activation of apoptosis, induction of cell cycle arrest, and inhibition of NFjB. Future Directions: Further characterization of the chemopreventive properties of sulforaphane and its capacity to be selectively toxic to malignant cells are warranted to potentially establish the clinical utility of the dietary compound as an anticancer compound alone, and in combination with clinically relevant therapeutic and management strategies.

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Section: Future Directions and Combinatorial Cancer Management Stratementioning

confidence: 99%

Dietary Sulforaphane in Cancer Chemoprevention: The Role of Epigenetic Regulation and HDAC Inhibition

Tortorella

Royce²,

Licciardi

et al. 2015

Antioxidants & Redox Signaling

174

106

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“…However, targeting phytochemicals toward specific targets may be more relevant to enhance their efficacy and study dose-related effects, combined with other possible implications. The efficacy of phytochemicals in cancer prevention, alone or in combination, has been shown by many investigators (Catania, Barrajón-Catalán, Nicolosi, Cicirata, & Micol, 2013;Hussain et al, 2013;Kapadia et al, 2013;Ouhtit, Gaur, Abdraboh, Ireland, & Rao, 2013;Singh & Shankar, 2011). The phytochemicals included in this study are described in Table 1.…”

Section: Discussionmentioning

confidence: 98%

Protease activated receptor-2 (PAR2): possible target of phytochemicals

Kakarala

Jamil

2014

Journal of Biomolecular Structure and Dynamics

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The use of phytochemicals either singly or in combination with other anticancer drugs comes with an advantage of less toxicity and minimal side effects. Signaling pathways play central role in cell cycle, cell growth, metabolism, etc. Thus, the identification of phytochemicals with promising antagonistic effect on the receptor/s playing key role in single transduction may have better therapeutic application. With this background, phytochemicals were screened against protease-activated receptor 2 (PAR2). PAR2 belongs to the superfamily of GPCRs and is an important target for breast cancer. Using in silico methods, this study was able to identify the phytochemicals with promising binding affinity suggesting their therapeutic potential in the treatment of breast cancer. The findings from this study acquires importance as the information on the possible agonists and antagonists of PAR2 is limited due its unique mechanism of activation.

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“…17,18 PEITC had been found that reversed the cisplatin resistance in various kinds of cancer cells, [19][20][21][22][23][24] and also had synergistic effects with chemotherapy drugs including paclitaxel 25,26 and gemcitabine. 27 In addition, we had also found that BITC induced apoptosis in Gefitinibresistant lung cancer cells. 28 However, the combination effects and related mechanisms are still need to elucidate.…”

Section: Introductionmentioning

confidence: 88%

Phenethyl isothiocyanate synergistically induces apoptosis with Gefitinib in non–small cell lung cancer cells via endoplasmic reticulum stress‐mediated degradation of Mcl‐1

Zhang

Chen

Cao

et al. 2020

Molecular Carcinogenesis

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Isothiocyanates (ITCs) are natural compounds abundant in cruciferous vegetables.Numerous studies have shown that ITCs exhibit anticancer activity by affecting multiple pathways including apoptosis and oxidative stress, and are expected to be developed into novel anticancer drugs. In our previous studies, we demonstrated that ITCs effectively inhibit the proliferation of non-small cell lung cancer (NSCLC) cells, also induce apoptosis and autophagy. In the present study, we found that phenethyl isothiocyanate (PEITC) had significant synergistic effects with epidermal growth factor receptor tyrosine kinase inhibitor Gefitinib in NSCLC cell lines NCI-H1299 and SK-MES-1; and the degradation of antiapoptotic factor myeloid cell leukemia 1 (Mcl-1) caused by PEITC treatment played key roles in the sensitivity of NSCLC cells to Gefitinib. We further illustrated that PEITC regulated the expression of Mcl-1 through protein kinase RNA-like endoplasmic reticulum kinase (PERK)-eukaryotic translation initiation factor 2α-CHOP-Noxa pathway by a posttranscriptional modulation. Pretreatment with endoplasmic reticulum stress (ER stress) inhibitor tauroursodeoxycholic acid and knockdown of PERK expression attenuated the degradation of Mcl-1 caused by PEITC. In in vivo study, nude mice bearing NCI-H1299 xenograft were administrated with PEITC (50 mg/kg, ip) and Gefitinib (50 mg/kg, ig) for 15 days, the PEITC-Gefitinib combination treatment resulted in a significant synergistic reduction in tumor growth, and significantly induced both ER stress and Mcl-1 degradation in tumor tissues. In conclusion, we explored the prospect of PEITC in improving the efficacy of targeted drug therapy and demonstrated the synergistic effects and underlined mechanisms of PEITC combined with Gefitinib in NSCLC cells treatment. This study provided useful information for developing novel therapy strategies by combination treatment of PEITC with targeted drugs. K E Y W O R D S Gefitinib, Mcl-1, non-small cell lung cancer, phenethyl isothiocyanate, synergistic effect | ZHANG ET AL.

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Sulforaphane Inhibits Growth of Human Breast Cancer Cells and Augments the Therapeutic Index of the Chemotherapeutic Drug, Gemcitabine

Cited by 42 publications

References 39 publications

Dietary Sulforaphane in Cancer Chemoprevention: The Role of Epigenetic Regulation and HDAC Inhibition

Dietary Sulforaphane in Cancer Chemoprevention: The Role of Epigenetic Regulation and HDAC Inhibition

Protease activated receptor-2 (PAR2): possible target of phytochemicals

Phenethyl isothiocyanate synergistically induces apoptosis with Gefitinib in non–small cell lung cancer cells via endoplasmic reticulum stress‐mediated degradation of Mcl‐1

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