Sulforaphane inhibits HDAC activity in prostate cancer cells, retards growth of PC3 xenografts, and inhibits HDAC activity
            <i>in vivo</i>

Myzak, Melinda C.; Hardin, Karin; Yan, Michelle; Tong, Philip; Dashwood, Wan‐Mohaiza; Ho, Emily

doi:10.1096/fasebj.20.4.a150

Cited by 10 publications

(12 citation statements)

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“…83 Inhibition of HDAC has been shown for ITCs both in vitro and in vivo in animal models and may alter tumorigenesis. [84][85][86][87][88] Associations between inhibition of HDAC activity and increases in gene expression have been demonstrated with the tumor suppressor gene p21 89,90 and the pro-apoptotic gene Bax. 84 Interestingly, it appears that SFN metabolites (sulforaphane-cysteine and sulforaphane-N-acetyl cysteine) rather than the parent compound may be responsible for the inhibition, possibly by acting as competitive inhibitors.…”

Section: Epigenetic Regulationmentioning

confidence: 99%

Mechanisms of action of isothiocyanates in cancer chemoprevention: an update

2011

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Isothiocyanates, derived from glucosinolates, are thought to be responsible for the chemoprotective actions conferred by higher cruciferous vegetable intake. Evidence suggests that isothiocyanates exert their effects through a variety of distinct but interconnected signaling pathways important for inhibiting carcinogenesis, including those involved in detoxification, inflammation, apoptosis, and cell cycle and epigenetic regulation, among others. This article provides an update on the latest research on isothiocyanates and these mechanisms, and points out remaining gaps in our understanding of these events. Given the variety of ITC produced from glucosinolates, and the diverse pathways on which these compounds act, a systems biology approach, in vivo, may help to better characterize their integrated role in cancer prevention. In addition, the effects of dose, duration of exposure, and specificity of different ITC should be considered.

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Section: Epigenetic Regulationmentioning

confidence: 99%

Mechanisms of action of isothiocyanates in cancer chemoprevention: an update

2011

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“… Liver toxicity: SFN has been shown to have hepatoprotective effects, but the combination treatment of SFN and PTX could increase the risk of liver toxicity [ 55 , 56 ]. Drug interactions: SFN has been shown to induce phase II detoxification enzymes, which can increase the metabolism of drugs metabolized by these enzymes [ 57 ]. This could potentially decrease the efficacy of other drugs taken concurrently with PTX and SFN, or increase the toxicity of these drugs.…”

Section: Discussionmentioning

confidence: 99%

Optimizing combination therapy in prostate cancer: mechanistic insights into the synergistic effects of Paclitaxel and Sulforaphane-induced apoptosis

