Isoquinoline Alkaloid Berberine Exerts its Antineoplastic Activity by Inducing Molecular DNA Damage in HeLa Cells: A Comet Assay Study

Ch, Ganesh; Jagetia, ra; Rao, Antara

doi:10.4172/0974-8369.1000223

Cited by 6 publications

(8 citation statements)

References 49 publications

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“…Our results show that in HDF and in MIA PaCa-2 cells MGMT is upregulated after treatments with berberine for 48 hours, suggesting that these cells activate DNA repair mechanisms in response to a possible genotoxic damage induced by the alkaloid, that we showed it is able to enter the nucleus at high concentration. Consistent with this, it is known that berberine induces DNA damage in Rev3 deficient chicken B lymphocytes clones 2 , in human MG-63 osteosarcoma 31 and in HeLa cells 32 . In U343 glioblastoma cells, the MGMT promoter is methylated and MGMT is not expressed 33 ; we here confirm that MGMT is not transcribed in control cells and we demonstrate that it remains untranscribed in berberine-treated U343 cells.…”

Section: Discussionsupporting

confidence: 68%

Cell-specific pattern of berberine pleiotropic effects on different human cell lines

Agnarelli

Natali

Garcia‐Gil

et al. 2018

Sci Rep

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The natural alkaloid berberine has several pharmacological properties and recently received attention as a potential anticancer agent. In this work, we investigated the molecular mechanisms underlying the anti-tumor effect of berberine on glioblastoma U343 and pancreatic carcinoma MIA PaCa-2 cells. Human dermal fibroblasts (HDF) were used as non-cancer cells. We show that berberine differentially affects cell viability, displaying a higher cytotoxicity on the two cancer cell lines than on HDF. Berberine also affects cell cycle progression, senescence, caspase-3 activity, autophagy and migration in a cell-specific manner. In particular, in HDF it induces cell cycle arrest in G2 and senescence, but not autophagy; in the U343 cells, berberine leads to cell cycle arrest in G2 and induces both senescence and autophagy; in MIA PaCa-2 cells, the alkaloid induces arrest in G1, senescence, autophagy, it increases caspase-3 activity and impairs migration/invasion. As demonstrated by decreased citrate synthase activity, the three cell lines show mitochondrial dysfunction following berberine exposure. Finally, we observed that berberine modulates the expression profile of genes involved in different pathways of tumorigenesis in a cell line-specific manner. These findings have valuable implications for understanding the complex functional interactions between berberine and specific cell types.

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Section: Discussionsupporting

confidence: 68%

Cell-specific pattern of berberine pleiotropic effects on different human cell lines

Agnarelli

Natali

Garcia‐Gil

et al. 2018

Sci Rep

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“…Also they are widely acceptable, would not put an extra foreign substance into the body and can be safely manipulated for human use without toxic manifestations [31]. Most of the chemotherapeutic drugs including DOX kill neoplastic cells by triggering DNA damage into cells [43,44], which can be easily estimated by comet assay [34,39,40,45]. Doxorubicin is a topoisomerase-II inhibitor that exerts its cytotoxic effects by stabilizing DNA double strand breaks in the cellular genome [46].…”

Section: Discussionmentioning

confidence: 99%

“…A dose-dependent increase in DNA damage with increasing concentration of DOX is indicated by a significant rise in the tail DNA and OTM. Berberine a topoisomerase II inhibitor has been found to increase DNA damage in HeLa cells [45]. AME has been reported to reduce DOX-induced DNA damage in V79 cells and mice bone marrow cells earlier [14,15].…”

Section: Discussionmentioning

confidence: 99%

Alteration in the Doxorubicin-Induced DNA Damage in Cultured V79 Cells by Aegle marmelos (L.) Correa (Bael): A Comet Assay Study

