scholarly journals Lemongrass Extract Possesses Potent Anticancer Activity Against Human Colon Cancers, Inhibits Tumorigenesis, Enhances Efficacy of FOLFOX, and Reduces Its Adverse Effects

2019 ◽  
Vol 18 ◽  
pp. 153473541988915 ◽  
Author(s):  
Ivan Ruvinov ◽  
Christopher Nguyen ◽  
Benjamin Scaria ◽  
Caleb Vegh ◽  
Ola Zaitoon ◽  
...  

Current chemotherapeutics for metastatic colorectal cancers have limited success and are extremely toxic due to nonselective targeting. Some natural extracts have been traditionally taken and have shown anticancer activity. These extracts have multiple phytochemicals that can target different pathways selectively in cancer cells. We have shown previously that lemongrass ( Cymbopogon citratus) extract is effective at inducing cell death in human lymphomas. However, the efficacy of lemongrass extract on human colorectal cancer has not been investigated. Furthermore, its interactions with current chemotherapies for colon cancer is unknown. In this article, we report the anticancer effects of ethanolic lemongrass extract in colorectal cancer models, and importantly, its interactions with FOLFOX and Taxol. Lemongrass extract induced apoptosis in colon cancer cells in a time and dose-dependent manner without harming healthy cells in vitro. Oral administration of lemongrass extract was well tolerated and effective at inhibiting colon cancer xenograft growth in mice. It enhanced the anticancer efficacy of FOLFOX and, interestingly, inhibited FOLFOX-related weight loss in animals given the combination treatment. Furthermore, feeding lemongrass extract to APCmin/+ transgenic mice led to the reduction of intestinal tumors, indicating its preventative potential. Therefore, this natural extract has potential to be developed as a supplemental treatment for colorectal cancer.

Molecules ◽  
2021 ◽  
Vol 26 (15) ◽  
pp. 4417
Author(s):  
Rabin Neupane ◽  
Saloni Malla ◽  
Mariam Sami Abou-Dahech ◽  
Swapnaa Balaji ◽  
Shikha Kumari ◽  
...  

A novel series of 4-anilinoquinazoline analogues, DW (1–10), were evaluated for anticancer efficacy in human breast cancer (BT-20) and human colorectal cancer (CRC) cell lines (HCT116, HT29, and SW620). The compound, DW-8, had the highest anticancer efficacy and selectivity in the colorectal cancer cell lines, HCT116, HT29, and SW620, with IC50 values of 8.50 ± 2.53 µM, 5.80 ± 0.92 µM, and 6.15 ± 0.37 µM, respectively, compared to the non-cancerous colon cell line, CRL1459, with an IC50 of 14.05 ± 0.37 µM. The selectivity index of DW-8 was >2-fold in colon cancer cells incubated with vehicle. We further determined the mechanisms of cell death induced by DW-8 in SW620 CRC cancer cells. DW-8 (10 and 30 µM) induced apoptosis by (1) producing cell cycle arrest at the G2 phase; (2) activating the intrinsic apoptotic pathway, as indicated by the activation of caspase-9 and the executioner caspases-3 and 7; (3) nuclear fragmentation and (4) increasing the levels of reactive oxygen species (ROS). Overall, our results suggest that DW-8 may represent a suitable lead for developing novel compounds to treat CRC.


2015 ◽  
Vol 08 (05) ◽  
pp. 1550027 ◽  
Author(s):  
Ricky W. K. Wu ◽  
Ellie S. M. Chu ◽  
Zheng Huang ◽  
Malini C. Olivo ◽  
David C. W. Ip ◽  
...  

Photodynamic therapy (PDT) is a novel therapeutic approach for combating various cancers. PDT involves the administration of a photosensitizer which generates singlet oxygen after light activation. FosPegⓇ is the liposomal formulation of mTHPC. In this in vitro study, the photodynamic efficacy of FosPegⓇ on a human colon cancer cell line (HT29) was investigated via studying the cellular uptake of FosPegⓇ, FosPegⓇ PDT mediated photocytotoxicity and the cell death mechanism were triggered. FosPegⓇ PDT demonstrated its antitumor effect in a drug and light dose-dependent manner in HT-29 cells. Lethal dose (LD50) was achieved with 0.4 μg/mL of drug and 3 J/cm-2 of light dose. FosPegⓇ PDT triggered apoptotic cell death via activating caspase cascade and regulating cell cycle progression. In conclusion, FosPegⓇ-PDT is an effective measure to combat human colon cancer cells.


2021 ◽  
Vol 22 (15) ◽  
pp. 8117
Author(s):  
Nunzia D’Onofrio ◽  
Elisa Martino ◽  
Luigi Mele ◽  
Antonino Colloca ◽  
Martina Maione ◽  
...  

Understanding the mechanisms of colorectal cancer progression is crucial in the setting of strategies for its prevention. δ-Valerobetaine (δVB) is an emerging dietary metabolite showing cytotoxic activity in colon cancer cells via autophagy and apoptosis. Here, we aimed to deepen current knowledge on the mechanism of δVB-induced colon cancer cell death by investigating the apoptotic cascade in colorectal adenocarcinoma SW480 and SW620 cells and evaluating the molecular players of mitochondrial dysfunction. Results indicated that δVB reduced cell viability in a time-dependent manner, reaching IC50 after 72 h of incubation with δVB 1.5 mM, and caused a G2/M cell cycle arrest with upregulation of cyclin A and cyclin B protein levels. The increased apoptotic cell rate occurred via caspase-3 activation with a concomitant loss in mitochondrial membrane potential and SIRT3 downregulation. Functional studies indicated that δVB activated mitochondrial apoptosis through PINK1/Parkin pathways, as upregulation of PINK1, Parkin, and LC3B protein levels was observed (p < 0.0001). Together, these findings support a critical role of PINK1/Parkin-mediated mitophagy in mitochondrial dysfunction and apoptosis induced by δVB in SW480 and SW620 colon cancer cells.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Helena de Castro e Gloria ◽  
Laura Jesuíno Nogueira ◽  
Patrícia Bencke Grudzinski ◽  
Paola Victória da Costa Ghignatti ◽  
Temenouga Nikolova Guecheva ◽  
...  

