Induction of apoptosis in human cancer cell lines by diospyrin, a plant-derived bisnaphthoquinonoid, and its synthetic derivatives

Chakrabarty, Sutapa; Roy, Madhumita; Hazra, Banasri; Bhattacharya, R.K.

doi:10.1016/s0304-3835(02)00494-9

Cited by 52 publications

(22 citation statements)

References 27 publications

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“…Azaanthraquinone compound such as laoticuzanone A, isolated from the stems of Goniothalamus laoticus have also been shown to exhibit cytotoxicity against HeLa cells with IC 50 values of 0.50 μg/ml (Tip-Pyang et al, 2010). Diospyrin, a bisnaphthoquinonoid natural product show similar result of apotosis induction, chromatin condensation and nuclear fragmentation on HeLa cells and the apoptosis was believed to be mediated via activation of caspase-3 and caspase-8 (Chakrabarty et al, 2002).…”

Section: Naphthoquinone Estersmentioning

confidence: 99%

Roles of Plant Extracts and Constituents in Cervical Cancer Therapy

Kma

2013

Asian Pacific Journal of Cancer Prevention

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Section: Naphthoquinone Estersmentioning

confidence: 99%

Roles of Plant Extracts and Constituents in Cervical Cancer Therapy

Kma

2013

Asian Pacific Journal of Cancer Prevention

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“…Plants of the genus Diospyros (from dios, divine, and pyros, heat; i.e., celestial food) are rich in secondary metabolites, and for this reason, they have frequently been used in folk medicine since ancient times to treat various diseases or symptoms (for review, see Mallavadhani et al, 1998). This compound and its derivatives have revealed interesting antitumor activities (Hazra et al, 1984(Hazra et al, , 1994Pal et al, 1996;Chakrabarty et al, 2002), and it also has been investigated as an antibacterial (Adeniyi et al, 2000;Lall et al, 2003) and antiparasitic agent, active against Plasmodium falciparum, Leishmania donovani, Trypanosoma cruzi, and Trypanosoma brucei brucei (Hazra et al, 1987(Hazra et al, , 1995Yardley et al, 1996), as well as Pneumocystis carinii (Cushion et al, 2000;Kaneshiro et al, 2000). Diospyrin and synthetic derivatives have been shown to induce apoptosis of different human tumor cells (Chakrabarty et al, 2002), but otherwise the mechanism of action of this compound remains essentially unknown.…”

mentioning

confidence: 99%

Selective Inhibition of Topoisomerase I and Various Steps of Spliceosome Assembly by Diospyrin Derivatives

Tazi¹,

Bakkour²,

Soret³

et al. 2004

Mol Pharmacol

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Pre-mRNA splicing is an essential step of the expression of most metazoan protein-coding genes, which is often regulated in a cell type-specific or developmental manner. We have demonstrated previously that human DNA topoisomerase I, an extensively studied target for anticancer drugs, also has an intrinsic protein kinase activity that specifically phosphorylates proteins involved in splice site selection. Therefore, DNA topoisomerase I was recently shown to play a critical role in alternative splicing. Here, we have exploited these novel properties of DNA topoisomerase I to develop entirely novel diospyrin derivatives targeting its protein kinase activity and thereby modulating pre-mRNA splicing. Although some derivatives indeed inhibit kinase activity of topoisomerase I, they did not block reactions of topoisomerase I on DNA. However, these drugs interfere with camptothecin-dependent topoisomerase I-mediated DNA cleavage, implying that diospyrin derivatives mediate a conformational change of topoisomerase I. It is noteworthy that in vitro splicing reactions revealed that diospyrin derivatives alter various steps of splicing. Some diospyrin derivatives inhibit either the first or the second catalytic step of splicing but not spliceosome assembly, whereas diospyrin itself prevents the formation of full spliceosome. Our data revealed for the first time that diospyrin derivatives are able to stall the dynamic assembly of the spliceosome and open the exciting possibility of using these derivatives to correct aberrant splicing in human genetic diseases.

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“…For example, naphthoquinones have been isolated from Diospyros maritima (Higa et al, 2002), and these types of compounds support cytotoxic properties (Adeniyi et al, 2003;Ganapaty et al, 2006). Furthermore, these compounds induce apoptosis (Chakrabarty et al, 2002) through inhibition of DNA topoisomerases (Ting et al, 2003). However, the metabolites (Buenz, 2007a), specifically the naphthoquinones, that Diospyros species produce vary greatly dependent on the environment the plants are grown in (Gu et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Cytotoxic Properties of Diospyros Seychellarum Extract

Buenz

Bauer²,

Motley

et al. 2007

J. Toxicol. Sci.

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-During a recent botanical expedition in the Seychelles archipelago we identified healers using Diospyros seychellarum as a tonic. Since this plant lacks any medicinal record in the current literature, we assessed the cytotoxic potential of D. seychellarum. Using Jurkat cells as a model system we show, by flow cytometry, that treatment with the leaf extract results in mitochondrial depolarization and subsequent loss of cellular membrane integrity. Additionally, by transmission electron microscopy, we show that treatment with the extract results in chromatin condensation, mitochondrial swelling, and loss of nuclear membrane integrity. Through these morphological and biochemical observations we concluded that the extract of Diospyros seychellarum is able to induce apoptosis. While it is difficult to extrapolate a potential pharmacologic function based on the ethnomedical use as a tonic, the ability of this extract to induce apoptosis warrants further investigation of the medicinal properties of this plant.

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Induction of apoptosis in human cancer cell lines by diospyrin, a plant-derived bisnaphthoquinonoid, and its synthetic derivatives

Cited by 52 publications

References 27 publications

Roles of Plant Extracts and Constituents in Cervical Cancer Therapy

Roles of Plant Extracts and Constituents in Cervical Cancer Therapy

Selective Inhibition of Topoisomerase I and Various Steps of Spliceosome Assembly by Diospyrin Derivatives

Cytotoxic Properties of Diospyros Seychellarum Extract

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