Preliminary evaluation on the beneficial effects of pioglitazone in the treatment of endometrial cancer

Kumari, Garikapati Kusuma; Kiran, Ammu V. V. V. Ravi; Krishnamurthy, Praveen Thaggikuppe

doi:10.1007/s12032-021-01521-x

Cited by 6 publications

(4 citation statements)

References 40 publications

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“…In addition, the slow release of fluid, peripheral oedema, development of chronic kidney disease, and liver dysfunction promoted by PIO [ 2 , 19 , 20 , 21 ] can be attributed to insufficient production of ATP for ion pumps and exchangers in the plasma membrane. Moreover, the reduction of the mitochondrial Ca 2+ -retention capacity and the cancellation of the suppression of mPTP by adenine nucleotides ( Figure 2 ) can be a reason for the toxicity of PIO in several cell lines [ 23 , 24 , 25 , 26 ]. At the same time, the reduction of the risk of myocardial infarction and stroke in patients with clinical manifestation of cardiovascular disease might be connected with long-term effects of PIO, such as the regulation of autophagy and mitochondrial quality control ( Figure 8 ) [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

“…Liver dysfunctions, including hepatitis, deregulation of the level of hepatic enzymes, and mixed hepatocellular-cholestatic liver injury, as well as liver failure with or without fatal outcomes, have been reported to be associated with the intake of PIO [ 21 ]. Besides, PIO significantly increases the risk of bladder cancer [ 22 ] but can display cytotoxic and cytostatic effects on several cancer cell lines [ 23 , 24 , 25 , 26 ].…”

Section: Introductionmentioning

confidence: 99%

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Pioglitazone Is a Mild Carrier-Dependent Uncoupler of Oxidative Phosphorylation and a Modulator of Mitochondrial Permeability Transition

et al. 2021

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Pioglitazone (PIO) is an insulin-sensitizing antidiabetic drug, which normalizes glucose and lipid metabolism but may provoke heart and liver failure and chronic kidney diseases. Both therapeutic and adverse effects of PIO can be accomplished through mitochondrial targets. Here, we explored the capability of PIO to modulate the mitochondrial membrane potential (ΔΨm) and the permeability transition pore (mPTP) opening in different models in vitro. ΔΨm was measured using tetraphenylphosphonium and the fluorescent dye rhodamine 123. The coupling of oxidative phosphorylation was estimated polarographically. The transport of ions and solutes across membranes was registered by potentiometric and spectral techniques. We found that PIO decreased ΔΨm in isolated mitochondria and intact thymocytes and the efficiency of ADP phosphorylation, particularly after the addition of Ca2+. The presence of the cytosolic fraction mitigated mitochondrial depolarization but made it sustained. Carboxyatractyloside diminished the PIO-dependent depolarization. PIO activated proton transport in deenergized mitochondria but not in artificial phospholipid vesicles. PIO had no effect on K+ and Ca2+ inward transport but drastically decreased the mitochondrial Ca2+-retention capacity and protective effects of adenine nucleotides against mPTP opening. Thus, PIO is a mild, partly ATP/ADP-translocase-dependent, uncoupler and a modulator of ATP production and mPTP sensitivity to Ca2+ and adenine nucleotides. These properties contribute to both therapeutic and adverse effects of PIO.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Pioglitazone Is a Mild Carrier-Dependent Uncoupler of Oxidative Phosphorylation and a Modulator of Mitochondrial Permeability Transition

et al. 2021

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“…Pioglitazone, a non-oncological drug, is a peroxisome proliferator-activated receptor gamma (PPAR-γ) agonist. Compared to the standard paclitaxel treatment, it showed significant dose-dependent anticancer activity against EC induced by N-ethyl-N-nitrosourea (ENU) and estradiol hexadrobenzoate (EHB) [ 345 ].…”

Section: Repurposing Of Existing Drugs In Gynecological Cancersmentioning

confidence: 99%

New insights for gynecological cancer therapies: from molecular mechanisms and clinical evidence to future directions

Zhang

Sheng

Sun

et al. 2023

Cancer Metastasis Rev

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Advanced and recurrent gynecological cancers lack effective treatment and have poor prognosis. Besides, there is urgent need for conservative treatment for fertility protection of young patients. Therefore, continued efforts are needed to further define underlying therapeutic targets and explore novel targeted strategies. Considerable advancements have been made with new insights into molecular mechanisms on cancer progression and breakthroughs in novel treatment strategies. Herein, we review the research that holds unique novelty and potential translational power to alter the current landscape of gynecological cancers and improve effective treatments. We outline the advent of promising therapies with their targeted biomolecules, including hormone receptor-targeted agents, inhibitors targeting epigenetic regulators, antiangiogenic agents, inhibitors of abnormal signaling pathways, poly (ADP-ribose) polymerase (PARP) inhibitors, agents targeting immune-suppressive regulators, and repurposed existing drugs. We particularly highlight clinical evidence and trace the ongoing clinical trials to investigate the translational value. Taken together, we conduct a thorough review on emerging agents for gynecological cancer treatment and further discuss their potential challenges and future opportunities.

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“…In vivo, telmisartan had a significant impact on human endometrial cancer growth, with negligible side effects [45]. Kumari et al applied the PPARγ agonist pioglitazone to female Swiss albino mice with endometrial cancer and noted a significant increase in weekly body weight, improvement in mean survival time, and partial normalization of uterine tissue weight, in comparison with the standard chemotherapeutic agent, paclitaxel [46]. Accordingly, Wu et al treated HEC-1A and Ishikawa cells with rosiglitazone, which inhibited cancer cellular growth and induced apoptosis in a dose-dependent manner [47].…”

Section: The Role Of Pparγ In Endometrial Cancermentioning

confidence: 99%

The Role of Peroxisome Proliferator-Activated Receptors in Endometrial Cancer

Psilopatis

Vrettou

Troungos

et al. 2023

IJMS

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Endometrial carcinoma is the most common malignant tumor of the female genital tract in the United States. Peroxisome proliferator-activated receptors (PPARs) are nuclear receptor proteins which regulate gene expression. In order to investigate the role of PPARs in endometrial cancer, we conducted a literature review using the MEDLINE and LIVIVO databases and were able to identify 27 relevant studies published between 2000 and 2023. The PPARα and PPARβ/δ isoforms seemed to be upregulated, whereas PPARγ levels were reported to be significantly lower in endometrial cancer cells. Interestingly, PPAR agonists were found to represent potent anti-cancer therapeutic alternatives. In conclusion, PPARs seem to play a significant role in endometrial cancer.

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Preliminary evaluation on the beneficial effects of pioglitazone in the treatment of endometrial cancer

Cited by 6 publications

References 40 publications

Pioglitazone Is a Mild Carrier-Dependent Uncoupler of Oxidative Phosphorylation and a Modulator of Mitochondrial Permeability Transition

Pioglitazone Is a Mild Carrier-Dependent Uncoupler of Oxidative Phosphorylation and a Modulator of Mitochondrial Permeability Transition

New insights for gynecological cancer therapies: from molecular mechanisms and clinical evidence to future directions

The Role of Peroxisome Proliferator-Activated Receptors in Endometrial Cancer

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