Sensitivities of Uterine Adenocarcinoma, Mixed Mullerian Tumor (MMT) and Sarcoma Cell Lines to Chemotherapeutic Agents and a Flex-Het Drug

Hyde, Johnny; Benbrook, Doris M.

doi:10.3844/ajptsp.2006.83.86

Cited by 4 publications

(4 citation statements)

References 13 publications

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“…Apart from DR ligands, SHetA2 has also shown its chemosensitizing effects against cisplatin-resistant ovarian cancer through p53-independent pathways [6,56]. However, such enhancement of sensitivities was not observed in resistant uterine cancer cell lines for a number of chemotherapeutics in combination with SHetA2 treatment (Figure 8) [57]. ↑ Bip/GRP78, IRE1α, ATF4, XBP1 ER stress [49] ↑ DR-5 Cell death [55] ↑ CHOP Cell death [49] ↓ IKK Cell survival [55] ↓ NF-kB Cell survival [50] ↓ c-FLIP Antiapoptotic [50] Cell cycle pathways ↓ Cyclin D1 G 1 arrest [11] ↓ AP-1 Cell-cycle progression [62] Differentiation induction pathways ↑ E-Cadherin Differentiation [7] ↑ MUC1 Differentiation [44] Antiangiogenic pathways ↑ Thrombospondin (TSP-4) Antiangiogenic [12] ↓ Thymidine Phosphorylase (TP) Angiogenic [12] ↓ VEGF Angiogenic [12] Signal transduction pathways Table 4.…”

Section: Extrinsic Pathway (Death Receptor Pathway)mentioning

confidence: 99%

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SHetA2, a New Cancer-Preventive Drug Candidate

Liu¹,

Zhou²,

Lo³

et al. 2016

Anti-Cancer Drugs - Nature, Synthesis and Cell

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SHetA2 (NSC 721689) is a novel synthetic flexible heteroarotinoid that has promising cancer-preventive activity, and has exhibited growth inhibition on 60 cancer cell lines in vitro, along with ovarian, lung, and kidney cancers in vivo. It binds and interferes with the function of a molecular chaperone, mortalin, leading to mitochondrial swelling and mitophagy that induce apoptosis in cancer cells without harming normal cells. It showed minimal toxicity in preclinical studies and thus is now in Phase-0 clinical trial. This chapter summarizes its evolution, synthesis, structure-activity relationship, mechanism of action, pharmacokinetics, and potential clinical applications in last 12 years. It also provides insights into designing more potent and safer SHetA2 analogs for future cancer-preventive drug development.

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Section: Extrinsic Pathway (Death Receptor Pathway)mentioning

confidence: 99%

“…SHetA2 decreased survival of all three cell lines, but did not increase sensitivities of cell lines to chemotherapeutic drugs. [57] Lung cancer (NSCLC) Increased sensitivity to TRAIL-induced apoptosis through modulation of c-FLIP and upregulation of DR5. Inhibits growth, triggers ER stress.…”

Section: Findings Referencesmentioning

confidence: 99%

SHetA2, a New Cancer-Preventive Drug Candidate

Liu¹,

Zhou²,

Lo³

et al. 2016

Anti-Cancer Drugs - Nature, Synthesis and Cell

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“…The Immune Defence actions of V. amygdalina include all those actions it carries out in defence and protection of the various organs of an organism. The action of identifying cancerous tissues of an organism as a "non-self" and as detrimental to the life of the individual is in itself a non-specific immune response (Hyde and Benbrook, 2006;Suzuki et al 2005). The inhibition and destruction of carcinoma by V. amygdalina extract are thus clearly immune defence actions as they rid the body of unwanted malignant cells.…”

