Betulinic Acid Kills Colon Cancer Stem Cells

Potze, Lisette; Franco, Simone Di; Kessler, Jan H.; Stassi, Giorgio; Medema, Jan Paul

doi:10.2174/1574888x11666151203223512

Cited by 39 publications

(20 citation statements)

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“…Further supporting our pathway analysis, drug resistance profiles in AA included drugs linked to stem cell and invasion pathways, including betulinic acid, rosiglitazone, and adiphenine. For example, betulinic acid and its derivative have been shown to target cancer stem cells and also have anticancer potential in NSCLC (48)(49)(50). Rosiglitazone, a thiazolidinedione used to treat diabetes, has demonstrated both antitumor and chemopreventive effects (51,52) and is also linked with stem cell signaling (53,54).…”

Section: Discussionmentioning

confidence: 99%

Comparative Transcriptome Profiling Reveals Coding and Noncoding RNA Differences in NSCLC from African Americans and European Americans

Mitchell

Zingone

Toulabi

et al. 2017

Clinical Cancer Research

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To determine whether racial differences in gene and miRNA expression translates to differences in lung tumor biology with clinical relevance in African Americans (AAs) and European Americans (EAs). The NCI-Maryland Case Control Study includes seven Baltimore City hospitals and is overrepresented with AA patients (∼40%). Patients that underwent curative NSCLC surgery between 1998 and 2014 were enrolled. Comparative molecular profiling used mRNA ( = 22 AAs and 19 EAs) and miRNA ( = 42 AAs and 55 EAs) expression arrays to track differences in paired fresh frozen normal tissues and lung tumor specimens from AAs and EAs. Pathway enrichment, predicted drug response, tumor microenvironment infiltration, cancer immunotherapy antigen profiling, and miRNA target enrichment were assessed. AA-enriched differential gene expression was characterized by stem cell and invasion pathways. Differential gene expression in lung tumors from EAs was primarily characterized by cell proliferation pathways. Population-specific gene expression was partly driven by population-specific miRNA expression profiles. Drug susceptibility predictions revealed a strong inverse correlation between AA resistance and EA sensitivity to the same panel of drugs. Statistically significant differences in M1 and M2 macrophage infiltration were observed in AAs ( < 0.05); however, expression was similar between both. Comparative transcriptomic profiling revealed clear differences in lung tumor biology between AAs and EAs. Increased participation by AAs in lung cancer clinical trials are needed to integrate, and leverage, transcriptomic differences with other clinical information to maximize therapeutic benefit in both AAs and EAs. .

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Section: Discussionmentioning

confidence: 99%

Comparative Transcriptome Profiling Reveals Coding and Noncoding RNA Differences in NSCLC from African Americans and European Americans

Mitchell

Zingone

Toulabi

et al. 2017

Clinical Cancer Research

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“…55 SCD inhibitors, such as SSI-4, betulinic acid (BetA) and MF-438, have been shown to induce apoptosis in cancer cells through multiple mechanisms including induction of the ER-stress response, modulating mitochondrial dynamics by altering cardiolipin structure, and growth inhibition of cancer stem cells (Table 1). 55,56,[219][220][221] Interestingly, not all cancers display sensitivity to SCD inhibition, as they rely on a compensatory desaturation pathway by utilising FADS2 to generate sapienate from palmitate. 57 In this context, sapienate, instead of palmitoleate generated from SCD, contributes substantially to membrane synthesis in hepatocellular and lung carcinomas.…”

Section: Therapeutically Exploiting Fatty Acid Metabolism In Cancermentioning

confidence: 99%

Reprogramming of fatty acid metabolism in cancer

2019

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A common feature of cancer cells is their ability to rewire their metabolism to sustain the production of ATP and macromolecules needed for cell growth, division and survival. In particular, the importance of altered fatty acid metabolism in cancer has received renewed interest as, aside their principal role as structural components of the membrane matrix, they are important secondary messengers, and can also serve as fuel sources for energy production. In this review, we will examine the mechanisms through which cancer cells rewire their fatty acid metabolism with a focus on four main areas of research. (1) The role of de novo synthesis and exogenous uptake in the cellular pool of fatty acids. (2) The mechanisms through which molecular heterogeneity and oncogenic signal transduction pathways, such as PI3K-AKT-mTOR signalling, regulate fatty acid metabolism. (3) The role of fatty acids as essential mediators of cancer progression and metastasis, through remodelling of the tumour microenvironment. (4) Therapeutic strategies and considerations for successfully targeting fatty acid metabolism in cancer. Further research focusing on the complex interplay between oncogenic signalling and dysregulated fatty acid metabolism holds great promise to uncover novel metabolic vulnerabilities and improve the efficacy of targeted therapies.

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“…BA has potent anticancer activity on many kinds of tumor cells, including colon cancer, skin cancer, prostate cancer, lung cancer, liver cancer and breast cancer cell lines 16–19. However, because of its weak hydrosolubility (0.02 μg/mL) and high lipophilicity, BA has been difficult to study the efficacy in vivo and a pharmaceutical formulation has not yet been available 20,21.…”

Section: Introductionmentioning

confidence: 99%

Enzymatic synthesis and in vitro evaluation of folate-functionalized liposomes

Guo¹,

Xu²,

Liu³

et al. 2017

DDDT

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In this study, folate–poly(ethylene glycol)3400–cholesterol conjugates (FA–PEG–Chol) were enzymatically synthesized in one step and incorporated into liposomes to prepare folate (FA)-functionalized liposomes for targeted drug delivery. The FA-functionalized liposomes loaded with betulinic acid (BA) (FA-L-BA) were prepared by thin lipid film method. The FA-L-BA was characterized by their morphology, particle size, zeta potential, encapsulation efficiency (EE), stability, cell cytotoxicity and cellular uptake. The average size of FA-L-BA was 222±8 nm. The spherical particles exhibited a negative electrical charge of −20.12±1.45 mV and high EE of 91.61%±1.16%. The liposomes were taken up selectively by HepG2 cells. FA-L-BA showed enhanced cytotoxicity (50% inhibitory concentration [IC50] =63.07±2.22 μg/mL) compared to nontargeted control normal liposomes loaded with BA (L-BA; IC50 =93.14±2.19 μg/mL) in HepG2 cells in vitro. In addition, FA-functionalized liposomes loaded with Ir-1 (FA-L-Ir-1) showed significantly higher cellular uptake in HepG2 cells compared to nontargeted control normal liposomes loaded with Ir-1 (L-Ir-1). This novel approach for the liposomes surface modified with FA by a one-step enzymatic amidation was expected to provide potential application as a drug carrier for active targeted delivery to tumor cells.

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Betulinic Acid Kills Colon Cancer Stem Cells

Cited by 39 publications

References 0 publications

Comparative Transcriptome Profiling Reveals Coding and Noncoding RNA Differences in NSCLC from African Americans and European Americans

Comparative Transcriptome Profiling Reveals Coding and Noncoding RNA Differences in NSCLC from African Americans and European Americans

Reprogramming of fatty acid metabolism in cancer

Enzymatic synthesis and in vitro evaluation of folate-functionalized liposomes

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