scholarly journals Impact of Sodium Dichloroacetate Alone and in Combination Therapies on Lung Tumor Growth and Metastasis

2021 ◽  
Vol 22 (22) ◽  
pp. 12553
Author(s):  
Aya Al-Azawi ◽  
Shahrazad Sulaiman ◽  
Kholoud Arafat ◽  
Javed Yasin ◽  
Abderrahim Nemmar ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Nude Mice ◽  
Colony Growth ◽  
Metabolic Reprogramming ◽  
Cellular Migration ◽  
Pyruvate Dehydrogenase Kinase ◽  
Axillary Lymph ◽  
Anti Cancer

Metabolic reprogramming has been recognized as an essential emerging cancer hallmark. Dichloroacetate (DCA), an inhibitor of pyruvate dehydrogenase kinase (PDK), has been reported to have anti-cancer effects by reversing tumor-associated glycolysis. This study was performed to explore the anti-cancer potential of DCA in lung cancer alone and in combination with chemo- and targeted therapies using two non-small cell lung cancer (NSCLC) cell lines, namely, A549 and LNM35. DCA markedly caused a concentration- and time-dependent decrease in the viability and colony growth of A549 and LNM35 cells in vitro. DCA also reduced the growth of tumor xenografts in both a chick embryo chorioallantoic membrane and nude mice models in vivo. Furthermore, DCA decreased the angiogenic capacity of human umbilical vein endothelial cells in vitro. On the other hand, DCA did not inhibit the in vitro cellular migration and invasion and the in vivo incidence and growth of axillary lymph nodes metastases in nude mice. Treatment with DCA did not show any toxicity in chick embryos and nude mice. Finally, we demonstrated that DCA significantly enhanced the anti-cancer effect of cisplatin in LNM35. In addition, the combination of DCA with gefitinib or erlotinib leads to additive effects on the inhibition of LNM35 colony growth after seven days of treatment and to synergistic effects on the inhibition of A549 colony growth after 14 days of treatment. Collectively, this study demonstrates that DCA is a safe and promising therapeutic agent for lung cancer.

scholarly journals ABCG2-overexpressing H460/MX20 cell xenografts in athymic nude mice maintained original biochemical and cytological characteristics

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Wei Zhang ◽  
Zhen Chen ◽  
Likun Chen ◽  
Fang Wang ◽  
Furong Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Cycle ◽  
Nude Mice ◽  
Large Cell ◽  
Athymic Nude Mice ◽  
H460 Cell ◽  
Large Cell Lung Cancer ◽  
Cytological Characteristics

Abstract H460/MX20 are derived from large cell lung cancer H460 cell line and then transformed into ABCG2-overexpressing cells by mitoxantrone’s induction, which are widely used in study of multidrug resistance (MDR) in vitro. To establish and spread the model of H460/MX20 cell xenografts, we investigated whether cell biological characteristics and the MDR phenotype were maintained in vivo model. Our results demonstrated that the cell proliferation, cell cycle, and ABCG2 expression level in xH460/MX20 cells isolated from H460/MX20 cell xenografts were similar to H460/MX20 cells in vitro. Importantly, xH460/MX20 cells exhibited high levels of resistance to ABCG2 substrates such as mitoxantrone and topotecan as H460/MX20 cells did. Furthermore, lapatinib, the inhibitor of ABCG2, potently reversed mitoxantrone- and topotecan-resistance of xH460/MX20 cells. Taken together, these results suggest that H460/MX20 cell xenografts in athymic nude mice still retain their original cytological characteristics and MDR phenotype. Thus, the H460/MX20 cell xenografts model could serve as a sound model in vivo for study on reversal MDR.

scholarly journals Anti-cancer effects of baicalein in non-small cell lung cancer in-vitro and in-vivo

BMC Cancer ◽  
2016 ◽  
Vol 16 (1) ◽  
Author(s):  
Mary-Clare Cathcart ◽  
Zivile Useckaite ◽  
Clive Drakeford ◽  
Vikki Semik ◽  
Joanne Lysaght ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Anti Cancer

Bradykinin-related compounds as new drugs for cancer and inflammation

2002 ◽  
Vol 80 (4) ◽  
pp. 275-280 ◽  
Author(s):  
John M Stewart ◽  
Lajos Gera ◽  
Daniel C Chan ◽  
Paul A Bunn Jr. ◽  
Eunice J York ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Lung Cancer ◽  
Tumor Growth ◽  
Small Cell Lung Cancer ◽  
Nude Mice ◽  
Small Cell ◽  
Small Cell Lung ◽  
Related Compounds

