Apoptosis Induction and Anticancer Activity of 2, 4-bis (1-phenylethyl) Phenol from Clerodendrum thomsoniae Balf.f. in vitro

Vascular endothelial growth factor (VEGF) signals cell survival, cell migration, osteogenesis, cell proliferation, angiogenesis, and vascular permeability by binding to VEGF receptor 2 (VEGFR-2). Osteosarcoma is the most common primary bone cancer, majorly affects young adults. Activation of VEGFR-2 signaling is a therapeutic target for osteosarcoma. The present study aimed to evaluate the potency of stylopine in regulation of the VEGFR-2 signaling pathway and its anti-tumour effect human MG-63 osteosarcoma cells. The in silico study on benzylisoquinoline alkaloids was carried out for analyzing and shortlisting of compounds using a virtual screening, Lipinski’s rule, bioavailability graphical RADAR plot, pharmacokinetics, toxicity, and molecular docking studies. Among the benzylisoquinoline alkaloids, stylopine was selected and subjected to in-vitro studies against human MG-63 osteosarcoma cells. Various experiments such as MTT assay, EtBr/AO staining, mitochondrial membrane potential assessment, transwell migration assay, gene expression analysis by a quantitative real time polymerase chain reaction (qRT-PCR) method, SDS-PAGE followed by immunoblotting were performed to evaluate its anti-tumour effect as compared to standard axitinib. The MTT assay indicates that stylopine inhibits cell proliferation in MG-63 cells. Similarly, as confirmed by the EtBr/Ao staining method, the MMP assay indicates that stylopine induces mitochondrial membrane damage and apoptosis as compared to axitinib. Moreover, stylopine inhibits the VEGF-165 induced MG-63 cell migration by a trans-well migration assay. The immunoblotting and qRT-PCR analysis showed that stylopine inhibits the VEGF-165 induced VEGFR2 expression in MG-63 cells. It is concluded that stylopine has potential to regulate VEGFR2 and can inhibit osteosarcoma cells to offer a new drug candidate for the treatment of bone cancer in future.

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“…The solution was kept protected from any light. Fluorescence was measured at 490/525 nm and 540/590 nm ( Ashraf et al, 2020 ).…”

Section: Methodsmentioning

confidence: 99%

Stylopine: A potential natural metabolite to block vascular endothelial growth factor receptor 2 (VEGFR2) in osteosarcoma therapy

et al. 2023

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“…[20,23] Further studies revealed that phenolic moiety induces apoptotic activity. [24] Eventually, the multicomponent anticancer activity of phenolic moiety has incited us to probe its effect on quinolone carboxamides skeleton.…”

Section: Chemistryselectmentioning

confidence: 99%

“…anticancer activity against human nasopharyngeal cancer (NPC) HK‐1, cervix (HeLa), triple‐negative breast adenocarcinomas (MDA‐MB‐231), lymphoblastic leukaemia (MOLT‐3), colon carcinoma (HCT‐116), hepatocellular liver carcinoma (HEPG‐2), human breast carcinoma (MCF‐7), hepatoma (BEL‐7404), ovarian cancer (OVCAR‐3 and A2780/CP70), and human prostate cancer (DU‐145 and PC‐3) cell lines [20,23] . Further studies revealed that phenolic moiety induces apoptotic activity [24] . Eventually, the multicomponent anticancer activity of phenolic moiety has incited us to probe its effect on quinolone carboxamides skeleton.…”

Section: Introductionmentioning

confidence: 99%

Novel Derivatives of 4,6‐Dihydroxy‐2‐Quinolone‐3‐Carboxamides as Potential PI3Kα Inhibitors

