Celastrol Enhances the Anti-Liver Cancer Activity of Sorafenib

Zhang, Rui; Zhi, Cheng; Wu, Shusheng; Xu, Jun; Kong, Lingchun; Pei, Wei

doi:10.12659/msm.914060

Cited by 27 publications

(17 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To overcome these limitations, one strategy is to combine new agents from natural compounds with standard therapy to reduce adverse effects [ 4 ]. For instance, celastrol, extracted from vine tree roots, enhanced the tumor suppression and apoptosis induction effects of sorafenib [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Brassinin Inhibits Proliferation in Human Liver Cancer Cells via Mitochondrial Dysfunction

Hong

Ham

Song

et al. 2021

Cells

View full text Add to dashboard Cite

Brassinin is a phytochemical derived from Chinese cabbage, a cruciferous vegetable. Brassinin has shown anticancer effects on prostate and colon cancer cells, among others. However, its mechanisms and effects on hepatocellular carcinoma (HCC) have not been elucidated yet. Our results confirmed that brassinin exerted antiproliferative effects by reducing proliferating cell nuclear antigen (PCNA) activity, a proliferation indicator and inducing cell cycle arrest in human HCC (Huh7 and Hep3B) cells. Brassinin also increased mitochondrial Ca2+ levels and depolarized the mitochondrial membrane in both Huh7 and Hep3B cells. Moreover, brassinin generated high amounts of reactive oxygen species (ROS) in both cell lines. The ROS scavenger N-acetyl-L-cysteine (NAC) inhibited this brassinin-induced ROS production. Brassinin also regulated the AKT and mitogen-activated protein kinases (MAPK) signaling pathways in Huh7 and Hep3B cells. Furthermore, co-administering brassinin and pharmacological inhibitors for JNK, ERK1/2 and P38 decreased cell proliferation in both HCC cell lines more than the pharmacological inhibitors alone. Collectively, our results demonstrated that brassinin exerts antiproliferative effects via mitochondrial dysfunction and MAPK pathway regulation on HCC cells.

show abstract

Section: Introductionmentioning

confidence: 99%

Brassinin Inhibits Proliferation in Human Liver Cancer Cells via Mitochondrial Dysfunction

Hong

Ham

Song

et al. 2021

Cells

View full text Add to dashboard Cite

show abstract

“…Autocrine VEGF production is one of the key molecular factors to acquire resistance to VEGFR inhibitors in HCC cells [ 30 ]. A recent report has demonstrated that treatment with sorafenib increased VEGF production in human hepatoma cells [ 31 ]. In line with this, our results revealed the autocrine production of VEGF-A in Huh-7 cells under lenvatinib treatment.…”

Section: Discussionmentioning

confidence: 99%

The Angiotensin II Receptor Blocker Losartan Sensitizes Human Liver Cancer Cells to Lenvatinib-Mediated Cytostatic and Angiostatic Effects

Takagi

Kaji

Nishimura

et al. 2021

Cells

View full text Add to dashboard Cite

Molecular targeted therapy with lenvatinib is commonly offered to advanced hepatocellular carcinoma (HCC) patients, although it is often interrupted by adverse effects which require a reduction in the initial dose. Thus, an alternative lenvatinib-based therapy to compensate for dose reduction is anticipated. This study aimed to assess the effect of combination of low-dose of lenvatinib and the angiotensin-II (AT-II) receptor blocker losartan on human HCC cell growth. In vitro studies found that losartan suppressed the proliferation by inducing G1 arrest and caused apoptosis as indicated by the cleavage of caspase-3 in AT-II-stimulated HCC cell lines (Huh-7, HLE, and JHH-6). Losartan attenuated the AT-II-stimulated production of vascular endothelial growth factor-A (VEGF-A) and interleukin-8 and suppressed lenvatinib-mediated autocrine VEGF-A production in HCC cells. Moreover, it directly inhibited VEGF-mediated endothelial cell growth. Notably, the combination of lenvatinib and losartan augmented the cytostatic and angiostatic effects of the former at a low-dose, reaching those achieved with a conventional dose. Correspondingly, a HCC tumor xenograft assay showed that the oral administration of losartan combined with lenvatinib reduced the subcutaneous tumor burden and intratumor vascularization in BALB/c nude mice. These findings support that this regimen could be a viable option for patients intolerant to standard lenvatinib dosage.

show abstract

“…Celastrol alleviated chronic obstructive pulmonary disease in the lungs of mice ( Shi et al, 2018 ). It has an anti-inflammatory pathway through the suppression of nuclear factor kappa B (NF-κB) signalling ( Zhang et al, 2019 ). In a study conducted on MERS-CoV and SARS-CoV infections, the inflammatory response mediated by NF-κB pathway was regulated by transmembrane serine protease 2 (TMPRSS2) levels within the airway in a TMPRSS2 knockout murine model ( Iwata-Yoshikawa et al, 2019 ; Nabavi et al, 2020 ), suggesting that the inhibition of TMPRSS2 may exert a dual effect on COVID-19, limiting viral entry by reducing the cleavage of the spike protein in ACE2 receptor mediated viral entry ( Hoffmann et al, 2020 ; Nabavi et al, 2020 ).…”

Section: Natural Products As Possible Management/treatment Options Fomentioning

confidence: 99%

Natural product remedies for COVID-19: A focus on safety

Omokhua-Uyi

Staden

2021

South African Journal of Botany

View full text Add to dashboard Cite

Infection by the novel coronavirus SARS-CoV-2 causing the coronavirus disease (COVID-19), is currently a global pandemic with nearly two million deaths to date. Though a number of vaccines have recently been approved against the virus, availability remains a big challenge, and also acceptance by most people has become a big debate. This review discusses possible/ proposed natural product remedies and some major conventional treatment options used to manage the infection and, safety concerns on the use of unproven or unapproved health products against COVID-19. An extensive literature review indicated that the influx of unproven and unapproved health products in the global market are on the rise, leading to various forms of self- medication. To this effect, there have been warnings by the United States Food and Drug Administration and the World Health Organisation against the use of such products. Conventional drugs such as remdesivir, chloroquine/hydroxychloroquine and dexamethasone are the major proposed drugs that are currently undergoing clinical trials for the management of this disease. Efforts are being made globally in the search for possible therapeutics which may be the best way to eradicating this disease. Some countries have approved the use of natural products in the management of COVID-19, despite little or no clinical evidence on their efficacy and safety. Natural products may hold a great potential in the fight against COVID-19 but without detailed clinical trials, their potency against the virus and their safe use cannot be established. To attain this goal, extensive research followed by clinical studies are needed. Collaborative efforts between researchers, clinicians, governments and traditional medicinal practitioners in the search and development of safe and effective therapeutics from natural products for the treatment of COVID-19 could be a potential option.

show abstract

Celastrol Enhances the Anti-Liver Cancer Activity of Sorafenib

Cited by 27 publications

References 28 publications

Brassinin Inhibits Proliferation in Human Liver Cancer Cells via Mitochondrial Dysfunction

Brassinin Inhibits Proliferation in Human Liver Cancer Cells via Mitochondrial Dysfunction

The Angiotensin II Receptor Blocker Losartan Sensitizes Human Liver Cancer Cells to Lenvatinib-Mediated Cytostatic and Angiostatic Effects

Natural product remedies for COVID-19: A focus on safety

Contact Info

Product

Resources

About