Induced Cell Cycle Arrest in Triple-Negative Breast Cancer by Combined Treatment of Itraconazole and Rapamycin

Wu, Haijian; Li, Chunlan; Fang, Ze-Xuan; Chen, Wen-Jia; Lin, Wenting; Liu, Jing

doi:10.3389/fphar.2022.873131

Cited by 4 publications

(3 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is well known that cyclin proteins activate cyclin-dependent kinases (Cdks), which are crucial in promoting cancer progression by promoting cancer cell proliferation and inhibiting apoptosis 20 . Additionally, strategically triggering cell cycle arrest in the G0/G1 phase potentially addresses the aberrant procession of the tumor cell cycle in TNBC and PDAC 21,22 . In this study, OZ-001 inhibited cancer cell proliferation by reducing cyclin D and CDKs.…”

Section: Discussionmentioning

confidence: 99%

OZ-001 suppresses the growth of triple-negative breast cancer and pancreatic cancer via targeting STAT3 phosphorylation and calcium signaling pathway

Kim,

Lee

et al. 2024

Preprint

View full text Add to dashboard Cite

Background Triple-negative breast cancer (TNBC) and pancreatic ductal adenocarcinoma (PDAC) are characterized by uncontrolled tumor growth, high risk of recurrence and resistance to chemotherapy, and poor prognosis. OZ-001 is a small molecule that exhibits a unique dual mechanism of action by blocking T-type Ca2+ channels and targeting signal transducer and activator of transcription 3(STAT3) activation. This characteristic shows promise in addressing the urgent need for effective treatments in TNBC and PDAC. The study aimed to elucidate the anticancer characteristics, efficacy, and underlying mechanism of action of OZ-001. The finding could provide valuable insights into its therapeutic potential for treating aggressive and poor-prognosis malignancies. Methods The anticancer activities of OZ-001 were evaluated using MDA-MB-231 human TNBC cells and MIA PaCa-2 PDAC cells. In this study, cell viability, apoptosis, protein characterization, and cell cycle analysis were done to understand the influence of OZ-001 on MDA-MB-231 and MIA PaCa-2 cells. Additionally, protein affinity and intracellular calcium measurements were measured to evaluate the functional mechanism of OZ-001 targeting STAT3 and T-type calcium channels. Further, TNBC and PDAC animal models were developed using MDA-MB-231 and MIA PaCa-2 xenograft mice to assess the anticancer effects of OZ-001. Results The study observations revealed that the OZ-001 molecule induced caspase-dependent MDA-MB-231 and MIA PaCa-2 cell death via B-cell lymphoma 2(BCL-2) family proteins. OZ-001 selectively regulated cell viability by suppressing STAT3 phosphorylation-linked genes such as survivin, Mcl-1, and Cyclin D1. Specifically, OZ-001 blocked the T-type calcium channels, which reduced intracellular calcium levels and activated cell death pathways in TNBC and PDAC. Further, oral administration of OZ-001 suppressed tumor growth in MDA-MB-231 and MIA PaCa-2 xenograft mice, which could be attributed to reduced STAT3 phosphorylation and decreased tumor growth. Conclusion The study findings revealed that OZ-001 inhibits the phosphorylation of STAT3 and T-type calcium channels against TNBC and PDAC. These findings suggest the potential therapeutic application of OZ-001 as an alternative anticancer molecule.

show abstract

Section: Discussionmentioning

confidence: 99%

OZ-001 suppresses the growth of triple-negative breast cancer and pancreatic cancer via targeting STAT3 phosphorylation and calcium signaling pathway

