Elucidation of Anticancer Mode of action of Betulinic acid-Cisplatin Conjugates on Lung cancer A549 cells In vitro

Author(s):  
Kranthi Vanchanagiri ◽  
◽  
Thomas Müller ◽  
Reinhard Paschke ◽  
◽  
...  
2020 ◽  
Vol 59 (1) ◽  
pp. 11-20
Author(s):  
Cong Fang ◽  
Yahui Liu ◽  
Lanying Chen ◽  
Yingying Luo ◽  
Yaru Cui ◽  
...  
Keyword(s):  

Nanomaterials ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 152
Author(s):  
Iulia Pinzaru ◽  
Cristian Sarau ◽  
Dorina Coricovac ◽  
Iasmina Marcovici ◽  
Crinela Utescu ◽  
...  

Betulinic acid (BA), a natural compound with various health benefits including selective antitumor activity, has a limited applicability in vivo due to its poor water solubility and bioavailability. Thus, this study focused on obtaining a BA nano-sized formulation with improved solubility and enhanced antitumor activity using silver nanocolloids (SilCo and PEG_SilCo) as drug carriers. The synthesis was performed using a chemical method and the physicochemical characterization was achieved applying UV-Vis absorption, transmission electron microscopy (TEM), Raman and photon correlation spectroscopy (PCS). The biological evaluation was conducted on two in vitro experimental models—hepatocellular carcinoma (HepG2) and lung cancer (A549) cell lines. The physicochemical characterization showed the following results: an average hydrodynamic diameter of 32 nm for SilCo_BA and 71 nm for PEG_SilCo_BA, a spherical shape, and a loading capacity of 54.1% for SilCo_BA and 61.9% for PEG_SilCo_BA, respectively. The in vitro assessment revealed a cell type- and time-dependent cytotoxic effect characterized by a decrease in cell viability as follows: (i) SilCo_BA (66.44%) < PEG_SilCo_BA (72.05%) < BA_DMSO (75.30%) in HepG2 cells, and (ii) SilCo_BA (75.28%) < PEG_SilCo_BA (86.80%) < BA_DMSO (87.99%) in A549 cells. The novel silver nanocolloids loaded with BA induced an augmented anticancer effect as compared to BA alone.


2021 ◽  
Author(s):  
Dan Wang ◽  
Tianshou Cao ◽  
Wanyu Li ◽  
Li Li ◽  
Qunfa Huang ◽  
...  

Abstract Small cell lung cancer (SCLC) accounts for 13% ~ 15% of lung cancer. It is a subtype with high malignancy and poor prognosis. Almost all patients with SCLC will inevitably have drug resistance and tumor recurrence, which has become an urgent problem in the treatment of SCLC. Nuclear-targeted drug delivery system, which enables intra-nuclear release of anticancer drugs, is expected to address this challenge. In this study, based on transactivator of transcription (TAT)’s active transport property to the nucleus, we developed a high-efficiency nucleus-targeted co-delivery vector that delivers genes and drugs directly into the nucleus of A549 cells. The system is based on a poly-(N-ε-carbobenzyloxy-L-lysine) (PZLL) and dendritic polyamidoamine (PAMAM) block copolymer (PZLL-D3) with TAT modified on the surface of carrier. In vitro studies showed that DOX and p53 could can be effectively transported to the nucleus and kill the cancer cells. Thus, such deliver system would bypass the drug resistance and tumor recurrence problem.


2020 ◽  
Vol 52 (9) ◽  
pp. 1007-1015
Author(s):  
Zhe Zhang ◽  
Li Nong ◽  
Menglei Chen ◽  
Xiaoli Gu ◽  
Weiwei Zhao ◽  
...  

