Goniothalamin induces cell cycle arrest and apoptosis in H400 human oral squamous cell carcinoma: A caspase-dependent mitochondrial-mediated pathway with downregulation of NF-κβ

Li, Lim K.; Ali-Saeed, Rola; Kaid, Fahme A.; Ali, Abdul Manaf; Alabsi, Aied M.

doi:10.1016/j.archoralbio.2015.12.002

Cited by 22 publications

(19 citation statements)

References 42 publications

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“…Importantly, CYP1 family enzymes were not expressed in MCF-10a cells 9 . Thus, eupatorin at 5 μg/mL did not affect the viability of human normal breast MCF-10a cells and was found highly selective towards cancer cells indicated by SI>3 21,22 . Interestingly, although the IC 50 value of eupatorin was far higher than the common anticancer drug doxorubicin on both cancer cell lines, the MCF-10a vs MCF7 and MCF-10a vs MDA-MB-231 SI values of eupatorin were 6.5 and 8.8 times higher than doxorubicin, respectively.…”

Section: Discussionmentioning

confidence: 86%

Cytotoxicity of eupatorin in MCF-7 and MDA-MB-231 human breast cancer cells via cell cycle arrest, anti-angiogenesis and induction of apoptosis

Razak

Abu

et al. 2019

Sci Rep

162

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Eupatorin has been reported with in vitro cytotoxic effect on several human cancer cells. However, reports on the mode of action and detail mechanism of eupatorin in vitro in breast cancer disease are limited. Hence, eupatorin’s effect on the human breast carcinoma cell line MCF-7 and MDA-MB-231 was investigated. MTT assay showed that eupatorin had cytotoxic effects on MCF-7 and MDA-MB-231 cells but was non-toxic to the normal cells of MCF-10a in a time-dose dependent manner. At 24 h, the eupatorin showed mild cytotoxicity on both MCF-7 and MDA-MB-231 cells with IC50 values higher than 20 μg/mL. After 48 h, eupatorin at 5 μg/mL inhibited the proliferation of MCF-7 and MDA-MB-231 cells by 50% while the IC50 of MCF-10a was significantly (p < 0.05) high with 30 μg/mL. The concentration of eupatorin at 5 μg/mL induced apoptosis mainly through intrinsic pathway by facilitating higher fold of caspase 9 compared to caspase 8 at 48 h. The cell cycle profile also showed that eupatorin (5 μg/mL) exerted anti-proliferation activity with the cell cycle arrest of MCF-7 and MDA-MB-231 cells at sub Gθ/G1 in a time-dependent manner. In addition, wound healing assay showed an incomplete wound closure of scratched MDA-MB-231 cells, and more than 60% of the MDA-MB-231 cells were prevented to migrate and invade the membrane in the Boyden chamber after 24 h. Eupatorin also inhibited angiogenic sprouting of new blood vessels in ex vivo mouse aorta ring assay. In gene expression assay, eupatorin up-regulated pro-apoptotic genes such as Bak1, HIF1A, Bax, Bad, cytochrome c and SMAC/Diablo and blocked the Phospho-Akt pathway. In conclusion, eupatorin is a potent candidate to induce apoptosis and concurrently inhibit the invasion, migration and angiogenesis of MDA-MB-231 and MCF-7 cells through inhibition of Phospho-Akt pathway and cell cycle blockade.

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Section: Discussionmentioning

confidence: 86%

Cytotoxicity of eupatorin in MCF-7 and MDA-MB-231 human breast cancer cells via cell cycle arrest, anti-angiogenesis and induction of apoptosis

Razak

Abu

et al. 2019

Sci Rep

162

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“…As recently reviewed, 1 some authors have suggested that DNA damage by GTN action is followed by induced apoptosis. 28 This conclusion was later confronted by other authors, whose results indicated that GTN was responsible for the DNA-induced fragmentation. 29 In our studies, we have not observed the events above, as BTD–GTN ( 1 ) was basically accumulated in the cytosol, more specifically in the mitochondria.…”

Section: Resultsmentioning

confidence: 95%

Preferential Mitochondrial Localization of a Goniothalamin Fluorescent Derivative

et al. 2017

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A fluorescent 2,1,3-benzothiadiazole-containing goniothalamin derivative, BTD−GTN (1), has been synthesized and successfully tested in bioimaging experiments in live cells. The fluorescent compound proved to be capable of transposing the cell membranes, indicating its subcellular localization. The use of the benzothiadiazole core as the fluorophore revealed the favored localization of the GTN analogue 1 in the cytoplasm of live cells, preferentially in the mitochondria, in line with previous results that indicated the loss of mitochondrial transmembrane potential upon treatment with GTN. The results described herein highlight the potential of the BTD–GTN hybrid structures for future studies regarding the cellular mechanism of action of this family of compounds.

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“…Arresting DNA replication at G 0 /G 1 phase can direct the cells either to be repaired or to undergo apoptosis (34)(35)(36). This is the synergistic mechanisms for the cytotoxic effects of cytotoxic agents in cancer cells (37).…”

Section: Discussionmentioning

confidence: 99%

Pereskia bleo Leaves Extract Induces Cell Death via Cell Cycle Arrest and Apoptosis in Cervical Cancer Cells HeLa

Mohd-Salleh

Wan-Ibrahim

Ismail

2019

Nutrition and Cancer

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Introduction: Pereskia bleo is a leafy and edible plant, locally known as "Pokok Jarum Tujuh Bilah" which has anticancer properties. This study purposed to determine the cytotoxic effects of P. bleo leaves extracts on several well-known cancer cells and elucidate its underlying mechanism in inducing cell death. Methods: Cytotoxic activity on selected cell lines was determined using MTT assay. Mechanism of cell death was investigated through cell cycle and Annexin V assay. Expression of apoptotic proteins was measured by flow cytometry method. Results: Ethyl acetate extract of P. bleo leaves (PBEA) appeared to have the strongest IC 50 value (14.37 ± 8.40 lg/ml) and most active against HeLa cells was further studied for apoptosis. The cell cycle investigation by flow cytometry evidenced the increment of PBEA treated HeLa cells in G 0 /G 1 phase and apoptotic event was detected in Annexin V assay. Analysis of apoptotic protein showed pro-apoptotic proteins (Bax, p53 and caspase 3) were triggered where as anti-apoptotic protein Bcl-2 was suppressed in treated HeLa cells. Conclusions: Our findings demonstrated that PBEA treatment induced cell death in HeLa cells by p53-mediated mechanism through arresting cell cycle at G 0 /G 1 phase and mitochondrial-mediated pathway with involvement of pro-apoptotic proteins, anti-apoptotic protein, and caspase 3.

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Goniothalamin induces cell cycle arrest and apoptosis in H400 human oral squamous cell carcinoma: A caspase-dependent mitochondrial-mediated pathway with downregulation of NF-κβ

Cited by 22 publications

References 42 publications

Cytotoxicity of eupatorin in MCF-7 and MDA-MB-231 human breast cancer cells via cell cycle arrest, anti-angiogenesis and induction of apoptosis

Cytotoxicity of eupatorin in MCF-7 and MDA-MB-231 human breast cancer cells via cell cycle arrest, anti-angiogenesis and induction of apoptosis

Preferential Mitochondrial Localization of a Goniothalamin Fluorescent Derivative

Pereskia bleo Leaves Extract Induces Cell Death via Cell Cycle Arrest and Apoptosis in Cervical Cancer Cells HeLa

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