Kim,

Lee

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…A combinational therapy of osimertinib with itraconazole (ITR) (NCT02157883) has also been suggested for NSCLC to overcome EGFR-TKI resistance ( Vishwanathan et al, 2018 ). ITR is repurposed for several cancers including prostate, breast, triple-negative breast, ovarian, pancreatic, and lung cancer because of its anticancer properties ( Antonarakis et al, 2013 ; Tsubamoto et al, 2015 ; Alhakamy and Md, 2019 ; Wu et al, 2022 ; Sinsuwan and Norchai, 2023 ). Besides hedgehog pathway inhibition, ITR’s effect on multiple antiangiogenic pathways was reported in an early phase 1 NSCLC study (NCT02357836) ( Gerber et al, 2020 ).…”

Section: Repurposed Drugs Under Clinical Investigation For Nsclcmentioning

confidence: 99%

Non-small Cell Lung Cancer Treatment: Current Status of Drug Repurposing and Nanoparticle-based Drug Delivery Systems

Gul INCI,

ACAR,

BALIK

2024

Turkish Journal of Biology

View full text Add to dashboard Cite

Drug repurposing is the strategy of drug utilization for a treatment option other than the intended indications and has increased over the past decades, especially within cancer nanomedicine. Cancer nanomedicine has been facilitated through nanoparticle-based (NP-based) delivery systems which can combat NSCLC via recent advances in nanotechnology and apply its benefits to existing drugs. An effective therapeutic solution could be gained via repurposing and accelerated via NP-based drug delivery systems. This review aims to present an overview of NSCLC treatments with a special focus on drug repurposing with details of clinical study advances and NP-based drug delivery systems for NSCLC. First, molecular mechanisms of the FDA-approved drugs for NSCLC including ROS1 TKI repotrectinib, which was approved in November 2023, were detailed. Further, in vitro studies utilized the combination strategy of both drug repurposing and np-based drug delivery systems as a treatment strategy against NSCLC is listed including the most recent nanoparticle-based drug delivery system study with a repurposed drug-loaded nanoparticles.

show abstract

“…Recent works have continued to support the potential for itraconazole to inhibit cancer growth [218][219][220][221].…”

Section: The Antifungal Drug Itraconazolementioning

confidence: 99%

The OSR9 Regimen: A New Augmentation Strategy for Osteosarcoma Treatment Using Nine Older Drugs from General Medicine to Inhibit Growth Drive

Kast

2023

IJMS

View full text Add to dashboard Cite

As things stand in 2023, metastatic osteosarcoma commonly results in death. There has been little treatment progress in recent decades. To redress the poor prognosis of metastatic osteosarcoma, the present regimen, OSR9, uses nine already marketed drugs as adjuncts to current treatments. The nine drugs in OSR9 are: (1) the antinausea drug aprepitant, (2) the analgesic drug celecoxib, (3) the anti-malaria drug chloroquine, (4) the antibiotic dapsone, (5) the alcoholism treatment drug disulfiram, (6) the antifungal drug itraconazole, (7) the diabetes treatment drug linagliptin, (8) the hypertension drug propranolol, and (9) the psychiatric drug quetiapine. Although none are traditionally used to treat cancer, all nine have attributes that have been shown to inhibit growth-promoting physiological systems active in osteosarcoma. In their general medicinal uses, all nine drugs in OSR9 have low side-effect risks. The current paper reviews the collected data supporting the role of OSR9.

show abstract

Induced Cell Cycle Arrest in Triple-Negative Breast Cancer by Combined Treatment of Itraconazole and Rapamycin

Cited by 4 publications

References 39 publications

OZ-001 suppresses the growth of triple-negative breast cancer and pancreatic cancer via targeting STAT3 phosphorylation and calcium signaling pathway

OZ-001 suppresses the growth of triple-negative breast cancer and pancreatic cancer via targeting STAT3 phosphorylation and calcium signaling pathway

Non-small Cell Lung Cancer Treatment: Current Status of Drug Repurposing and Nanoparticle-based Drug Delivery Systems

The OSR9 Regimen: A New Augmentation Strategy for Osteosarcoma Treatment Using Nine Older Drugs from General Medicine to Inhibit Growth Drive

Contact Info

Product

Resources

About