Antiproliferative and apoptotic potential of Glycyrrhizin against HPV16+ Caski cervical cancer cells: A plausible association with downreguation of HPV E6 and E7 oncogenes and Notch signaling pathway

Ahmad, Afza; Tiwari, Rohit Kumar; Mishra, Prakriti; Alkhathami, Ali G.; Almeleebia, Tahani M.; Alshahrani, Mohammad Y.; Ahmad, Irfan; Asiri, Rawan Amer; Alabdullah, Noura M; Hussien, Mohamed; Ansari, Irfan Ahmad

doi:10.1016/j.sjbs.2022.01.054

Cited by 7 publications

(22 citation statements)

References 56 publications

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“…Cytotoxicity induced by EtOH-LCa, against A549 cells, was estimated by a tetrazolium dye-based assay as described previously [22]. The assay was initiated by exposing 1 × 10 4 A549 cells to varying concentrations of EtOH-LCa ranging from 0 to 200 µg/mL for 24 h in a sterile cell culture environment.…”

Section: Assessment Of Etoh-lca-mediated Cytotoxicitymentioning

confidence: 99%

“…The potential of EtOH-LCa to alter the nuclear morphology of A549 cells was qualitatively evaluated using Hoechst-33342 stain [22], and 1 × 10 4 A549 cells were exposed to the above-stated concentration of EtOH-LCa for 12 h under optimum culture conditions. After incubation, the media from each well of different groups was decanted and was replaced with Hoechst-33342 for 30 min.…”

Section: Etoh-lca-mediated Effects On Nuclear Morphologymentioning

confidence: 99%

“…Dissipation of mitochondrial membrane potential (∆ψm) impels cytochrome C and apoptosis-inducing factor (AIF) release in the cytoplasm from mitochondria, which are effectual regulators of programmed cell death [22]. We subsequently investigated the effects of EtOH-LCa on mitochondrial membrane potential.…”

Section: Effect Of Etoh-lca On Mitochondrial Membrane Potential In Lu...mentioning

confidence: 99%

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Coleus aromaticus Ethanolic Leaves Extract Mediates Inhibition of NF-κB Signaling Pathway in Lung Adenocarcinoma A549 Cells

et al. 2023

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Lung cancer is the second leading cause of cancer-related mortalities globally. Failure in diagnosis at early stages and limited effective chemotherapeutics has severely impeded the clinical management of patients suffering from lung carcinoma. At present, researchers across the world are focused on exploring biologically active natural products for treating various cancers, which can thus be further investigated for their chemotherapeutical potential. Coleus aromaticus is a common herb used in culinary practices and has previously been shown to possess various medicinal characteristics. In the present study, the anti-cancer effects of ethanolic extract of C. aromaticus leaves (EtOH-LCa) against non-small cell lung carcinoma (NSCLC) A549 cells were screened. It was observed that EtOH-LCa reduced the viability of A549 cells and obstructed the cell cycle progression in a concentration-dependent manner. Importantly, EtOH-LCa succeeded in instigating the production of reactive oxygen species (ROS) (p < 0.001) within A549 cells. The elevation in ROS levels was concomitantly followed by the disruption of nuclear morphology and the loss in mitochondria viability within A549 cells. In addition, EtOH-LCa was successful in increasing the activity of caspases-3, which further aided in increasing apoptosis. Most importantly, EtOH-LCa decreased NF-κB expression (p < 0.05) along with modulating mRNA expression of pro-/anti-apoptotic genes; Bax, Bad, Bcl-2 and Bcl-XL within NSCLC A549 cells. Collectively, it could be concluded that EtOH-LCa possessed considerable anti-cancer effects against NSCLC A549 cells; however, further molecular studies are warranted to completely establish the chemotherapeutical potential of EtOH-LCa.

