Cockle Shell-Derived Aragonite CaCO3 Nanoparticles for Co-Delivery of Doxorubicin and Thymoquinone Eliminates Cancer Stem Cells

Ibiyeye, Kehinde Muibat; Zuki, A.B.Z.

doi:10.3390/ijms21051900

Cited by 17 publications

(12 citation statements)

References 47 publications

(70 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To generate spheroids serum-free condition was applied to prevent the differentiation of stem-like cells and elimination of non-CSCs population using suspension culturing in low attachment plates [55][56][57][58]. Although, both cell lines showed capacity to form spheroids, the HT-29 cells generated loose and disintegrating spheres in poly-HEMA plates, whereas, they formed compact spheroids when were cultured as hanging drops.…”

Section: Discussionmentioning

confidence: 99%

Morphological and Molecular Characteristics of Spheroid Formation in HT-29 and Caco-2 Colorectal Cancer Cell Lines

Gheytanchi

Naseri

Karimi‐Busheri

et al. 2021

Preprint

View full text Add to dashboard Cite

Background: Relapse and metastasis in colorectal cancer (CRC) are often attributed to cancer stem-like cells (CSCs), as small sub-population of tumor cells with ability of drug resistance. Accordingly, development of appropriate models to investigate CSCs biology and establishment of effective therapeutic strategies is warranted. Hence, we aimed to assess the capability of two widely used and important colorectal cancer cell lines, HT-29 and Caco-2, in generating spheroids and their detail morphological and molecular characteristics.Methods: CRC spheroids were developed using hanging drop and forced ﬂoating in serum-free and non-attachment condition and their morphological features were evaluated by scanning electron microscopy (SEM). Then, the potential of CSCs enrichment in spheroids was compared to their adherent counterparts by analysis of serial sphere formation capacity, real-time PCR of key stemness genes (KLF4, OCT4, SOX2, NANOG, C-MYC) and the expression of potential CRC-CSCs surface markers (CD166, CD44, and CD133) by flow cytometry. Finally, the expression level of some EMT-related (Vimentin, SNAIL1, TWIST1, N-Cadherin, E-Cadherin, ZEB1) and multi-drug resistant (ABCB1, ABCC1, ABCG2) genes was evaluated.Results: Although with different morphological features, both cell lines were formed CSCs-enriched spheroids, indicated by ability to serial sphere formation, significant up-regulation of stemness genes, SOX2, C-MYC, NANOG and OCT4 in HT-29 and SOX2, C-MYC and KLF4 in Caco-2 spheroids (p-value<0.05) and increased expression of CRC-CSC markers compared to parental cells (p-value<0.05). Additionally, HT-29 spheroids exhibited a signiﬁcant higher expression of both ABCB1 and ABCG2 (p-value=0.02). The significant up-regulation of promoting EMT genes, ZEB1, Twist1, E-cadherin and SNAIL1 in HT-29 spheroids (p-value=0.03), SNAIL1 and Vimentin in Caco-2 spheroids (p-value<0.05) and N-cadherin down-regulation in both spheroids were observed.Conclusion: Based on enrichment of CSC-related features in HT-29 and Caco-2 spheroids, our findings suggest CRC spheroids culture as simple, cost-effective and efficient model to imitate the complexity of in vivo CRC tumors including self-renewal, drug resistance and invasion potential for CSC research.

show abstract

Section: Discussionmentioning

confidence: 99%

Morphological and Molecular Characteristics of Spheroid Formation in HT-29 and Caco-2 Colorectal Cancer Cell Lines

Gheytanchi

Naseri

Karimi‐Busheri

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…A Soluplus ® -Solutol ® HS15 micelles formulation enhanced the antimigratory efficacy of TQ (1.5–10 µM) through improving aqueous solubility (10 times) and encapsulation efficacy, as investigated in SH-SY5Y human neuroblastoma cells [ 185 ]. The synergistic potential of TQ loaded in cockle-shell-derived aragonite CaCl 3 -NPs was reported with doxorubicin to reduce cellular migration in mammary gland carcinoma stem cells (MDA MB 231) [ 186 ]. A cubosomal formulation of TQ improved cellular accumulation, which leads to increased apoptotic activity migration in mammary gland carcinoma cell lines (MDA-MB-231 and MCF-7) [ 187 ].…”

