Isoquinoline Alkaloids: Promising Natural Compounds for Targeting Angiogenesis and Metastasis in Colon Cancer

Malla, Rama Rao; Bhamidipati, Priyamvada

doi:10.1615/oncotherap.2022045086

Cited by 3 publications

(1 citation statement)

References 65 publications

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“…Subsequent in‐depth research has revealed the expanding pharmacological repertoire of SNG, encompassing its antimicrobial, anti‐inflammatory and antihypertensive effects (Ma, Sun, et al, 2017). In recent years, a substantial body of research has demonstrated that SNG is an effective anticancer drug, exhibiting significant antitumour effects through various targets and pathways in multiple cancer types, including gastric cancer (Pallichankandy et al, 2015), prostate cancer (Rahman et al, 2019), lung cancer (Cui et al, 2022), colorectal cancer (Malla & Bhamidipati, 2022), bladder cancer (Han et al, 2013), breast cancer (Su et al, 2021), pancreatic cancer (Ma, Yu, et al, 2017) and human leukaemia (Kuttikrishnan et al, 2019). However, the precise anticancer mechanism of SNG in osteosarcoma remains incompletely understood.…”

Section: Discussionmentioning

confidence: 99%

Sanguinarine induces apoptosis in osteosarcoma by attenuating the binding of STAT3 to the single‐stranded DNA‐binding protein 1 (SSBP1) promoter region

Wang,

Zhu,

Qin

et al. 2023

British J Pharmacology

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Background and PurposeOsteosarcoma, a primary malignant bone tumor prevalent among adolescents and young adults, remains a considerable challenge despite protracted progress made in enhancing patient survival rates over the last forty years. Consequently, the development of novel therapeutic approaches for osteosarcoma is imperative. Sanguinarine (SNG), a compound with demonstrated potent anticancer properties against various malignancies, presents a promising avenue for exploration. Nevertheless, the intricate molecular mechanisms underpinning SNG’s actions in osteosarcoma remain elusive, necessitating further elucidation.Experimental ApproachSingle stranded DNA binding protein 1 (SSBP1) was screened out by differential proteomic analysis. The apoptosis, cell cycle, reactive oxygen species (ROS) and mitochondrial changes were assessed via flow cytometry. Western blotting and qRT‐PCR were used to determine relevant protein and gene levels. The anti‐tumor mechanism of SNG was explored at molecular level using chromatin immunoprecipitation (ChIP) and dual luciferase reporter plasmids.Key ResultsOur investigation revealed that SNG exerted an upregulated effect on SSBP1, disrupting mitochondrial function and inducing apoptosis. In‐depth analysis uncovered a specific mechanism whereby SNG hindered the JAK/STAT3 signaling pathway, relieved the inhibitory effect of STAT3 on SSBP1 transcription and inhibited the downstream PI3K/Akt/mTOR signaling axis, ultimately activating the apoptosis.Conclusion and ImplicationsThe study delved further into elucidating the anti‐cancer mechanism of SNG in the context of osteosarcoma. Notably, we unraveled the previously undisclosed apoptotic potential of SSBP1 in osteosarcoma cells. This finding holds substantial promise in advancing the development of novel anti‐cancer drugs and the identification of therapeutic targets.

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Section: Discussionmentioning

confidence: 99%

Sanguinarine induces apoptosis in osteosarcoma by attenuating the binding of STAT3 to the single‐stranded DNA‐binding protein 1 (SSBP1) promoter region

Wang,

Zhu,

Qin

et al. 2023

British J Pharmacology

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New 5, 6, 7, 8‐Tetrahydro‐Isoquinolines Bearing 2‐Nitrophenyl Group Targeting RET Enzyme: Synthesis, Anticancer Activity, Apoptotic Induction and Cell Cycle Arrest

