Sapodilla Plum (Achras sapota) Induces Apoptosis in Cancer Cell Lines and Inhibits Tumor Progression in Mice

Srivastava, Mrinal; Hegde, Mahesh; Chiruvella, Kishore K.; Koroth, Jinsha; Bhattacharya, Souvari; Choudhary, Bibha; Raghavan, Sathees C.

doi:10.1038/srep06147

Cited by 51 publications

(49 citation statements)

References 38 publications

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“…Cytotoxicity was assessed using the Trypan Blue dye exclusion assay as described before [67][68][69][70][71]. Briefly, HeLa, MCF7, Nalm6, and N114 cells (25 000 mL À1 ) were seeded and treated with SCR7-cyclized or SCR7-pyrazine (50, 100, and 250 lM for 48 h).…”

Section: Cytotoxicity Assaymentioning

confidence: 99%

Autocyclized and oxidized forms of SCR7 induce cancer cell death by inhibiting nonhomologous DNA end joining in a Ligase IV dependent manner

et al. 2018

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Nonhomologous DNA end joining (NHEJ) is the major DNA double-strand break (DSB) repair pathway in mammals. Previously, we have described a small molecule inhibitor, SCR7, which can inhibit NHEJ in a Ligase IV-dependent manner. Administration of SCR7 within the cells resulted in the accumulation of DNA breaks, cell death, and inhibition of tumor growth in mice. In the present study, we report that parental SCR7, which is unstable, can be autocyclized into a stable form. Both parental SCR7 and cyclized SCR7 possess the same molecular weight (334.09) and molecular formula (C H N OS), whereas its oxidized form, SCR7-pyrazine, possesses a different molecular formula (C H N OS), molecular weight (332.07), and structure. While cyclized form of SCR7 showed robust inhibition of NHEJ in vitro, both forms exhibited efficient cytotoxicity. Cyclized and oxidized forms of SCR7 inhibited DNA end joining catalyzed by Ligase IV, whereas their impact was minimal on Ligase III, Ligase I, and T4 DNA Ligase-mediated joining. Importantly, both forms inhibited V(D)J recombination, although the effect was more pronounced for SCR7-cyclized. Both forms blocked NHEJ in a Ligase IV-dependent manner leading to the accumulation of DSBs within the cells. Although cytotoxicity due to SCR7-cyclized was Ligase IV specific, the pyrazine form exhibited nonspecific cytotoxicity at higher concentrations in Ligase IV-null cells. Finally, we demonstrate that both forms can potentiate the effect of radiation. Thus, we report that cyclized and oxidized forms of SCR7 can inhibit NHEJ in a Ligase IV-dependent manner, although SCR7-pyrazine is less specific to Ligase IV inside the cell.

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Section: Cytotoxicity Assaymentioning

confidence: 99%

Autocyclized and oxidized forms of SCR7 induce cancer cell death by inhibiting nonhomologous DNA end joining in a Ligase IV dependent manner

et al. 2018

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“…Tumor size was measured using vernier calipers on alternative days for tumor animals and tumor volume was calculated using the formula V = 0.5 × a × b2, where ‘a’ and ‘b’ indicates the major and minor diameter, respectively. At the end of 28th day of experimental period, animals from each group were sacrificed to collect kidney, liver, thigh and spleen were collected from Paclitaxel, BLEA treated, tumor and normal animals and were evaluated for morphological changes using hematoxylin-eosin stained histological slides (Srivastava et al, 2014a).…”

Section: Methodsmentioning

confidence: 99%

Semecarpus anacardiumLinn. leaf extract exhibits activities against breast cancer and prolongs the survival of tumor-bearing mice

