Anticancer Activity of Leonurus sibiricus L.: Possible Involvement of Intrinsic Apoptotic Pathway

A new dinuclear cyclic gold(I) complex [Au2(DCyPA)2](PF6)2, 1 based on bis[2-(dicyclohexylphosphano)ethyl]amine (DCyPA) has been synthesized and characterized by elemental analysis, IR and NMR spectroscopies, and X-ray crystallography. In the dinuclear...

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Activation of the intrinsic-apoptotic pathway in LNCaP prostate cancer cells by genistein- topotecan combination treatments

Functional Foods in Health and Disease ◽

10.31989/ffhd.v3i3.64 ◽

2013 ◽

Vol 3 (3) ◽

pp. 66 ◽

Cited By ~ 2

Author(s):

Vanessa Hörmann ◽

Sivanesan Dhandayuthapani ◽

James Kumi-Diaka ◽

Appu Rathinavelu

Keyword(s):

Prostate Cancer ◽

Cell Death ◽

Cancer Cells ◽

Apoptotic Cell ◽

Treatment Options ◽

Attractive Alternative ◽

Intrinsic Apoptotic Pathway ◽

Prostate Cancer Cells ◽

Apoptotic Pathway ◽

Combination Treatments

Background: Prostate cancer is the second most common cancer in American men. The development of alternative preventative and/or treatment options utilizing a combination of phytochemicals and chemotherapeutic drugs could be an attractive alternative compared to conventional carcinoma treatments. Genistein isoflavone is the primary dietary phytochemical found in soy and has demonstrated anti-tumor activities in LNCaP prostate cancer cells. Topotecan Hydrochloride (Hycamtin) is an FDA-approved chemotherapy for secondary treatment of lung, ovarian and cervical cancers. The purpose of this study was to detail the potential activation of the intrinsic apoptotic pathway in LNCaP prostate cancer cells through genistein-topotecan combination treatments. Methods: LNCaP cells were cultured in complete RPMI medium in a monolayer (70-80% confluency) at 37ºC and 5% CO2. Treatment consisted of single and combination groups of genistein and topotecan for 24 hours. The treated cells were assayed for i) growth inhibition through trypan blue exclusion assay and microphotography, ii) classification of cellular death through acridine/ ethidium bromide fluorescent staining, and iii) activation of the intrinsic apoptotic pathway through Jc-1: mitochondrial membrane potential assay, cytochrome c release and Bcl-2 protein expression.Results: The overall data indicated that genistein-topotecan combination was significantly more efficacious in reducing the prostate carcinoma’s viability compared to the single treatment options. In all treatment groups, cell death occurred primarily through the activation of the intrinsic apoptotic pathway.Conclusion: The combination of topotecan and genistein has the potential to lead to treatment options with equal therapeutic efficiency as traditional chemo- and radiation therapies, but lower cell cytotoxicity and fewer side effects in patients. Key words: topotecan; genistein; intrinsic apoptotic cell death

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Bis (Isothiocyanatomethyl) Benzene, A Plant Derived Anti-Neoplastic Compound: Purified from Moringa Oleifera Leaf Extract

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520619666190206164137 ◽

2019 ◽

Vol 19 (5) ◽

pp. 677-686 ◽

Cited By ~ 2

Author(s):

Samrat Paul ◽

Piyali Basak ◽

Namrata Maity ◽

Chayan Guha ◽

Nandan Kumar Jana

Keyword(s):

Anticancer Activity ◽

Leaf Extract ◽

Moringa Oleifera ◽

Folk Medicine ◽

Drug Formulation ◽

Indigenous Species ◽

Cancer Cell Growth ◽

Apoptotic Pathway ◽

Dimeric Form ◽

Mcf 7

Background: Moringa oleifera lam, commonly known as “Sajina”, is an indigenous species to India. In our folk medicine, it is used for the treatment of Canker (cancer). The Moringa oleifera leaf extract contains many phyto-compounds, with some being anti-neoplastic in nature. Objective: Our preliminary study showed that the leaf extract significantly kills cancer cells compared to normal cells. On searching for the new phyto-compound, Bis-isothiocyanatomethyl) benzene was purified and isolated. Methods: The sequential process of fractional distillation, column chromatography, followed by TLC and HPLC is performed for purification. Every fraction from each step was tested on HeLa cell line for evaluating the presence of the phyto-compound. Results and Conclusion: FTIR peak analysis of a single phyto-compound shows the presence of thiocyanate group, aromatic carbon group. 1H & 13C NMR peak analysis along with High-resolution mass spectroscopy (HRMS) calculation confirm the chemical structure with IUPAC name [Bis (Isothiocyanatomethyl) benzene]. Previously, Isothiocyanatomethyl- benzene solely or in conjugation with sugar molecule has been reported, but its dimeric form in nature hasnot yet been published anywhere. It shows anticancer activity by retarding cancer cell growth & inhibits carcinogenesis on HeLa, MCF-7, and MDA-MB-231 cell lines by caspase 3 apoptotic pathway and showed comparatively less cytotoxicity to PBMC cell. It shows anticancer activity almost the same as the market available drug Cis-Platin. Therefore, further extrapolating its activity with different concentrations may result in its use as a drug formulation for the treatment of cancer.