Bradykinin (BK) (Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg) is an important growth factor for small-cell lung cancer (SCLC) and prostate cancer (PC). These cancers have cells of neuroendocrine origin and express receptors for a variety of neuropeptides. BK receptors are expressed on almost all lung cancer cell lines and on many PC cells. Our very potent BK antagonist B9430 (D-Arg-Arg-Pro-Hyp-Gly-Igl-Ser-D-Igl-Oic-Arg) (Hyp, trans-4-hydroxy-L-proline; Igl, α-2-indanylglycine; Oic, octahydroindole-2-carboxylic acid) is a candidate anti-inflammatory drug but does not inhibit growth of SCLC or PC. When B9430 is dimerized by N-terminal cross-linking with a suberimide linker, the product B9870 is a potent growth inhibitor for SCLC both in vitro and in vivo in athymic nude mice. Daily i.p. injection at 5 mg·kg–1·day–1 beginning on day 8 after SCLC SHP-77 cell implantation gave 65% inhibition of tumor growth. B9870 stimulates apoptosis in SCLC by a novel "biased agonist" action. We have also developed new small mimetic antagonists. BKM-570 (F5C-OC2Y-Atmp) (F5C, pentafluorocinnamic acid; OC2Y, O-2,6-dichlorobenzyl tyrosine; Atmp, 4-amino-2,2,6,6-tetramethylpiperidine) is very potent for inhibition of SHP-77 growth in nude mice. When injected daily i.p. at 5 mg·kg–1, M-570 gave 90% suppression of tumor growth. M-570 is more potent than the well-known anticancer drug cisPlatin (60% inhibition) or the recently developed SU5416 (40% inhibition) in this model. M-570 also showed activity against various other cancer cell lines in vitro (SCLC, non-SCLC, lung, prostate, colon, cervix) and inhibited growth of prostate cell line PC3 in nude mice. M-570 and related compounds evidently act in vivo through pathways other than BK receptors. These compounds have clinical potential for treatment of human lung and prostate cancers.Key words: bradykinin antagonists, cancer, inflammation, prostate cancer, small cell lung cancer.

Evaluation of Anti-Tumor Potential of Lactobacillus acidophilus ATCC4356 Culture Supernatants in MCF-7 Breast Cancer

2020 ◽  
Vol 21 ◽  
Author(s):  
Ramazan Behzadi ◽  
Ahmad Hormati ◽  
Karim Eivaziatashbeik ◽  
Sajjad Ahmadpour ◽  
Fatemeh Khodadust ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Nude Mice ◽  
Control Group ◽  
Bacterial Strains ◽  
Anti Cancer ◽  
99Mtc Mibi ◽  
Culture Supernatants ◽  
Mcf 7

Background: Anti-cancer activity of some lactic acid bacterial strains is well documented in several literatures. Lactobacillus strains have received considerable attention as a beneficial microbiota. The aim of this study is to evaluate the effects of anti-tumor activities of L. acidophilus ATCC4356 culture supernatants on the MCF-7 human breast cancer cells. Materials and methods: Anti-cancer effect of 24h and 48h culture supernatants at various concentrations (1.25, 2.5, 5, 10 and 20 µg/ml) were determined by various in vitro and in vivo assays including MTT, tumor volume measurement as well as 99mTc-MIBI biodistribution in MCF-7 tumor bearing nude mice and histopathology test. For evaluation of the related mechanism of action, quantitative PCR was conducted. Results: The 48h culture supernatants at 10 and 20 µg/ml exhibited significant in vitro inhibition of MCF-7 cell proliferation. However, this inhibition was not observed for HUVEC human endothelial normal cells. Q-PCR indicated that treatment by the supernatant led to a significant downregulation of VEGFR ( ̴ 0.009 fold) and Bcl-2 ( ̴ 0.5 fold) and upregulation of p53 ( ̴ 1.3 fold). In vivo study using MCF-7 xenograft mouse models demonstrated reduction in tumor weight and volume by both 24h and 48h supernatants (10 µg/ml and 20 µg/ml) after 15 days. According to the 99mTc-MIBI biodistribution result, treatment of MCF-7 bearing nude mice with both 24h and 48h supernatant (20 µg/ml) led to significant decrease in tumor uptake compared with the control group. Conclusion: These results suggest that the culture supernatants of L. acidophilus ATCC4356 at suitable concentrations can be considered as a good alternative nutraceutical with promising therapeutic indexes for breast cancer.

scholarly journals Oxymatrine Attenuates Tumor Growth and Deactivates STAT5 Signaling in a Lung Cancer Xenograft Model

Cancers ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 49 ◽  
Author(s):  
Young Yun Jung ◽  
Muthu K. Shanmugam ◽  
Acharan S. Narula ◽  
Chulwon Kim ◽  
Jong Hyun Lee ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Mouse Model ◽  
A549 Cells ◽  
Xenograft Model ◽  
Signaling Cascade ◽  
Anticancer Effects ◽  
Anti Cancer

Oxymatrine (OMT) is a major alkaloid found in radix Sophorae flavescentis extract and has been reported to exhibit various pharmacological activities. We elucidated the detailed molecular mechanism(s) underlying the therapeutic actions of OMT in non-small cell lung cancer (NSCLC) cells and a xenograft mouse model. Because the STAT5 signaling cascade has a significant role in regulating cell proliferation and survival in tumor cells, we hypothesized that OMT may disrupt this signaling cascade to exert its anticancer effects. We found that OMT can inhibit the constitutive activation of STAT5 by suppressing the activation of JAK1/2 and c-Src, nuclear localization, as well as STAT5 binding to DNA in A549 cells and abrogated IL-6-induced STAT5 phosphorylation in H1299 cells. We also report that a sub-optimal concentration of OMT when used in combination with a low dose of paclitaxel produced significant anti-cancer effects by inhibiting cell proliferation and causing substantial apoptosis. In a preclinical lung cancer mouse model, OMT when used in combination with paclitaxel produced a significant reduction in tumor volume. These results suggest that OMT in combination with paclitaxel can cause an attenuation of lung cancer growth both in vitro and in vivo.

