Selective killing of cancer cells by leaf extract of Ashwagandha: Components, activity and pathway analyses

2008 ◽  
Vol 262 (1) ◽  
pp. 37-47 ◽  
Author(s):  
Nashi Widodo ◽  
Yasuomi Takagi ◽  
Bhupal G. Shrestha ◽  
Tetsuro Ishii ◽  
Sunil C. Kaul ◽  
...  
2020 ◽  
Vol 10 ◽  
Author(s):  
Amutha Santhanam ◽  
Naveen Kumar Chandrasekharan ◽  
Rajangam Ilangovan

Background: The occurrence of Cancer results in cellular changes that causes the uncontrolled growth and division of cells. Apoptosis removes cells during development and eliminates the potentially cancerous cells. The bioactive compounds present in the herbal plant shows cytotoxic activity that result in apoptosis. The traditional herbal plants are used world-wide both in allopathy and other traditional ways. Objective: The main objective of this study is to extract the bioactive compound Quercetin from the medicinally significant plant Ocimum sanctum and also to develop nanomedicine as Qu-PEG-NiGs. Materials and Methods: Leaf extract of the medicinally significant plant Ocimum sanctum (O. sanctum) has been used for the synthesis of nickel nanoparticles (NiGs) and extraction of quercetin (Qu). The ethanolic extract of Ocimum sanctum is added to 1 mM Nickel Nitrate (Ni(NO3)2) and stirred for 3 hrs at RT and dried at 60°C for 3hrs and calcinated at 400°C for 2hrs and characterized using Uv-Vis Spectrophotometer, FT-IR, SEM, DLS and Zeta potential. The Quercetin is isolated from Ocimum sanctum leaf extract using the reflux condenser method. The bio-polymer is being PEG-coated over NiGs and Quercetin is loaded into it. The apoptosis activity using MCF-7 cells is performed with Qu-PEG-NiGs. The purity of Quercetin is characterized using HPLC. In order to analyse apoptosis efficiency, MTT assay, Reactive Oxygen Species (ROS), Cell cycle analysis has been performed. Results: The NiGs absorption spectrum gives a peak at 408nm. The FT-IR confirms the presence of particular functional groups shifting from the compound NiGs and then coated with PEG-Qu-NiGs. The SEM images show the size of NiGs ranging from 27.3 nm to 40.4 nm with varied morphology such as hexagonal and other irregular shapes. The presence of Quercetin extracted from the leaf powder is approximately 1.5 mg/g. The ROS results show the Qu-PEG-NiGs induced efficiency of the apoptosis, while the increased concentrations promote ROS and lead to activation of the apoptosis. The cell cycle analysis has shown the cytotoxic effect. Conclusion: PEG-coated nickel nanoparticles can be used as a promising chemotherapeutic agent against MCF7 breast cancer cells. It is the evidence to further studies for evaluating Qu-PEG-NiGs anticancer activity on different types of cancer cells.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Taisei Kanamori ◽  
Natumi Miyazaki ◽  
Shigeki Aoki ◽  
Kousei Ito ◽  
Akihiro Hisaka ◽  
...  

AbstractDespite progress in the use of hyperthermia in clinical practice, the thermosensitivity of cancer cells is poorly understood. In a previous study, we found that sensitivity to hyperthermia varied between ovarian and uterine cancer cell lines. Upon hyperthermia, glycolytic enzymes decreased in hyperthermia-resistant SKOV3 cells. However, the mechanisms of glycolysis inhibition and their relationship with thermoresistance remain to be explored. In this study, metabolomic analysis indicated the downregulation of glycolytic metabolites in SKOV3 cells after hyperthermia. Proteomic and pathway analyses predicted that the ubiquitin pathway was explicitly activated in resistant SKOV3 cells, compared with hyperthermia-sensitive A2780 cells, and STUB1, a ubiquitin ligase, potentially targeted PKM, a glycolytic rate-limiting enzyme. PKM is degraded via ubiquitination upon hyperthermia. Although glycolysis is inactivated by hyperthermia, ATP production is maintained. We observed that oxygen consumption and mitochondrial membrane potential were activated in SKOV3 cells but suppressed in A2780 cells. The activation of mitochondria could compensate for the loss of ATP production due to the suppression of glycolysis by hyperthermia. Although the physiological significance has not yet been elucidated, our results demonstrated that metabolomic adaptation from the Warburg effect to mitochondrial oxidative phosphorylation could contribute to thermoresistance in ovarian and uterine cancer cells.