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Role of testosterone in the intrinsic apoptotic pathway of skeletal muscle

Bone ◽

10.1016/j.bone.2011.03.740 ◽

2011 ◽

Vol 48 (6) ◽

pp. S288

Author(s):

L. Pronsato ◽

R. Boland ◽

L. Milanesi

Keyword(s):

Skeletal Muscle ◽

Intrinsic Apoptotic Pathway ◽

Apoptotic Pathway

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Mitochondrial MDM4 (MDMX): An unpredicted role in the p53-mediated intrinsic apoptotic pathway

Cell Cycle ◽

10.4161/cc.8.23.10089 ◽

2009 ◽

Vol 8 (23) ◽

pp. 3854-3859 ◽

Cited By ~ 25

Author(s):

Francesca Mancini ◽

Fabiola Moretti

Keyword(s):

Intrinsic Apoptotic Pathway ◽

Apoptotic Pathway

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Protective effects of a Ganoderma atrum polysaccharide against acrylamide induced oxidative damage via a mitochondria mediated intrinsic apoptotic pathway in IEC-6 cells

Food & Function ◽

10.1039/c7fo01619k ◽

2018 ◽

Vol 9 (2) ◽

pp. 1133-1143 ◽

Cited By ~ 12

Author(s):

Guoyong Jiang ◽

Lulu Zhang ◽

Hui Wang ◽

Qian Chen ◽

Xiaolin Wu ◽

...

Keyword(s):

Oxidative Damage ◽

Natural Compound ◽

Protective Effects ◽

Intrinsic Apoptotic Pathway ◽

Apoptotic Pathway ◽

Apoptotic Damage

PSG-1-F2 is an effective and natural compound that could prevent ACR-induced apoptotic damage via a ROS triggered mitochondria associated pathway.

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7-hydroxyfrullanolide, isolated from Sphaeranthus indicus, inhibits colorectal cancer cell growth by p53-dependent and -independent mechanism

Carcinogenesis ◽

10.1093/carcin/bgy176 ◽

2018 ◽

Vol 40 (6) ◽

pp. 791-804

Author(s):

Praveen Pandey ◽

Deepika Singh ◽

Mohammad Hasanain ◽

Raghib Ashraf ◽

Mayank Maheshwari ◽

...

Keyword(s):

Cell Growth ◽

Anticancer Activity ◽

Cancer Cell ◽

Molecular Mechanisms ◽

Target Genes ◽

Cancer Cell Growth ◽

Apoptotic Pathway ◽

Syngeneic Mouse Model ◽

Sphaeranthus Indicus

Abstract Sphaeranthus indicus Linn. is commonly used in Indian traditional medicine for management of multiple pathological conditions. However, there are limited studies on anticancer activity of this plant and its underlying molecular mechanisms. Here, we isolated an active constituent, 7-hydroxyfrullanolide (7-HF), from the flowers of this plant, which showed promising chemotherapeutic potential. The compound was more effective in inhibiting in vitro proliferation of colon cancers cells through G2/M phase arrest than other cancer cell lines that were used in this study. Consistent with in vitro data, 7-HF caused substantial regression of tumour volume in a syngeneic mouse model of colon cancer. The molecule triggered extrinsic apoptotic pathway, which was evident as upregulation of DR4 and DR5 expression as well as induction of their downstream effector molecules (FADD, Caspase-8). Concurrent activation of intrinsic pathway was demonstrated with loss of ΔΨm to release pro-apoptotic cytochrome c from mitochondria and activation of downstream caspase cascades (Caspase -9, -3). Loss of p53 resulted in decreased sensitivity of cells towards pro-apoptotic effect of 7-HF with increased number of viable cells indicating p53-dependent arrest of cancer cell growth. This notion was further supported with 7-HF-mediated elevation of endogenous p53 level, decreased expression of MDM2 and transcriptional upregulation of p53 target genes in apoptotic pathway. However, 7-HF was equally effective in preventing progression of HCT116 p53+/+ and p53−/− cell derived xenografts in nude mice, which suggests that differences in p53 status may not influence its in vivo efficacy. Taken together, our results support 7-HF as a potential chemotherapeutic agent and provided a new mechanistic insight into its anticancer activity.

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