Nanoencapsulated betulinic acid analogue distinctively improves colorectal carcinoma in vitro and in vivo

Dutta, Debasmita; Paul, Barnali; Mukherjee, Biswajit; Mondal, Laboni; Sen, Suparna; Chowdhury, Chinmay; Debnath, Mita Chatterjee

doi:10.1038/s41598-019-47743-y

Cited by 43 publications

(28 citation statements)

References 58 publications

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“…Table 1 shows the physicochemical properties of JNPs. In terms of encapsulation efficiency and drug loading activities our results are compatible with similar reports in the literature (37)(38)(39).…”

Section: Discussionsupporting

confidence: 92%

Cytotoxic and mutagenic potential of juglone: a comparison of free and nano-encapsulated form

Erişen

Arasoğlu

Mansuroğlu

et al. 2020

Archives of Industrial Hygiene and Toxicology

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Despite its evidenced beneficial herbicidal, antibacterial, antiviral, antifungal, and antioxidant effects, the application of juglone (5-hydroxy-1,4,-naphthoquinone) is limited due to its low water solubility and allelopathic and toxic effects. In recent years, research has aimed to overcome these limitations by increasing its solubility and controlling its release through nanoparticular systems. This is the first study to have synthesised and characterised juglone-loaded polymeric nanoparticles and compared them with free juglone for cytotoxicity in mouse (L929 fibroblasts) and alfalfa cells and for mutagenic potential in Salmonella typhimurium TA98/100. Mouse and plant cells treated with free and nano-encapsulated juglone showed a decrease in cell viability in a dose and time-dependent manner, but this effect was significantly lower with the nano-encapsulated form at lower doses. In the TA98 strain with S9, nano-encapsulated juglone did not exhibit mutagenic effects, unlike the free form. Since all results show that juglone encapsulation with polymeric nanoparticles reduced the toxic and mutagenic effects, it has a promising potential to be applied in medicine, food safety, and agriculture.

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Section: Discussionsupporting

confidence: 92%

Cytotoxic and mutagenic potential of juglone: a comparison of free and nano-encapsulated form

Erişen

Arasoğlu

Mansuroğlu

et al. 2020

Archives of Industrial Hygiene and Toxicology

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“…Moreover, BA may induce cell apoptosis by upregulating the expression of Bax and cleaved caspase-3 and downregulating the protein expression of Bcl-2. BA may inhibit the metastasis of cancer cells, increase the production of reactive oxygen species, and reduce the mitochondrial membrane potential of cancer cells, suggesting that BA induces cancer cell apoptosis through mitochondrial-mediated pathways ( 29 ). However, the molecular mechanism through which BA achieves regulation of metabolic reprogramming and anti-CRC effects has not yet been clearly defined.…”

Section: Discussionmentioning

confidence: 99%

“…Apoptosis induced by in vitro antiproliferative activity was significantly increased by 2c-NP compared with the free drug (2c), and efficient depolarization of the mitochondrial membrane was observed in HT-29 cells upon increased cellular uptake of 2c-NP. Nanoencapsulation of 2c caused an appreciable decrease in cytotoxicity against normal cells in vitro and improvement of therapeutic efficacy in vivo ( 29 ). The present study also demonstrated that BA-NLs can inhibit glucose uptake and lactate secretion by CRC cells and may be involved in the regulation of glycolysis.…”

Section: Discussionmentioning

confidence: 99%

Effects and mechanisms of fatty acid metabolism‑mediated glycolysis regulated by betulinic acid‑loaded nanoliposomes in colorectal cancer

Wang

et al. 2020

Oncol Rep

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Although previous studies have demonstrated that triterpenoids, such as betulinic acid (BA), can inhibit tumor cell growth, their potential targets in colorectal cancer (CRC) metabolism have not been systematically investigated. In the present study, BA-loaded nanoliposomes (BA-NLs) were prepared, and their effects on CRC cell lines were evaluated. The aim of the present study was to determine the anticancer mechanisms of action of BA-NLs in fatty acid metabolism-mediated glycolysis, and investigate the role of key targets, such as acyl-CoA synthetase (ACSL), carnitine palmitoyltransferase (CPT) and acetyl CoA, in promoting glycolysis, which is activated by inducing hexokinase (HK), phosphofructokinase-1 (PFK-1), phosphoenolpyruvate (PEP) and pyruvate kinase (PK) expression. The results demonstrated that BA-NLs significantly suppressed the proliferation and glucose uptake of CRC cells by regulating potential glycolysis and fatty acid metabolism targets and pathways, which forms the basis of the anti-CRC function of BA-NLs. Moreover, the effects of BA-NLs were further validated by demonstrating that the key targets of HK2, PFK-1, PEP and PK isoenzyme M2 (PKM2) in glycolysis, and of ACSL1, CPT1a and PEP in fatty acid metabolism, were blocked by BA-NLs, which play key roles in the inhibition of glycolysis and fatty acid-mediated production of pyruvate and lactate. The results of the present study may provide a deeper understanding supporting the hypothesis that liposomal BA may regulate alternative metabolic pathways implicated in CRC adjuvant therapy.

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“…Betulinic acid promoted the apoptosis of CRC cells and also inhibited the metastasis of cancer cells [468]. Nano-capsulated analogue (2c) with better therapeutic efficacy than parent molecule to colon carcinoma cells has been reported [469].…”

Section: Betulinic Acid (Pentacyclic Triterpenoid)mentioning

confidence: 99%

Alternative Treatments for Cancer Prevention and Cure [Part 1]

Mohiuddin¹

2019

APCT

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Many lay people along with some so called "key opinion leaders" have a common slogan "There's no answer for cancer". Again, mistake delays proper treatment and make situation worse, more often. Compliance is crucial to obtain optimal health outcomes, such as cure or improvement in QoL. Patients may delay treatment or fail to seek care because of high out-of-pocket expenditures. Despite phenomenal development, conventional therapy falls short in cancer management. There are two major hurdles in anticancer drug development: dose-limiting toxic side effects that reduce either drug effectiveness or the QoL of patients and complicated drug development processes that are costly and time consuming. Cancer patients are increasingly seeking out alternative medicine and might be reluctant to disclose its use to their oncology treatment physicians. But there is limited available information on patterns of utilization and efficacy of alternative medicine for patients with cancer. As adjuvant therapy, many traditional medicines shown efficacy against brain, head and neck, skin, breast, liver, pancreas, kidney, bladder, prostate, colon and blood cancers. The literature reviews non-pharmacological interventions used against cancer, published trials, systematic reviews and meta-analyses.

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Nanoencapsulated betulinic acid analogue distinctively improves colorectal carcinoma in vitro and in vivo

Cited by 43 publications

References 58 publications

Cytotoxic and mutagenic potential of juglone: a comparison of free and nano-encapsulated form

Cytotoxic and mutagenic potential of juglone: a comparison of free and nano-encapsulated form

Effects and mechanisms of fatty acid metabolism‑mediated glycolysis regulated by betulinic acid‑loaded nanoliposomes in colorectal cancer

Alternative Treatments for Cancer Prevention and Cure [Part 1]

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