Plumbagin improves the efficacy of androgen deprivation therapy in prostate cancer: A pre‐clinical study

Abedinpour, Parisa; Baron, Véronique; Chrastina, Adrian; Rondeau, Gaelle; Pelayo, J Torriente; Welsh, John; Borgström, Per

doi:10.1002/pros.23428

Cited by 29 publications

(17 citation statements)

References 38 publications

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“…A mouse prostate tumor model was used to compare several plumbagin administration schedules as previously described. [8,9] As shown in Figure S8, and consistent with previous findings, per oral plumbagin at 1 mg/kg caused tumors to shrink over time. Similar efficacy was observed when plumbagin was administered once/day, every 3 days or every 5 days, whereas administration every 7 days was less efficient at decreasing tumor size than other schedules.…”

Section: Discussionsupporting

confidence: 90%

“…[50] A second target of plumbagin that is especially pertinent to prostate cancer, for which plumbagin is in clinical trial, is the androgen receptor. Plumbagin has been shown previously to inhibit AR expression [9] and to decrease the hormone-induced expression of AR target genes. [30] It is shown here that plumbagin-BSA indeed decreased AR expression in PTEN-P2 prostate cancer cells.…”

Section: Discussionmentioning

confidence: 96%

“…We have shown previously that in prostate cancer cells, plumbagin decreases the protein expression of the androgen receptor (AR) [9] and decreases the hormone-induced expression of AR target genes. [30] This is particularly relevant to the effect of plumbagin in prostate cancer because prostate tumors depend on the AR axis for growth.…”

Section: Biological Effect Of Plumbagin-albuminmentioning

confidence: 99%

“…In prostate cancer for example, plumbagin was most effective in combination with androgen deprivation therapy, which is the clinical standard of care for hormone-dependent prostate cancer. [8,9] Plumbagin has now entered clinical trial for the treatment of prostate cancer in combination with androgen deprivation therapy. [10] The pharmacodynamic properties of plumbagin are fundamental for its efficacy in the clinic.…”

Section: Introductionmentioning

confidence: 99%

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Plumbagin‐Serum Albumin Interaction: Spectral, Electrochemical, Structure‐Binding Analysis, Antiproliferative and Cell Signaling Aspects with Implications for Anticancer Therapy

et al. 2020

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Plumbagin (5‐hydroxy‐2‐methyl‐1,4‐naphthoquinone) is a small molecule with potent anticancer activity. Like other 1,4‐naphthoquinones, it exhibits electrophilic reactivity towards biological nucleophiles. We demonstrate that plumbagin and structurally related 1,4‐naphthoquinones with at least one unsubstituted quinoid carbon (C2 or C3) bind to albumin, an ubiquitously present nucleophile, with minimum recovery of free drug. Extraction recovery of plumbagin from albumin in solution showed one‐phase exponential decline with a half‐live of 9.3 min at 10 μmol/L. In the presence of albumin, plumbagin exhibited instant changes in UV/Vis absorption bands. Electrochemical analysis using cyclic voltammetry showed a decrease in redox peak currents over time until electro‐inactivity, thus suggesting the formation of a supramolecular adduct inaccessible for electron transfer. The adduct inhibited cell growth and caused cell‐cycle arrest of prostate cancer cells, in part by decreasing levels of the cell‐cycle regulator RBBP. The conjugate displayed similar cellular effects to those described for plumbagin, such as decreased levels of androgen receptor and protein kinase C epsilon. The effect of plumbagin‐albumin on cancer cells was species‐specific, suggesting a receptor‐mediated mechanism. Furthermore, it was blocked by cathepsin inhibitor pepstatin A, indicating that lysosomal degradation is involved in the processing of plumbagin‐albumin adduct. The spontaneously formed adduct of plumbagin with serum albumin is likely to mediate the biological activities of plumbagin in vivo and to fundamentally influence its pharmacodynamics.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 96%

Section: Biological Effect Of Plumbagin-albuminmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Plumbagin‐Serum Albumin Interaction: Spectral, Electrochemical, Structure‐Binding Analysis, Antiproliferative and Cell Signaling Aspects with Implications for Anticancer Therapy

et al. 2020

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“…It has been demonstrated that inhibition of the phosphorylation of STAT3 and JAK2 can lead to the apoptosis of cancer cells (23). The expression levels of JAK2 and STAT3 were assessed by western blot analysis.…”

Section: Sch B Induces Inhibition Of Ar Il6-and Stat3 Induced Stat3 mentioning

confidence: 99%

Inhibitory effects of Schisandrin�B on human prostate cancer cells

et al. 2018

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Prostate cancer is a serious affliction worldwide. Although much progress has been made in the study of prostate cancer prevention and treatment, less attention has been paid to the molecular mechanism of the disease. The molecular arrangement by which Schisandrin B (Sch B) induces human prostate cancer cytotoxicity was comprehensively examined in the present study. As indicated by the results of flow cytometric and western blot analysis, Sch B could inhibit prostate cancer cell proliferation and promote DU145 and LNCaP cell apoptosis and S-phase cell arrest. Moreover, real-time PCR, flow cytometry and western blot result revealed that the cell apoptosis process induced by Sch B in LNCaP cells was associated with its capacity to generate oxidative stress, its inhibition of androgen receptor and the phosphorylation of PI3K/AKT and STA3/JAK2. The data from the present study demonstrated the antitumor effects and the potential pharmacological application of Sch B as an efficient drug for prostate cancer.

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The phytochemical plumbagin: mechanism behind its “pleiotropic” nature and potential as an anticancer treatment

Panda,

Biswal

2024

Arch Toxicol

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Plumbagin improves the efficacy of androgen deprivation therapy in prostate cancer: A pre‐clinical study

Abstract: Plumbagin significantly improves the effect of ADT drugs currently used in the clinic, with few side effects in mice.

Cited by 29 publications

References 38 publications

Plumbagin‐Serum Albumin Interaction: Spectral, Electrochemical, Structure‐Binding Analysis, Antiproliferative and Cell Signaling Aspects with Implications for Anticancer Therapy

Plumbagin‐Serum Albumin Interaction: Spectral, Electrochemical, Structure‐Binding Analysis, Antiproliferative and Cell Signaling Aspects with Implications for Anticancer Therapy

Inhibitory effects of Schisandrin�B on human prostate cancer cells

The phytochemical plumbagin: mechanism behind its “pleiotropic” nature and potential as an anticancer treatment

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