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Section: Assessment Of Etoh-lca-mediated Cytotoxicitymentioning

confidence: 99%

Section: Etoh-lca-mediated Effects On Nuclear Morphologymentioning

confidence: 99%

Section: Effect Of Etoh-lca On Mitochondrial Membrane Potential In Lu...mentioning

confidence: 99%

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Coleus aromaticus Ethanolic Leaves Extract Mediates Inhibition of NF-κB Signaling Pathway in Lung Adenocarcinoma A549 Cells

et al. 2023

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“…For example, in the case of oncogenic viruses such as HPV, Kaposi's Sarcoma Herpes Virus (KSHV) or Epstein-Barr virus, it has been shown that Gly can interfere with the activity of their viral oncoproteins. On one hand, Gly suppresses the expression of the viral oncoproteins E6 and E7 from HPV [8] and LANA from KSHV [9]. In the cases of HPV and KSHV, suppression of their viral oncoproteins leads to p53 reactivation, increased reactive oxygen species (ROS) and mitochondrial dysfunction, resulting in G1 cell cycle arrest, DNA fragmentation and oxidative stress-mediated apoptosis [8,9].…”

Section: Antiviral Activity Of Glycyrrhizinic Acidmentioning

confidence: 99%

“…On one hand, Gly suppresses the expression of the viral oncoproteins E6 and E7 from HPV [8] and LANA from KSHV [9]. In the cases of HPV and KSHV, suppression of their viral oncoproteins leads to p53 reactivation, increased reactive oxygen species (ROS) and mitochondrial dysfunction, resulting in G1 cell cycle arrest, DNA fragmentation and oxidative stress-mediated apoptosis [8,9]. As for the suppression of the EBV viral oncoprotein LMP1, Gly inhibits the SUMOylation processes derived from LMP1 activity, blocking proliferation, increasing cell death, inducing low levels of viral reactivation and preventing the infection of new cells [10].…”

Section: Antiviral Activity Of Glycyrrhizinic Acidmentioning

confidence: 99%

Glycyrrhizinic Acid as an Antiviral and Anticancer Agent in the Treatment of Human Papillomavirus

Bravo,

Serrano,

Duque

et al. 2023

JPM

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Human papillomavirus (HPV), like any other virus, needs to penetrate the host cell and make use of its machinery to replicate. From there, HPV infection can be asymptomatic or lead to benign and premalignant lesions or even different types of cancer. HPV oncogenesis is due to the ability of the viral oncoproteins E6 and E7 to alter the control mechanisms for the growth and proliferation of host cell. Therefore, the use of agents with the ability to control these processes is essential in the search for effective treatments against HPV infections. Glycyrrhizinic acid (Gly), the active ingredient in liquorice, has been shown in numerous preclinical studies to have an antiviral and anticancer activity, reducing the expression of E6 and E7 and inducing apoptosis in cervical cancer cells. In addition, it also has antioxidant, anti-inflammatory, immunomodulatory or re-epithelializing properties that can be useful in HPV infections. This review includes the different antiviral and anticancer mechanisms described for Gly, as well as the clinical studies carried out that position it as a potential therapeutic strategy against HPV both through its topical application and by oral administration.

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Targeting HSP70‐E7 Interaction With SHetA2: A Novel Therapeutic Strategy for Cervical Cancer

Garland,

Hussain,

Rai

et al. 2024

Journal of Medical Virology

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Cervical cancer is predominantly driven by persistent infections with high‐risk human papillomavirus and the continuous activity of its E6 and E7 oncoproteins. This study explored the role of heat shock proteins 70 kDa (HSP70s) in enhancing the function of these oncoproteins and examined the impact of SHetA2, an investigational new drug, on this interaction. We found that HSP70 specifically binds to E7, but not E6, protein and that SHetA2 disrupts this binding. This disruption led to a significant reduction in E6 and E7 mRNA and E7 protein levels, while effects on E6 protein levels were minimal. SHetA2 treatment also resulted in altered levels of cell cycle regulatory proteins, reduced cell cycle progression, and decreased metabolic viability in cervical cancer cell lines and xenograft models. These findings support the potential of SHetA2 to impair cervical cancer progression by targeting HSP70/E7 interactions, highlighting its promise as a therapeutic strategy for treating cervical cancer.

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Antiproliferative and apoptotic potential of Glycyrrhizin against HPV16+ Caski cervical cancer cells: A plausible association with downreguation of HPV E6 and E7 oncogenes and Notch signaling pathway

Cited by 7 publications

References 56 publications

Coleus aromaticus Ethanolic Leaves Extract Mediates Inhibition of NF-κB Signaling Pathway in Lung Adenocarcinoma A549 Cells

Coleus aromaticus Ethanolic Leaves Extract Mediates Inhibition of NF-κB Signaling Pathway in Lung Adenocarcinoma A549 Cells

Glycyrrhizinic Acid as an Antiviral and Anticancer Agent in the Treatment of Human Papillomavirus

Targeting HSP70‐E7 Interaction With SHetA2: A Novel Therapeutic Strategy for Cervical Cancer

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