Habib,

Altonsy,

Ghanem

et al. 2024

BMC Mol and Cell Biol

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Background Combination therapies in cancer treatment have demonstrated synergistic or additive outcomes while also reducing the development of drug resistance compared to monotherapy. This study explores the potential of combining the chemotherapeutic agent Paclitaxel (PTX) with Sulforaphane (SFN), a natural compound primarily found in cruciferous vegetables, to enhance treatment efficacy in prostate cancer. Methods Two prostate cancer cell lines, PC-3 and LNCaP, were treated with varying concentrations of PTX, SFN, and their combination. Cell viability was assessed using the thiazolyl blue tetrazolium bromide (MTT) assay to determine the EC50 values. Western blot analysis was conducted to evaluate the expression of Bax, Bcl2, and Caspase-3 activation proteins in response to individual and combined treatments of PTX and SFN. Fluorescent microscopy was employed to observe morphological changes indicative of apoptotic stress in cell nuclei. Flow cytometry analysis was utilized to assess alterations in cell cycle phases, such as redistribution and arrest. Statistical analyses, including Student’s t-tests and one-way analysis of variance with Tukey’s correction, were performed to determine significant differences between mono- and combination treatments. Results The impact of PTX, SFN, and their combination on cell viability reduction was evaluated in a dose-dependent manner. The combined treatment enhanced PTX’s effects and decreased the EC50 values of both drugs compared to individual treatments. PTX and SFN treatments differentially regulated the expression of Bax and Bcl2 proteins in PC-3 and LNCaP cell lines, favoring apoptosis over cell survival. Our data indicated that combination therapy significantly increased Bax protein expression and the Bax/Bcl2 ratio compared to PTX or SFN alone. Flow cytometry analysis revealed alterations in cell cycle phases, including S-phase arrest and an increased population of apoptotic cells. Notably, the combination treatments did not have a discernible impact on necrotic cells. Signs of apoptotic cell death were confirmed through Caspase-3 cleavage, and morphological changes in cell nuclei were assessed via western blot and fluorescent microscopy. Conclusion This combination therapy of PTX and SFN has the potential to improve prostate cancer treatment by minimizing side effects while maintaining efficacy. Mechanistic investigations revealed that SFN enhances PTX efficacy by promoting apoptosis, activating caspase-3, inducing nuclear morphology changes, modulating the cell cycle, and altering Bax and Bcl2 protein expression. These findings offer valuable insights into the synergistic effects of PTX and SFN, supporting the optimization of combination therapy and providing efficient therapeutic strategies in preclinical research.

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“…In humans, oral intake of broccoli leads to HDACi in PBMCs (determined by HDAC activity and acetylation of H3 and H4) already after 3h and returned to normal levels after 24h (69). Importantly, no severe adverse events or changes in laboratory parameters were observed in a clini-cal trial (72).…”

Section: Sulforaphanementioning

confidence: 98%

“…In xenograft models (e.g. prostate cancer, osteosarcoma), sulforaphane leads to growth retardation, inhibition of HDAC activity, and increase in acetylated H3 and H4 levels (64,69). Furthermore, an antiangiogenic effect has been reported in vitro (70).…”

Section: Sulforaphanementioning

confidence: 99%

Overview of Major Classes of Plant-Derived Anticancer Drugs

Amin,

Gali-Muhtasib,

Ocker

et al. 2009

Int. J Biomed Sci.

153

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Cancer is the second leading cause of death worldwide. Conventional cancer therapies cause serious side effects and, at best, merely extend the patient's lifespan by a few years. Cancer control may therefore benefit from the potential that resides in alternative therapies. The demand to utilize alternative concepts or approaches to the treatment of cancer is therefore escalating. There is compelling evidence from epidemiological and experimental studies that highlight the importance of compounds derived from plants "phytochemicals" to reduce the risk of colon cancer and inhibit the development and spread of tumors in experimental animals. More than 25% of drugs used during the last 20 years are directly derived from plants, while the other 25% are chemically altered natural products. Still, only 5-15% of the approximately 250,000 higher plants have ever been investigated for bioactive compounds. The advantage of using such compounds for cancer treatment is their relatively non-toxic nature and availability in an ingestive form. An ideal phytochemical is one that possesses anti-tumor properties with minimal toxicity and has a defined mechanism of action. As compounds that target specific signaling pathways are identified, researchers can envisage novel therapeutic approaches as well as a better understanding of the pathways involved in disease progression. Here, we focus on 4 classes of natural anticancer drugs: methyltransferase inhibitors, DNA damaging/pro-oxidant drugs, HDAC inhibitors (HDACi), and mitotic disrupters, and we will focus on the mode of action for one promising example per group.

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Sulforaphane inhibits HDAC activity in prostate cancer cells, retards growth of PC3 xenografts, and inhibits HDAC activity in vivo

Cited by 10 publications

References 0 publications

Mechanisms of action of isothiocyanates in cancer chemoprevention: an update

Mechanisms of action of isothiocyanates in cancer chemoprevention: an update

Optimizing combination therapy in prostate cancer: mechanistic insights into the synergistic effects of Paclitaxel and Sulforaphane-induced apoptosis

Overview of Major Classes of Plant-Derived Anticancer Drugs

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