Saddik,

Bakhite,

Hassanien

et al. 2024

Chemistry & Biodiversity

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In this work, we synthesized new 5,6,7,8‐tetrahydroisoquinolines and 6,7,8,9‐tetrahydrothieno[2,3‐c]isoquinolines derivatives and the structures of these new compounds were confirmed with different spectroscopic techniques. Furthermore, the anticancer activities of these compounds were assessed against eight tumor cell lines and one normal human skin fibroblast cell line (HSF). Subsequently, IC50 values of the synthesized compounds were determined for two specific cancer cell lines. Compound 3 exhibited the most potent antiproliferative activity against the HEPG2 cell line, whereas compound 9c demonstrated superior efficacy against the HCT116 cell line. Moreover, the mechanism of action for compound 3 on HEPG2 cells using flow cytometry and Annexin V‐FITC apoptosis analysis was studied. Compound 3 caused cell cycle arrest at the G2/M with a 50‐fold increase in apoptosis of the HEPG2 cell line. Finally, a molecular docking study was conducted to assess the inhibitory potential of compounds 3 and 7 against the RET enzyme. Results indicated that compounds 3 and 7 bind to the RET enzyme with binding energies of ‐5.2 and ‐5.6 kcal/mol, respectively. While these values suggest inhibitory activity, they are less potent than the standard inhibitor, alectinib, which exhibits a binding energy of ‐7.2 kcal/mol.

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Nitrophenyl-Group-Containing Heterocycles. 2. Synthesis, Characterization, Anticancer Activity, Apoptotic Induction and Cell Cycle Arrest of Some New 5,6,7,8-Tetrahydro-isoquinolines Bearing 2-Nitrophenyl Group

Saddik,

Bakhite,

Hassanien

et al. 2024

Preprint

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In this work 7-Acetyl-4-cyano-1, 6-dimethyl-6-hydroxy-8-(2-nitrophenyl)-5,6,7,8-tetrahydrosoquinoline-3(2H)-thione compound 2 was synthesized and used as starting materials. Subsequently, Compounds 3–7 were produced through its reaction with ethyl iodide, ethyl chloroacetate, chloroacetonitrile, and chloroacetaldehyde. Additionally, compound 2 and 2-chloroacetamide were heated in ethanol with sodium acetate trihydrate present, resulting in the formation of 3-Substituted methylthio-5,6,7,8-tetrahydroisoquinoline-4-carbonitriles 9a–d, respectively. Similarly, compounds 2 and N-(1-naphthyl)-2-chloroacetamide reacted to produce high yields of the equivalent N-(1-naphthyl)-(5,6,7,8-tetrahydroiso-quinolin-3-ylthio)acetamides 9e. Compounds 9a–e were cyclized into their 10a and d. Using elemental analysis and spectral data (FT-IR, 1H NMR, and 13C NMR). All newly synthesized compounds were described. The anticancer activity of the produced compounds was also assessed against eight cell lines at one spot concentration and one normal human skin fibroblast cell line HSF. Then determine the IC50 of our drugs against two specific cell lines using various doses. Compound 3 is the most effective chemical against HEGP2, according to our research. Compound 9c was also the most effective compound against HCT116. For generally, the tested substances showed moderate anticancer activity, according to the data. The effects of compound 3 on the proliferation of HEGP2 cell lines were then investigated using an apoptotic Annexin V-FITC assay and flow cytometry. Compound 3 increased the HEGP2 cell line's apoptosis by 50 times and caused cell cycle arrest at the G2/M phase.

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Isoquinoline Alkaloids: Promising Natural Compounds for Targeting Angiogenesis and Metastasis in Colon Cancer

Cited by 3 publications

References 65 publications

Sanguinarine induces apoptosis in osteosarcoma by attenuating the binding of STAT3 to the single‐stranded DNA‐binding protein 1 (SSBP1) promoter region

Sanguinarine induces apoptosis in osteosarcoma by attenuating the binding of STAT3 to the single‐stranded DNA‐binding protein 1 (SSBP1) promoter region

New 5, 6, 7, 8‐Tetrahydro‐Isoquinolines Bearing 2‐Nitrophenyl Group Targeting RET Enzyme: Synthesis, Anticancer Activity, Apoptotic Induction and Cell Cycle Arrest

Nitrophenyl-Group-Containing Heterocycles. 2. Synthesis, Characterization, Anticancer Activity, Apoptotic Induction and Cell Cycle Arrest of Some New 5,6,7,8-Tetrahydro-isoquinolines Bearing 2-Nitrophenyl Group

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