Discovery of thalicthuberine as a novel antimitotic agent from nature that disrupts microtubule dynamics and induces apoptosis in prostate cancer cells

Levrier, Claire; Rockstroh, Anja; Gabrielli, Brian; Kavallaris, Maria; Lehman, Melanie; Davis, Rohan A.; Sadowski, Martin C.; Nelson, Colleen C.

doi:10.1080/15384101.2017.1356512

Cited by 13 publications

(13 citation statements)

References 62 publications

(73 reference statements)

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“…The lower degree of tumor necrosis, less mitotic activity and better definition of tumor borders, sometimes showing areas of peritumoral fibrosis. The mitotic index provides evidence about tumor proliferative activity; the formation of areas of necrosis is often associated with cell proliferation so intense and rapid that neovascularization does not occur with the speed necessary to provide nutrition to tumor cells and, thus, suggesting high proliferative activity; lymphocytic peritumoral fibrosis provide evidence about the interaction between tumor and host tissues [ 54 ]. Thus, it is possible to speculate that such findings, almost not observed in the other groups, could be related to a less aggressive biological behavior of tumors treated with 5-FU and POH/β-CD (50 mg/kg).…”

Section: Resultsmentioning

confidence: 99%

Anti-Tumor Efficiency of Perillylalcohol/β-Cyclodextrin Inclusion Complexes in a Sarcoma S180-Induced Mice Model

et al. 2021

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The low solubility and high volatility of perillyl alcohol (POH) compromise its bioavailability and potential use as chemotherapeutic drug. In this work, we have evaluated the anticancer activity of POH complexed with β-cyclodextrin (β-CD) using three complexation approaches. Molecular docking suggests the hydrogen-bond between POH and β-cyclodextrin in molar proportion was 1:1. Thermal analysis and Fourier-transform infrared spectroscopy (FTIR) confirmed that the POH was enclosed in the β-CD cavity. Also, there was a significant reduction of particle size thereof, indicating a modification of the β-cyclodextrin crystals. The complexes were tested against human L929 fibroblasts after 24 h of incubation showing no signs of cytotoxicity. Concerning the histopathological results, the treatment with POH/β-CD at a dose of 50 mg/kg promoted approximately 60% inhibition of tumor growth in a sarcoma S180-induced mice model and the reduction of nuclear immunoexpression of the Ki67 antigen compared to the control group. Obtained data suggest a significant reduction of cycling cells and tumor proliferation. Our results confirm that complexation of POH/β-CD not only solves the problem related to the volatility of the monoterpene but also increases its efficiency as an antitumor agent.

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Section: Resultsmentioning

confidence: 99%

Anti-Tumor Efficiency of Perillylalcohol/β-Cyclodextrin Inclusion Complexes in a Sarcoma S180-Induced Mice Model

et al. 2021

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“…Thalicthuberine was isolated from Hernandia albiflora Kubitzki, an Australian endemic tree. This compound was treated to LNCaP (2.5 μM), CEM (5 and 10 μM), and VCR-R (60 μM), and the results showed an increase in caspase3/7 activity [51]. Triterpenoid plectranthoic acid is a dietary compound derived from Ficus microcarpa Linne.…”

Section: Resultsmentioning

confidence: 99%

Dietary Compounds for Targeting Prostate Cancer

et al. 2019

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Prostate cancer is the third most common cancer worldwide, and the burden of the disease is increased. Although several chemotherapies have been used, concerns about the side effects have been raised, and development of alternative therapy is inevitable. The purpose of this study is to prove the efficacy of dietary substances as a source of anti-tumor drugs by identifying their carcinostatic activities in specific pathological mechanisms. According to numerous studies, dietary substances were effective through following five mechanisms; apoptosis, anti-angiogenesis, anti-metastasis, microRNA (miRNA) regulation, and anti-multi-drug-resistance (MDR). About seventy dietary substances showed the anti-prostate cancer activities. Most of the substances induced the apoptosis, especially acting on the mechanism of caspase and poly adenosine diphosphate ribose polymerase (PARP) cleavage. These findings support that dietary compounds have potential to be used as anticancer agents as both food supplements and direct clinical drugs.

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“…Moreover, vinblastine treatment of PCa and CRPC has also been reported in vitro . It decreases the proliferation and induces the apoptosis of PCa cell lines, such as LNCaP and DU145 ( 20 , 21 ). Thus, vinblastine effectively treats PCa and CRPC; however, resistance to vinblastine eventually occurs.…”

Section: Discussionmentioning

confidence: 99%

CCNB1 and AURKA are critical genes for prostate cancer progression and castration-resistant prostate cancer resistant to vinblastine

Chen

Wang

et al. 2022

Front. Endocrinol.

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BackgroundProstate cancer (PCa) is a common malignancy occurring in men. As both an endocrine and gonadal organ, prostate is closely correlated with androgen. So, androgen deprivation therapy (ADT) is effective for treating PCa. However, patients will develop castration-resistant prostate cancer (CRPC) stage after ADT. Many other treatments for CRPC exist, including chemotherapy. Vinblastine, a chemotherapeutic drug, is used to treat CRPC. However, patients will develop resistance to vinblastine. Genetic alterations have been speculated to play a critical role in CRPC resistance to vinblastine; however, its mechanism remains unclear.MethodsVarious databases, such as Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA) and Chinese Prostate Cancer Genome and Epigenome Atlas (CPGEA), were used to collect the RNA-sequence data of PCa and CRPC patients and vinblastine-resistant PCa cells. Using online tools, Metascape and TIMER, the pathways and immune infiltration associated with vinblastine resistance-related genes in PCa were analyzed. The function of these genes was verified in clinical samples and CRPC cells.ResultsUsing GSE81277 dataset, we collected the RNA-sequence data of vinblastine sensitive and resistant LNCaP cells and found nine genes (CDC20, LRRFIP1, CCNB1, GPSM2, AURKA, EBLN2, CCDC150, CENPA and TROAP) that correlated with vinblastine resistance. Furthermore, CCNB1, GPSM2 and AURKA were differently expressed between normal prostate and PCa tissues, even influencing PCa progression. The GSE35988 dataset revealed that CCNB1 and AURKA were upregulated in PCa and CRPC samples. Various genes were also found to affect the survival status of PCa patients based on TCGA. These genes were also related to immune cell infiltration. Finally, we verified the function of CCNB1 and AURKA and observed that they were upregulated in PCa and CRPC clinical samples and increased the sensitivity of CRPC cells to vinblastine.ConclusionCCNB1 and AURKA are central to CRPC resistance to vinblastine and affect PCa progression.

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Discovery of thalicthuberine as a novel antimitotic agent from nature that disrupts microtubule dynamics and induces apoptosis in prostate cancer cells

Cited by 13 publications

References 62 publications

Anti-Tumor Efficiency of Perillylalcohol/β-Cyclodextrin Inclusion Complexes in a Sarcoma S180-Induced Mice Model

Anti-Tumor Efficiency of Perillylalcohol/β-Cyclodextrin Inclusion Complexes in a Sarcoma S180-Induced Mice Model

Dietary Compounds for Targeting Prostate Cancer

CCNB1 and AURKA are critical genes for prostate cancer progression and castration-resistant prostate cancer resistant to vinblastine

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