2021 ◽  
Vol 134 ◽  
pp. 111139
Author(s):  
Reyes Benot-Dominguez ◽  
Maria Grazia Tupone ◽  
Vanessa Castelli ◽  
Michele d’Angelo ◽  
Elisabetta Benedetti ◽  
...  

Lung Cancer ◽  
2012 ◽  
Vol 77 ◽  
pp. S22 ◽  
Author(s):  
M. Dany ◽  
N. Madi ◽  
N. Nemer ◽  
M. Beyrouthy ◽  
S. Abdoun ◽  
...  

Author(s):  
Bui Thi Thanh Duyen ◽  
Vu Manh Hung ◽  
Bui Thanh Tung

Celastrus hindsii Benth et Hook. is known as a herbal medicine for the treatment of cancer. In this study we evaluated the cytotoxic and antioxidant effects of Celastrus hindsii Benth et Hook. leaf extract. Samples of Celastrus hindsii were extracted with 90 % ethanol and subsequently fractionated with n-hexane, ethyl acetate (EtOAc) and n-butanol (n-BuOH) solvents. To evaluate the cytotoxic effect, we performed MTT (3- (4,5 dimethylthiazol-2 - yl) - 2,5 - diphenyltetrazolium) assay on the three cell lines human liver Hep G2 (HB - 8065TM), lung LU-1 (HTB - 57TM), breast MCF-7 (HTB - 22TM).  The antioxidant effect was evaluated by screening DPPH (2,2-diphenyl-1-picryhydrazyl) free radical assay. The results showed that the EtOAc fraction had the strongest cytoxicity effects on liver cancer cells and lung cancer cells with an IC50 value of 33,7 ± 1,5 mg/mL and 13,0 ± 0,5 mg/mL. The BuOH fraction showed a weaker effect on lung cancer cells with IC50 value of 64,0 ± 2,2 mg/mL. The antioxidant results indicated that the EtOAc fraction had the best antioxidant effect with IC50  value of 46,9 ± 2,5 µg/mL. The EtOH total extract also has strong antioxidant activity with IC50 value of 48,5 ± 2,3 µg/mL. Our study showed that Celastrus hindsii leaf extract has the strong cytotoxicity and antioxidant activities. Keywords Celastrus hindsii Benth et Hook., cytotoxicity, MTT, antioxidant, DPPH. References [1] Ministry of health, General oncology. 2009: Vietnam Education Publishing House Limited Company, 9-10.[2] N.V. Tuyen, Pharmaceutical chemistry curriculum, 2014, Science and Technics Publishing House. 222-223.[3] V.V. Chi. Dictionary of Vietnamese medicinal plants. Medical Publishing House 1 (2012).[4] V. Gan, G. Chen, W. Zhang, J. Zhou . Oleanen induces apoptosis of cervical cancer cells by up-regulation of Bim. International Journal of Gynecologic Cancer 22(1) (2012) 38.[5] Y.H. Kuo, L.M.Y. Kuo. Antitumour and anti-AIDS triterpenes from Celastrus hindsii. Phytochemistry 44(7) (1997) 1275.[6] T. Mosmann, Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays 65(1-2) (1983) 55.[7] P. Mahakunakorn, M. Tohda, Y. Murakami, K. Matsumoto, H.J.B. Watanabe, P. Bulletin, Antioxidant and free radical-scavenging activity of Choto-san and its related constituents 27(1) (2004) 38.[8] P.T. Thuong, M.K. Na, N.H. Dang, T.M. Hung, P.T. Ky, T.V. Thanh, et al. Antioxidant activities of Vietnamese medicinal plants 12(1) (2006) 29.[9] X.Q. Hu, W. Han, Z.Z. Han, Q.X. Li, X.K. Xu, P. Fu, et al. A new macrocyclic lactone and a new quinoflavan from Celastrus hindsii. Phytochemistry letters 7 (2014) 169.[10] A.C. Spivey, M. Weston, Woodhead SJCSR. Celastraceae sesquiterpenoids: biological activity and synthesis 31(1) (2002) 43.[11] T.L. Ngoc, Technology. Separation process of rosmarinic acid and their derivatives from Celastrus hindsii benth leaves. Vietnam Journal of Science 54(2C) (2016) 380.[12] F.R. Mowsumi, A. Rahaman, N.C. Sarker, B.K. Choudhury, Hossain SJWJPPS. In vitro relative free radical scavenging effects of Calocybe indica (milky oyster) and Pleurotus djamor (pink oyster). 4(07) (2015).[13] T.D. Viet, T.D. Xuan, T.M. Van, Y. Andriana, R. Rayee, H.D. Tran. Comprehensive Fractionation of Antioxidants and GC-MS and ESI-MS Fingerprints of Celastrus hindsii Leaves. Medicines 6(2) (2019) 64.[14] T.N. Ly, M. Shimoyamada, Yamauchi RJJoa, chemistry f. Isolation and characterization of rosmarinic acid oligomers in Celastrus hindsii Benth leaves and their antioxidative activity 54(11) (2006) 3786.    


