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A Model In Vitro Study Using Hypericin: Tumor-Versus Necrosis-Targeting Property and Possible Mechanisms.

ABSTRACT: Hypericin (Hyp) had been explored as a tumor-seeking agent for years; however, more recent studies showed its necrosis-avidity rather than cancer-seeking property. To further look into this discrepancy, we conducted an in vitro study on Hyp retention in vital and dead cancerous HepG2 and normal LO2 cell lines by measuring the fluorescence intensity and concentration of Hyp in cells. To question the DNA binding theory for its necrosis-avidity, the subcellular distribution of Hyp was also investigated to explore the possible mechanisms of the necrosis avidity. The fluorescence intensity and concentration are significantly higher in dead cells than those in vital cells, and this difference did not differ between HepG2 and LO2 cell lines. Hyp was taken up in vital cells in the early phase and excreted within hours, whereas it was retained in dead cells for more than two days. Confocal microscopy showed that Hyp selectively accumulated in lysosomes rather than cell membrane or nuclei. Hyp showed a necrosis-avid property rather than cancer-targetability. The long-lasting retention of Hyp in dead cells may be associated with halted energy metabolism and/or binding with certain degraded cellular substrates. Necrosis-avidity of Hyp was confirmed, which may be associated with halted energy metabolism in dead LO2 or HepG2 cells.

SUBMITTER: Li Y

PROVIDER: S-EPMC7168897 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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A Model In Vitro Study Using Hypericin: Tumor-Versus Necrosis-Targeting Property and Possible Mechanisms.

Li Yue Y Wang Shuncong S Zhao Yuanyu Y Saiyin Hexige H He Xiaoyan X Zhao Juanzhi J Li Ling L Talebi Ali A Huang Gang G Ni Yicheng Y

Biology 20200107 1

Hypericin (Hyp) had been explored as a tumor-seeking agent for years; however, more recent studies showed its necrosis-avidity rather than cancer-seeking property. To further look into this discrepancy, we conducted an in vitro study on Hyp retention in vital and dead cancerous HepG2 and normal LO2 cell lines by measuring the fluorescence intensity and concentration of Hyp in cells. To question the DNA binding theory for its necrosis-avidity, the subcellular distribution of Hyp was also investig ...[more]

PMID: 31936002

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Project description:Main conclusionShoot tip necrosis is a physiological condition that negatively impacts the growth and development of in vitro plant shoot cultures across a wide range of species. Shoot tip necrosis is a physiological condition and disorder that can arise in plantlets or shoots in vitro that results in death of the shoot tip. This condition, which can spread basipetally and affect the emergence of axillary shoots from buds lower down the stem, is due to the cessation of apical dominance. STN can occur at both shoot multiplication and rooting stages. One of the most common factors that cause STN is nutrient deficiency or imbalance. Moreover, the presence or absence of plant growth regulators (auxins or cytokinins) at specific developmental stages may impact STN. The cytokinin to auxin ratio within an in vitro plant can be modified by varying the concentration of cytokinins used in the culture medium. The supply of nutrients to in vitro shoots or plantlets might also affect their hormonal balance, thus modifying the occurrence of STN. High relative humidity within culture vessels and hyperhydricity are associated with STN. An adequate supply of calcium as the divalent cation (Ca2+) can hinder STN by inhibiting the accumulation of phenolic compounds and thus programmed cell death. Moreover, the level of Ca2+ affects auxin transport and ethylene production, and higher ethylene production, which can occur as a result of high relative humidity in or poor ventilation of the in vitro culture vessel, induces STN. High relative humidity can decrease the mobility of Ca2+ within a plant, resulting in Ca2+ deficiency and STN. STN of in vitro shoots or plantlets can be halted or reversed by altering the basal medium, mainly the concentration of Ca2+, adjusting the levels of auxins or cytokinins, or modifying culture conditions. This review examines the literature related to STN, seeks to discover the associated factors and relations between them, proposes practical solutions, and attempts to better understand the mechanism(s) underlying this condition in vitro.

Dataset Information

A Model In Vitro Study Using Hypericin: Tumor-Versus Necrosis-Targeting Property and Possible Mechanisms.

Publications

A Model In Vitro Study Using Hypericin: Tumor-Versus Necrosis-Targeting Property and Possible Mechanisms.

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