Ivermectin Augments the Anti-Cancer Activity of Pitavastatin in Ovarian Cancer Cells

Jawad, Mohammed J.; Richardson, Alan

doi:10.3390/diseases11010049

Cited by 3 publications

(2 citation statements)

References 37 publications

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“…This follows its approval by the U.S. Food and Drug Administration (FDA) and the European Union for the treatment of rosacea. Emerging literature highlights the potential use of ivermectin as a promising candidate for anticancer therapy [26][27][28][29]. Several studies have addressed its antiviral activity against a diverse range of viruses, leading to its exploration for use in treating SARS-CoV-2 during the most recent global pandemic [30].…”

Section: Introductionmentioning

confidence: 99%

Ivermectin: A Multifaceted Drug With a Potential Beyond Anti-parasitic Therapy

Kaur,

Blavo,

Parmar

2024

Cureus

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Ivermectin was first discovered in the 1970s by Japanese microbiologist Satoshi Omura and Irish parasitologist William C. Campbell. Ivermectin has become a versatile pharmaceutical over the past 50 years. Ivermectin is a derivative of avermectin originally used to treat parasitic infections. Emerging literature has suggested that its role goes beyond this and may help treat inflammatory conditions, viral infections, and cancers. Ivermectin's anti-parasitic, anti-inflammatory, anti-viral, and anticancer effects were explored. Its traditional mechanism of action in parasitic diseases, such as scabies and malaria, rests on its ability to interfere with the glutamate-gated chloride channels in invertebrates and the lack of P-glycoprotein in many parasites. More recently, it has been discovered that the ability of ivermectin to block the nuclear factor kappa-light-chain enhancer of the activated B (NF-κB) pathway that modulates the expression and production of proinflammatory cytokines is implicated in its role as an anti-inflammatory agent to treat rosacea. Ivermectin has also been evaluated for treating infections caused by viruses, such as SARS-CoV-2 and adenoviruses, through inhibition of viral protein transportation and acting on the importin α/β1 interface. It has also been suggested that ivermectin can inhibit the proliferation of tumorigenic cells through various pathways that lead to the management of certain cancers. The review aimed to evaluate its multifaceted effects and potential clinical applications beyond its traditional use as an anthelmintic agent.

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Section: Introductionmentioning

confidence: 99%

Ivermectin: A Multifaceted Drug With a Potential Beyond Anti-parasitic Therapy

Kaur,

Blavo,

Parmar

2024

Cureus

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“…The main reason for using an in vitro model is that there have been limited studies on pitavastatin (PITA) combinations with anti-cancer drugs in the cervical cancer cell line (HeLa). The main purpose of using the HeLa cell line is to study the role of PITA in the treatment of cervical cancer, as it gives successful results in different cancer treatments (Jawad & Richardson, 2023).…”

mentioning

confidence: 99%

Pitavastatin induces caspase‐mediated apoptotic death through oxidative stress and DNA damage in combined with cisplatin in human cervical cancer cell line

Hacıseyitoğlu,

Doğan,

Dilsiz

et al. 2023

J of Applied Toxicology

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Pitavastatin (PITA) is a 3‐hydroxy‐3‐methylglutaryl‐CoA (HMG‐CoA) reductase inhibitor to treat hypercholesterolemia and in recent studies is focused that its potential anti‐cancer effect. This study was aimed to elucidate the effect of PITA alone and in combination with cisplatin on cervical cancer cells (HeLa) in vitro. Cytotoxicity of PITA (5–200 μM) was evaluated by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) and neutral red uptake (NRU) assays for 24, 48, and 72 h. Cell apoptosis and cell cycle analyses were performed in flow cytometry (0.1–100 μM). The evaluation of genotoxic effects and oxidative DNA damage of PITA (2–200 μM) were performed with standard comet assay, formamidopyrimidine glycosylase (fpg)‐modified comet assay, and reactive oxygen species (ROS) activation in HeLa cells. PITA alone reduced cell viability in a dose‐dependent manner (20–200, 20–200, and 5–200 μM for 24, 48, and 72 h, respectively, in MTT). The combined treatment of PITA with cisplatin resulted in significantly greater inhibition of cell viability. ROS and DNA damage increased significantly at 100 μM for 4 h and 20 μM for 24 h, respectively. PITA‐induced apoptosis, an increased proportion of sub G1 cells, was monitored, and also, it increased the expression of active caspase‐9 and caspase‐3 and upregulated cleaved poly adenosine diphosphate ribose polymerase (PARP) by western blotting and caspase 3/8/9 multiple assay kit. We conclude that PITA can be used to efficiently cervical cancer studies, and promising findings have been obtained for further studies.

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Molecular Mechanisms Underlying the Anticancer Properties of Pitavastatin against Cervical Cancer Cells

Chen,

Wu,

Yang

et al. 2024

IJMS

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Cervical cancer ranks as the fourth most prevalent form of cancer and is a significant contributor to female mortality on a global scale. Pitavastatin is an anti-hyperlipidemic medication and has been demonstrated to exert anticancer and anti-inflammatory effects. Thus, the purpose of this study was to evaluate the anticancer effect of pitavastatin on cervical cancer and the underlying molecular mechanisms involved. The results showed that pitavastatin significantly inhibited cell viability by targeting cell-cycle arrest and apoptosis in Ca Ski, HeLa and C-33 A cells. Pitavastatin caused sub-G1- and G0/G1-phase arrest in Ca Ski and HeLa cells and sub-G1- and G2/M-phase arrest in C-33 A cells. Moreover, pitavastatin induced apoptosis via the activation of poly-ADP-ribose polymerase (PARP), Bax and cleaved caspase 3; inactivated the expression of Bcl-2; and increased mitochondrial membrane depolarization. Furthermore, pitavastatin induced apoptosis and slowed the migration of all three cervical cell lines, mediated by the PI3K/AKT and MAPK (JNK, p38 and ERK1/2) pathways. Pitavastatin markedly inhibited tumor growth in vivo in a cancer cell-originated xenograft mouse model. Overall, our results identified pitavastatin as an anticancer agent for cervical cancer, which might be expanded to clinical use in the future.

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Ivermectin Augments the Anti-Cancer Activity of Pitavastatin in Ovarian Cancer Cells

Cited by 3 publications

References 37 publications

Ivermectin: A Multifaceted Drug With a Potential Beyond Anti-parasitic Therapy

Ivermectin: A Multifaceted Drug With a Potential Beyond Anti-parasitic Therapy

Pitavastatin induces caspase‐mediated apoptotic death through oxidative stress and DNA damage in combined with cisplatin in human cervical cancer cell line

Molecular Mechanisms Underlying the Anticancer Properties of Pitavastatin against Cervical Cancer Cells

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