Abstract Background The advances in colorectal cancer (CRC) treatment include the identification of deficiencies in Mismatch Repair (MMR) pathway to predict the benefit of adjuvant 5-fluorouracil (5-FU) and oxaliplatin for stage II CRC and immunotherapy. Defective MMR contributes to chemoresistance in CRC. A growing body of evidence supports the role of Poly-(ADP-ribose) polymerase (PARP) inhibitors, such as Olaparib, in the treatment of different subsets of cancer beyond the tumors with homologous recombination deficiencies. In this work we evaluated the effect of Olaparib on 5-FU cytotoxicity in MMR-deficient and proficient CRC cells and the mechanisms involved. Methods Human colon cancer cell lines, proficient (HT29) and deficient (HCT116) in MMR, were treated with 5-FU and Olaparib. Cytotoxicity was assessed by MTT and clonogenic assays, apoptosis induction and cell cycle progression by flow cytometry, DNA damage by comet assay. Adhesion and transwell migration assays were also performed. Results Our results showed enhancement of the 5-FU citotoxicity by Olaparib in MMR-deficient HCT116 colon cancer cells. Moreover, the combined treatment with Olaparib and 5-FU induced G2/M arrest, apoptosis and polyploidy in these cells. In MMR proficient HT29 cells, the Olaparib alone reduced clonogenic survival, induced DNA damage accumulation and decreased the adhesion and migration capacities. Conclusion Our results suggest benefits of Olaparib inclusion in CRC treatment, as combination with 5-FU for MMR deficient CRC and as monotherapy for MMR proficient CRC. Thus, combined therapy with Olaparib could be a strategy to overcome 5-FU chemotherapeutic resistance in MMR-deficient CRC.


2021 ◽  
Vol 10 (1) ◽  
pp. 572-585
Author(s):  
Darren Yi Sern Low ◽  
Camille Keisha Mahendra ◽  
Janarthanan Supramaniam ◽  
Loh Teng Hern Tan ◽  
Learn Han Lee ◽  
...  

Abstract In this study, ultrasonically driven biosynthesis of zinc oxide nanoparticles (ZnO NPs) using Swietenia macrophylla seed ethyl acetate fraction (SMEAF) has been reported. X-ray powder diffraction (XRD) and Fourier-transform infrared spectroscopy (FTIR) analyses confirmed the presence of a pure hexagonal wurtzite structure of ZnO. Field emission scanning electron microscope images revealed the formation of uniquely identifiable uniform rice-shaped biologically synthesized ZnOSMEAF particles. The particle sizes of the biosynthesized NPs ranged from 262 to 311 nm. The underlying mechanisms for the biosynthesis of ZnOSMEAF under ultrasound have been proposed based on FTIR and XRD results. The anticancer activity of the as-prepared ZnOSMEAF was investigated against HCT-116 human colon cancer cell lines via methyl thiazolyl tetrazolium assay. ZnOSMEAF exhibited significant anticancer activity against colon cancer cells with higher potency than ZnO particles prepared using the chemical method and SMEAF alone. Exposure of HCT-116 colon cancer cells to ZnOSMEAF promoted a remarkable reduction in cell viability in all the tested concentrations. This study suggests that green sonochemically induced ZnO NPs using medicinal plant extract could be a potential anticancer agent for biomedical applications.


2012 ◽  
Vol 23 ◽  
pp. iv85-iv86
Author(s):  
Ying Lin ◽  
Yuan-yuan Fang ◽  
Hong Su ◽  
Zhou Hui-Min ◽  
Qi-Kui Chen

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Wei-Jan Huang ◽  
Yu-Chih Liang ◽  
Shuang-En Chuang ◽  
Li-Ling Chi ◽  
Chi-Yun Lee ◽  
...  

HDAC inhibitors (HDACis) have been developed as promising anticancer agents in recent years. In this study, we synthesized and characterized a novel HDACi, termed NBM-HD-1. This agent was derived from the semisynthesis of propolin G, isolated from Taiwanese green propolis (TGP), and was shown to be a potent suppressor of tumor cell growth in human breast cancer cells (MCF-7 and MDA-MB-231) and rat glioma cells (C6), with an IC50ranging from 8.5 to 10.3 μM. Western blot demonstrated that levels of p21(Waf1/Cip1), gelsolin, Ac-histone 4, and Ac-tubulin markedly increased after treatment of cancer cells with NBM-HD-1. After NBM-HD-1 treatment for 1–4 h, p-PTEN and p-AKT levels were markedly decreased. Furthermore, we also found the anticancer activities of NBM-HD-1 in regulating cell cycle regulators. Treatment with NBM-HD-1,p21(Waf1/Cip1)gene expression had markedly increased whilecyclin B1andD1gene expressions had markedly decreased. On the other hand, we found that NBM-HD-1 increased the expressions of tumor-suppressor genep53in a dose-dependent manner. Finally, we showed that NBM-HD-1 exhibited potent antitumor activity in a xenograft model. In conclusion, this study demonstrated that this compound, NBM-HD-1, is a novel and potent HDACi with anticancer activityin vitroandin vivo.


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