Jagetia¹

2015

Int J Neurorehabilitation Eng

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The clinical applicability of wide spectrum chemotherapeutic drug, doxorubicin is limited due to induction of severe cardiomyopathy resulting from DNA damage. The present study was aimed to evaluate the protective effect of bael (Aegle marmelos) extract (AME) on the doxorubicin-induced molecular DNA damage in V79 cells. V79 (Chinese hamster lung fibroblasts) cells were treated with 0 or 25 µg/ml AME before exposure to 0, 1, 2.5, 5, 10, 25 or 50 μg/ml doxorubicin DOX. The DNA damage was studied at different post-doxorubicin treatment times using single cell gel electrophoresis. Doxorubicin caused a maximum DNA damage at 1 h post-DOX treatment indicated by a highest Olive Tail Movement (OTM) and tail DNA, whereas treatment of V79 cells with 25 µg/ml AME enhanced DNA repair at all assessment times with a maximum repair up to 8 h which did not alter thereafter. In another experiment DOX caused a concentration dependent increase in the DNA damage and treatment of V79 cells with 25 µg/ml AME significantly inhibited DOX-induced DNA damage at all post-DOX treatment times. The rate of DNA repair was higher in AME pre-treated cells than DOX-treatment alone. Assessment of cell survival showed a concentration dependent decline in the clonogenicity after DOX-treatment, whereas AME pre-treatment arrested the DOX-induced reduction in the cell survival. The DNA damage and clonogenicity of cells showed a close but inverse relationship, i.e., with increasing DNA damage there was a corresponding reduction in the cell survival. This relationship between cell survival and DNA damage was linear quadratic. Our study demonstrates that AME pretreatment reduced the DOX-induced DNA damage and hastened the DNA repair in V79 cells, thus demonstrating the chemoprotective potential of AME.

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“…In agreement, some natural compounds have been shown to reduce colonies formation in different types of cancer. For instance, analogs of the monocelline C alkaloid inhibited the colonies formation of breast cancer cell (de Lima et al, 2017) and berbeline chloride decreased the number of ovarian cancer cell colonies (Jagetia & Rao, 2015).…”

Section: Kopsanone Inhibits Hct-116 Cell Colonies Formationmentioning

confidence: 99%

Kopsanone inhibits proliferation and migration of invasive colon cancer cells

Bonfim

Nakamura

Júnior

et al. 2021

Phytotherapy Research

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Colorectal cancer (CRC) is the second leading cause of cancer-related death globally.In spite of the increasing knowledge on molecular characteristics of different cancer types including CRC, there is limitation in the development of an effective treatment.The present study aimed to verify the antitumor effect of kopsanone, an indole alkaloid. To achieve this, we treated human colon cancer cells (Caco-2 and HCT-116) with kopsanone and analyzed its effects on cell viability, cell-cell adhesion, and actin cytoskeleton organization. In addition, functional assays including micronuclei formation, colony formation, cell migration, and invasiveness were performed. We observed that kopsanone reduced viability and proliferation and induced micronuclei formation of HCT-116 cells. Also, kopsanone inhibited anchorage-dependent colony formation and modulated adherens junctions (AJs), thus increasing the localization of E-cadherin and β-catenin in the cytosol of the invasive cells. Finally, fluorescence assays showed that kopsanone decreased stress fibers formation and reduced migration but not invasion of HCT-116 cells. Taken together, these findings indicate that kopsanone reduces proliferation and migration of HCT-116 cells via modulation of AJs and can therefore be considered for future in vivo and clinical investigation as potential therapeutic agent for treatment of CRC.

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Isoquinoline Alkaloid Berberine Exerts its Antineoplastic Activity by Inducing Molecular DNA Damage in HeLa Cells: A Comet Assay Study

Cited by 6 publications

References 49 publications

Cell-specific pattern of berberine pleiotropic effects on different human cell lines

Cell-specific pattern of berberine pleiotropic effects on different human cell lines

Alteration in the Doxorubicin-Induced DNA Damage in Cultured V79 Cells by Aegle marmelos (L.) Correa (Bael): A Comet Assay Study

Kopsanone inhibits proliferation and migration of invasive colon cancer cells

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