Section: Neoplasm and Its Pathogenesismentioning

confidence: 99%

Recent Findings on Thymoquinone and Its Applications as a Nanocarrier for the Treatment of Cancer and Rheumatoid Arthritis

et al. 2021

View full text Add to dashboard Cite

Cancer causes a considerable amount of mortality in the world, while arthritis is an immunological dysregulation with multifactorial pathogenesis including genetic and environmental defects. Both conditions have inflammation as a part of their pathogenesis. Resistance to anticancer and disease-modifying antirheumatic drugs (DMARDs) happens frequently through the generation of energy-dependent transporters, which lead to the expulsion of cellular drug contents. Thymoquinone (TQ) is a bioactive molecule with anticancer as well as anti-inflammatory activities via the downregulation of several chemokines and cytokines. Nevertheless, the pharmacological importance and therapeutic feasibility of thymoquinone are underutilized due to intrinsic pharmacokinetics, including short half-life, inadequate biological stability, poor aqueous solubility, and low bioavailability. Owing to these pharmacokinetic limitations of TQ, nanoformulations have gained remarkable attention in recent years. Therefore, this compilation intends to critically analyze recent advancements in rheumatoid arthritis and cancer delivery of TQ. This literature search revealed that nanocarriers exhibit potential results in achieving targetability, maximizing drug internalization, as well as enhancing the anti-inflammatory and anticancer efficacy of TQ. Additionally, TQ-NPs (thymoquinone nanoparticles) as a therapeutic payload modulated autophagy as well as enhanced the potential of other drugs when given in combination. Moreover, nanoformulations improved pharmacokinetics, drug deposition, using EPR (enhanced permeability and retention) and receptor-mediated delivery, and enhanced anti-inflammatory and anticancer properties. TQ’s potential to reduce metal toxicity, its clinical trials and patents have also been discussed.

show abstract

“…This was accompanied by the reduction of breast CSCs markers CD44 and CD24 expression and aldehyde dehydrogenase 1 activity. In addition, the dual drugs loaded ACNP suppressed breast CSCs migration and invasion[ 157 ]. In colorectal cancer, combination of TQ and 5-FU as well as their hybrid SARB downregulated two major stem cell regulatory pathways Wnt/β-catenin and PI3K/Akt.…”

Section: Tq Effects Against Cancer Stem Cellsmentioning

confidence: 99%

Therapeutic potential of thymoquinone in combination therapy against cancer and cancer stem cells

Fatfat¹,

Fatfat²,

Gali‐Muhtasib³

2021

WJCO

View full text Add to dashboard Cite

The long-term success of standard anticancer monotherapeutic strategies has been hampered by intolerable side effects, resistance to treatment and cancer relapse. These monotherapeutic strategies shrink the tumor bulk but do not effectively eliminate the population of self-renewing cancer stem cells (CSCs) that are normally present within the tumor. These surviving CSCs develop mechanisms of resistance to treatment and refuel the tumor, thus causing cancer relapse. To ensure durable tumor control, research has moved away from adopting the monotreatment paradigm towards developing and using combination therapy. Combining different therapeutic modalities has demonstrated significant therapeutic outcomes by strengthening the anti-tumor potential of monotreatment against cancer and cancer stem cells, mitigating their toxic adverse effects, and ultimately overcoming resistance. Recently, there has been growing interest in combining natural products from different sources or with clinically used chemotherapeutics to further improve treatment efficacy and tolerability. Thymoquinone (TQ), the main bioactive constituent of Nigella sativa, has gained great attention in combination therapy research after demonstrating its low toxicity to normal cells and remarkable anticancer efficacy in extensive preclinical studies in addition to its ability to target chemoresistant CSCs. Here, we provide an overview of the therapeutic responses resulting from combining TQ with conventional therapeutic agents such as alkylating agents, antimetabolites and antimicrotubules as well as with topoisomerase inhibitors and non-coding RNA. We also review data on anticancer effects of TQ when combined with ionizing radiation and several natural products such as vitamin D3, melatonin and other compounds derived from Chinese medicinal plants. The focus of this review is on two outcomes of TQ combination therapy, namely eradicating CSCs and treating various types of cancers. In conclusion, the ability of TQ to potentiate the anticancer activity of many chemotherapeutic agents and sensitize cancer cells to radiotherapy makes it a promising molecule that could be used in combination therapy to overcome resistance to standard chemotherapeutic agents and reduce their associated toxicities.

show abstract

Cockle Shell-Derived Aragonite CaCO3 Nanoparticles for Co-Delivery of Doxorubicin and Thymoquinone Eliminates Cancer Stem Cells

Cited by 17 publications

References 47 publications

Morphological and Molecular Characteristics of Spheroid Formation in HT-29 and Caco-2 Colorectal Cancer Cell Lines

Morphological and Molecular Characteristics of Spheroid Formation in HT-29 and Caco-2 Colorectal Cancer Cell Lines

Recent Findings on Thymoquinone and Its Applications as a Nanocarrier for the Treatment of Cancer and Rheumatoid Arthritis

Therapeutic potential of thymoquinone in combination therapy against cancer and cancer stem cells

Contact Info

Product

Resources

About