Abstract Vasculogenic mimicry (VM) refers to a new tubular network of the blood supply system with abundant extracellular matrix. VM is similar to capillaries but does not involve endothelial cells. As a traditional herbal medicine commonly used in China, baicalein possesses anti-inflammatory and lipoxygenase activities. However, the effects of baicalein on the process of VM formation in non-small cell lung cancer (NSCLC) and the underlying mechanisms have remained poorly understood. In this study, baicalein was found to inhibit the viability and motility of A549 cells and induced the breakage of the cytoskeletal actin filament network. In addition, baicalein significantly decreased the formation of VM and downregulated the expressions of VM-associated factors, such as VE-cadherin, EphA2, MMP14, MMP2, MMP9, PI3K and LAMC2, similar to the effects of ROCK inhibitors. Indeed, baicalein inhibited RhoA/ROCK expression in vitro and in vivo, suggesting the underlying mechanisms of reduced VM formation. Collectively, baicalein suppressed the formation of VM in NSCLC by targeting the RhoA/ROCK signaling pathway, indicating that baicalein might serve as an emerging drug for NSCLC.


Nanomedicine ◽  
2020 ◽  
Vol 15 (1) ◽  
pp. 41-54 ◽  
Author(s):  
Xin Jin ◽  
Qing Yang ◽  
Ning Cai ◽  
Zhenhai Zhang

Aim: Lung cancer has a very high incidence rate, and thus, there is an urgent need for novel and effective therapies. Materials & methods: In this study, we proposed a potential treatment option by combining four natural products in liposome systems. Results: In vitro studies indicated that the combination of betulinic acid, parthenolide, honokiol and ginsenoside Rh2 exhibited a synergistic action. When these four natural products were loaded into liposome systems, we observed an increased effect. The relative action was also observed in vivo. The cisplatin group presented obvious kidney damage, whereas both cocktail therapy and cocktail liposome therapy were safer. Conclusion: Therefore, we propose cocktail liposome systems may provide a more efficient and safer treatment for lung cancer.


2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
XinGang Lu ◽  
Liu Yang ◽  
ChengHua Lu ◽  
ZhenYu Xu ◽  
HongFu Qiu ◽  
...  

Nowadays, chemotherapy is still the main effective treatment for cancer. Herb prescriptions containingPogostemon cablin Benth(also known as “Guang-Huo-Xiang”) have been widely used in Chinese medicine today. In our research, we found that patchouli alcohol, a compound isolated from the oil ofPogostemon cablin Benth, exerted antitumor ability against human lung cancer A549 cells ability bothin vitroandin vivo. MTT assay was used to assess cell viability. Hoechst 33342 staining and TUNEL cover glass staining provided the visual evidence of apoptosis. Caspase activity measurement showed that patchouli alcohol activated caspase 9 and caspase 3 of mitochondria-mediated apoptosis. Consistently, patchouli alcohol inhibited the xenograft tumorin vivo. Further investigation of the underlying molecular mechanism showed that MAPK and EGFR pathway might contribute to the antitumor effect of patchouli alcohol. Our study proved that patchouli alcohol might be able to serve as a novel antitumor compound in the clinical treatment of lung cancer.


2002 ◽  
Vol 30 (02n03) ◽  
pp. 307-314 ◽  
Author(s):  
Hui-Chiu Chang ◽  
Wen-Chun Hung ◽  
Ming-Shyan Huang ◽  
Hseng-Kuang Hsu

Recent study indicated that the components of Toona sinensis Roemor have potent anti-inflammatory and analgesic effects. These components have also been reported to inhibit the growth of boils in vivo. In this study, we investigated the effect of crude extract from the leaves of Toona sinensis Roemor on the proliferation of A549 lung cancer cells. We found that the extract effectively blocked cell cycle progression by inhibiting the expression of cyclin D1 and E in A549 cells. Additionally, incubation of the extract led to activation of caspase-3-like proteases and apoptotic cell death. Conversely, the extract did not show any significant cytotoxic effect on primarily cultured human foreskin fibroblasts or MRC-5 human lung fibroblasts. Therefore, antiproliferative action of the extract is specific for tumor cells. Our results suggest that the components of Toona sinensis Roemor have potent anticancer effects in vitro and identification of the useful components in the extract may lead to the development of a novel class of anticancer drugs.


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