Singh¹,

Ranjan²,

Tripathi³

et al. 2020

Preprint

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Background: Semecarpus anacardium Linn. is a commonly used Ayurvedic medicinal plant. Their different parts including nuts, have various medicinal properties to treat clinical ailments such as vitiligo, inflamation, microbial infection, geriatric problem, baldness and neuro-related problems.Aim of the study: The main objective of this study was an evaluation of the anticancer activity of the leaves of Semecarpus anacardium Linn and phytochemical screening. Materials and methods: The phytochemical screening was carried out through GC-MS analysis. Cytotoxicity was examined using MTT assay whereas mode of cell death evaluated by fluorescence microscopy. Finally, antitumor activity was determined in EAC cell-induced tumorbearing mice. Results: The ethyl acetate extract induced cytotoxicity in cancer cells in a dose dependent manner (IC 50 : 0.57 µg/ml in MCF-7 cells) in different cancer cell lines. However, normal cells were relatively insensitive to the extract. Fluorescence microscopy results, confirmed that the extract induced apoptosis in cancer cells effectively. The extract induce cell cycle arrest at the G1 phase and suppressed cancer cell migration. An oral administration of the extract suppressed the tumor growth in the mice model bearing Ehrlich ascites carcinoma cells. Whereas, the ethyl acetate extract was also found to prolong the survival of tumor-bearing mice. Conclusion: Overall, these observations suggest the anticancer activities of the ethyl acetate extract of S. anacardium leaves. The study opens a new window to examine the phytochemical constituents from the leaves as a source for the anticancer compounds.

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“…Briefly, Nalm6 cells (50,000 cells/ml) were treated with 5g (0, 5, 15 and 30 µM) for 48 h and stained with annexin-FITC/PI using annexin staining kit (Santacruz, USA); cells were processed for FACS analysis and confocal microscopy as described 35, 36 . DMSO treated cells were used as vehicle control.…”

Section: Methodsmentioning

confidence: 99%

A Benzothiazole Derivative (5g) Induces DNA Damage And Potent G2/M Arrest In Cancer Cells

Hegde

Vartak

Kavitha

et al. 2017

Sci Rep

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Chemically synthesized small molecules play important role in anticancer therapy. Several chemical compounds have been reported to damage the DNA, either directly or indirectly slowing down the cancer cell progression by causing a cell cycle arrest. Direct or indirect reactive oxygen species formation causes DNA damage leading to cell cycle arrest and subsequent cell death. Therefore, identification of chemically synthesized compounds with anticancer potential is important. Here we investigate the effect of benzothiazole derivative (5g) for its ability to inhibit cell proliferation in different cancer models. Interestingly, 5g interfered with cell proliferation in both, cell lines and tumor cells leading to significant G2/M arrest. 5g treatment resulted in elevated levels of ROS and subsequently, DNA double-strand breaks (DSBs) explaining observed G2/M arrest. Consistently, we observed deregulation of many cell cycle associated proteins such as CDK1, BCL2 and their phosphorylated form, CyclinB1, CDC25c etc. Besides, 5g treatment led to decreased levels of mitochondrial membrane potential and activation of apoptosis. Interestingly, 5g administration inhibited tumor growth in mice without significant side effects. Thus, our study identifies 5g as a potent biochemical inhibitor to induce G2/M phase arrest of the cell cycle, and demonstrates its anticancer properties both ex vivo and in vivo.

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Sapodilla Plum (Achras sapota) Induces Apoptosis in Cancer Cell Lines and Inhibits Tumor Progression in Mice

Cited by 51 publications

References 38 publications

Autocyclized and oxidized forms of SCR7 induce cancer cell death by inhibiting nonhomologous DNA end joining in a Ligase IV dependent manner

Autocyclized and oxidized forms of SCR7 induce cancer cell death by inhibiting nonhomologous DNA end joining in a Ligase IV dependent manner

Semecarpus anacardiumLinn. leaf extract exhibits activities against breast cancer and prolongs the survival of tumor-bearing mice

A Benzothiazole Derivative (5g) Induces DNA Damage And Potent G2/M Arrest In Cancer Cells

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