et al. 2022

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The phosphatidylinositol 3‐kinase/protein kinase B (PI3K/AKT) pathway is a crucial pathway in cancer pathogenesis. Novel derivatives of 4,6‐dihydroxy‐2‐quinolone‐3‐carboxamides were synthesized as potential PI3Kα inhibitors. Derivatives’ chemical identity was approved using 1H‐NMR, 13C‐NMR, FTIR, and MS. Cytotoxicity was evaluated on the breast (MCF‐7) and colon cancer (HCT‐116) cell lines using the CCK8 assay. Apoptosis was assessed by Annexin‐PI staining. Western blotting was employed to assess the expression of BcL2, Bax, and the phosphorylation status of AKT. Data revealed that compounds exhibited a dose‐response cytotoxic effect. Compounds 8 b and 8 f showed the lowest IC50 on all cell lines and highest apoptosis levels that were associated with lower BcL2/Bax ratios. Western blot results showed a significant inhibition of pAKT in the treated cells, which could be attributed to PI3Kα inhibitory effects of 8 b and 8 f. In conclusion, our findings indicate that 8 b and 8 f are drug‐like chemical compounds that possess promising anticancer effects.

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Analysis of GC-MS from Acetone Extract of Canarium odontophyllum Miq Stem Bark (Dabai)

Ishak,

Rajab,

Basri

2024

Biomed. Pharmacol. J.

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Canarium odontophyllum or dabai is a natural plant found along the river banks of the Sarikei, Kapit and Kanowit in Sarawak and it comes from the 'Burseraceae' family. C. odontophyllum also known as 'dabai' and this dabai fruit is eaten by the community in Sarawak. The fruit is a seasonal natural fruit that is less used because of its short lifespan. A few studies show that acetone extract of Canarium odontophyllum stem bark (dabai) exhibit antiproliferative and cytotoxicity effect on cancer colorectal cells. However, there is currently no analysis of bioactive compounds in acetone extract of Canarium odontophyllum stem bark (dabai). The various bioactive compounds detected in acetone extract were identified using gas chromatography-mass spectrometry (GC-MS). A total of 24 phytoconstituents were detected in this acetone extract. It was found that major peaks represented bicyclo [3.1.0] hex-2-ene,2-methyl-5-(1-methylethyl)-, bicyclo [3.1.0] hexane,4-methylene-1-(1-methylethyl)-, alpha cubebene, 1H cyclopenta [1,3] cyclopropa [1,2] benzene, octahydro-7-methyl-3-methylene-4-(1-methylethyl)-,[3aS-(3a.alpha., 3b.beta., 4.beta., 7.alpha., 7aS*)]-, phenol,2,4-bis(1,1-dimethylethyl)-, spathulenol, copaene, 9-Eicosene, (E)-, hexadecane, 5-Octadecene, (E)-, hexadecane, 2,6,10,14-tetramethyl-, nonadecane, n-Hexadecanoic acid, heptacosane, 1-chloro-, 9,12-Octadecadienoic acid (Z,Z)-, 9,12-Octadecadienoic acid, ethyl ester, octadecanoic acid, 10-Heneicosene (c,t), heptafluorobutyric acid, hexadecyl ester, dehydroabietic acid, phenol, 2,4-bis(1-phenylethyl)-, beta sitosterol, beta-amyrin and alpha-amyrin. The highest peak area (%) for this acetone extract is alpha-amyrin (16.6644%) followed by beta-amyrin (4.6159%), beta sitosterol (3.3369%) and 9,12-Octadecadienoic acid (Z,Z)- (3.2045%). In conclusion, various bioactive compounds detected in acetone extract of Canarium odontophyllum stem bark (dabai) were demonstrated various medicinal properties while alpha and beta-amyrin may be responsible for the cytotoxicity and apoptotic effect against HCT 116 cell.

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Apoptosis Induction and Anticancer Activity of 2, 4-bis (1-phenylethyl) Phenol from Clerodendrum thomsoniae Balf.f. in vitro

Cited by 3 publications

References 31 publications

Stylopine: A potential natural metabolite to block vascular endothelial growth factor receptor 2 (VEGFR2) in osteosarcoma therapy

Stylopine: A potential natural metabolite to block vascular endothelial growth factor receptor 2 (VEGFR2) in osteosarcoma therapy

Novel Derivatives of 4,6‐Dihydroxy‐2‐Quinolone‐3‐Carboxamides as Potential PI3Kα Inhibitors

Analysis of GC-MS from Acetone Extract of Canarium odontophyllum Miq Stem Bark (Dabai)

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