2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Bamigboye J. Taiwo ◽  
Temidayo D. Popoola ◽  
Fanie R. van Heerden ◽  
Amos A. Fatokun

ABSTRACT Background The leaf of Anacardium occidentale L. has been a component of many herbal recipes in South-Western Nigeria. The work reported herein, therefore, explored the phytochemical composition of this plant and the potential anti-cancer activity of an isolated chemical constituent. Methods Phytochemical methods (including chromatographic analysis) combined with spectroscopic and spectrometric analyses (IR, HRMS and NMR (1D and 2D)) were used to identify chemical constituents. Cytotoxic effects were determined using the MTT viability assay and bright-field imaging. Induction of oxidative stress was determined using the fluorescence-based 2′,7′-dichlorofluorescein diacetate (DCFDA) assay. Results For the first time in the plant, Compound 1 was isolated from the leaf extract and identified as pentagalloylglucose. Compound 1 was significantly cytotoxic against the cancer cell lines HeLa (human cervical adenocarcinoma cell line) and MRC5-SV2 (human foetal lung cancer cell line), with IC50 of 71.45 and 52.24 μg/ml, respectively. The selectivity index (SI) for Compound 1 was 1.61 (IC50 against the normal human foetal lung fibroblast cell line MRC-5 was 84.33μg/ml), demonstrating better cancer cell-selectivity compared to doxorubicin with a SI of 1.28. The cytotoxic activity of Compound 1 in HeLa cells was also rapid, as shown by its concentration- and time-dependent 3 h and 6 h cytotoxicity profiles, an effect not observed with doxorubicin. Generation of reactive oxygen species at high concentrations of pentagalloylglucose to induce oxidative stress in cancer cells was identified as a mechanistic event that led to or resulted from its cytotoxicity. Conclusions We suggest that pentagalloylglucose is selectively cytotoxic to cancer cells, and at high concentrations could exhibit pro-oxidant effects in those cells, as opposed to its general anti-oxidant effects in cells. Also, the presence of Compound 1 (pentagalloylglucose) in the plant and its cancer cell-selective cytotoxicity provide some rationale for the ethno-medicinal use of the plant’s leaf extract for treating diseases associated with excessive cell proliferation. Further studies are required to dissect the molecular mechanisms and players differentially regulating the biphasic anti-oxidant and pro-oxidant effects of pentagalloylglucose in normal and cancer cells.


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