scholarly journals Potent anti-cancer activity of Alnus nitida against lung cancer cells; in vitro and in vivo studies

2019 ◽  
Vol 110 ◽  
pp. 254-264 ◽  
Author(s):  
Moniba Sajid ◽  
Chao Yan ◽  
Dawei Li ◽  
Siva Bharath Merugu ◽  
Hema Negi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Lung Cancer Cells ◽  
In Vivo Studies ◽  
Anti Cancer ◽  
Cancer Activity

scholarly journals Mechanistic Understanding of Curcumin’s Therapeutic Effects in Lung Cancer

Nutrients ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 2989 ◽  
Author(s):  
Wan Nur Baitty Wan Mohd Tajuddin ◽  
Nordin H. Lajis ◽  
Faridah Abas ◽  
Iekhsan Othman ◽  
Rakesh Naidu
Keyword(s):  
Lung Cancer ◽  
Curcuma Longa ◽  
Survival Rates ◽  
In Vivo Studies ◽  
Therapeutic Effects ◽  
Epigenetic Alterations ◽  
Anti Cancer ◽  
Lung Cancer Therapy

Lung cancer is among the most common cancers with a high mortality rate worldwide. Despite the significant advances in diagnostic and therapeutic approaches, lung cancer prognoses and survival rates remain poor due to late diagnosis, drug resistance, and adverse effects. Therefore, new intervention therapies, such as the use of natural compounds with decreased toxicities, have been considered in lung cancer therapy. Curcumin, a natural occurring polyphenol derived from turmeric (Curcuma longa) has been studied extensively in recent years for its therapeutic effects. It has been shown that curcumin demonstrates anti-cancer effects in lung cancer through various mechanisms, including inhibition of cell proliferation, invasion, and metastasis, induction of apoptosis, epigenetic alterations, and regulation of microRNA expression. Several in vitro and in vivo studies have shown that these mechanisms are modulated by multiple molecular targets such as STAT3, EGFR, FOXO3a, TGF-β, eIF2α, COX-2, Bcl-2, PI3KAkt/mTOR, ROS, Fas/FasL, Cdc42, E-cadherin, MMPs, and adiponectin. In addition, limitations, strategies to overcome curcumin bioavailability, and potential side effects as well as clinical trials were also reviewed.

Combined Treatment with JFKD and Gefitinib Overcomes Drug Resistance in Non-Small Cell Lung Cancer

2020 ◽  
Vol 21 ◽  
Author(s):  
Xiaoming Huang ◽  
Jingchun Sun ◽  
Jianli Sun
Keyword(s):  
Lung Cancer ◽  
Drug Resistance ◽  
Combined Treatment ◽  
Small Cell ◽  
Small Cell Lung ◽  
In Vivo Experiments ◽  
Anti Cancer ◽  
Putative Mechanism

Background: Gefitinib is an important drug used to treat non-small cell lung cancer (NSCLC) with EGFR activating mutations, but drug resistance restricts its clinical application. In this present study, combined Jin Fu Kang Decoction (JFKD) and gefitinib showed specific cytotoxicity to gefitinib-resistant cancer cells (PC-9/gef). Objective: The aim of this study was to decipher the molecular mechanism of the JFKD on drug resistance when used together with Gefitinib and to find the contributing bio-active substance(s) in JFKD based on the putative mechanism. Methods: To investigate the combined effect of gefitinib and JFKD, in vitro experiments were conducted on the established gefitinib-resistant PC-9 subclone, while in vivo experiments were conducted on the Balbc nude mice with PC-9/gef xenografts. Western blot was used to evaluate the protein expression, and ultra-performance liquid chromatography (UPLC) coupled with quadrupole time-of-flight mass spectrometry (MS) was used to detect the bio-active compounds of JFKD. Results: The expression of the PTEN-relevant protein p-EGFR, p-Akt in vitro was inhibited more when combined JKFD and gefitinibwere used, whereas the activities of PDCD4 and PTEN were increased; remarkably, in vivo experiments showed enhanced tumor growth inhibition when treated with this combination . Due to this combination, the effect on the gefitinib-resistant cell line, one of the JFKD-induced anti-cancer mechanisms, was found. To link the putative mechanism and the anti-cancer compounds in JFKD, 14 saponins and flavonoids were detected. Conclusion: The present results suggested that a promising TCM-participated therapy can be established by the putative mechanism of the combined treatment in resistant NSCLC and screening the contributing bio-active substance(s) in JFKD is meaningful on new TCM formula discovery.

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