Section: Introductionmentioning

confidence: 99%

Mechanisms of Anti-Cancer Effects of <i>Vernonia amygdalina</i> Leaf Extract

Anastasia¹

2011

American Journal of Pharmacology and Toxicology

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Problem statement: Vernonia amygdalina (V. amygdalina) has been shown to have cancer cell inhibition and cytotoxic effects. Approach: This study discusses the multi-faceted and multilinked mechanisms by which cancer tissue inhibition and destruction is achieved by V. amygdalina leaf extract and powder (subsequently called V. amygdalina Extract). Cancer cell inhibition by V. amygdalina is suggested to occur through inhibition of sterol 14-α-demethylase, a microsomal P450dependent enzyme system) of the membrane of the cancer cell. Inhibition of this enzyme impairs the biosynthesis of ergosterol for the cytoplasmic membrane. Results: This impairment of the synthesis of ergosterol disrupts the close packing of acyl chains of phospholipids and impairs the function of some membrane-bound enzyme systems like ATPase and enzymes of electron-transport system of the cancer cells. V. amygdalina extract inhibits sterol 14-α-demethylase by acting on β 3 adrenergic receptors of the cancer cell membranes as a primary ligand in Gi (inhibitory) receptors on cancer β 3 lipid cell membrane receptors and mitochondrial ATP energy generation system receptors. Conclusion: By effecting β-oxidation of fatty acids and lipids in cell membranes and cell mitochondrial energy (ATP) generation systems, the V. amygdalina extract uncouples the mitochondrial energy (ATP generation) systems of the cancer cells and cell membranes resulting in the cancer cells being burnt out (consumed) by the extract (when V. amygdalina extract is cytotoxic to the cancer cells) or its functioning being inhibited (when V. amygdalina extract is only inhibitory to the cancer cells.

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“…This fact suggests that there may be some basic facts about health/illness and drug treatment 0f disease that still need to be understood. As nature itself is a great teacher, this study examined the patterns of disease infectivity on the body of living things to draw conclusions on the common sites of disease infectivity and their relationship to other parts of the same organ or organism (Abu-Jayyab, 2009;Barret and Blanc, 2009;Gottschalk et al, 2005;Guruswamy and Benbrook, 2006;Hyde and Benbrook, 2006;Kumar, 2009;Lam et al, 2010;Liakou et al, 2007;Lu et al, 2010;Lundholm, 1985;Memo et al, 1985;Menard et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Distribution, Arrangement and Interconnectedness of Cell Surface Receptor sites in the body of an Organism

Utoh-Nedosa

Anastasia

2011

OnLine Journal of Biological Sciences

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Cell surface receptors have been identified as the sites of disease infectivity in living organisms in a previous study. Drugs used for the treatment or cure of infections have to eliminate infections through attacking infective organisms at the cell surface receptors to which the infective organisms are attached. Problem statement: The present study examines a wide sample of living things to get more information on the relationship of one cell surface receptor to other cell surface receptors in the body of an organism. Approach: The arrangement of cell surface receptors on the external covering of a few samples of fruits, leaves, stems, dry wood of a plant; wall gecko and some parts of the human body, were examined and photographed. Transverse and/or Longitudinal sections of soursop fruit and sycamore fruit were also examined and photographed. The five different coverings of the fleshy part of a coconut were also photographed. The photographs were studied to note the relationship of disease infection attached to cell surface receptors on the external surface of an organ to disease infection on the innermost covering of the same organ. Results: The results of the study showed that all living things had ubiquitous distribution of cell surface receptors which are usually observable with the unaided eye as dots or spots on the external covering of an organ, tissue or cell. The dots or receptor sites of cell surface receptors in the study are arranged in lines which were perpendicular, oblique, transverse or arranged in any other lineal geometrical form. The lineally arranged cell surface receptors were noted to be connected by grooves, channels or pipes which joined other receptor channels or intersected with them. Smaller cell surface receptor channels emptied into bigger channels or continued as small sized channels that ran side by side in a connective tissue bundle. These connective tissue bundles that carried many independent small-sized cell surface receptor channels joined up to form larger bundles that ran the whole length of the organism. In this way, the cell surface receptors in a locality were interconnect through bigger receptor channel highways to cell surface receptors in other remote parts of the body. This arrangement was illustrated by the sycamore fruit and the soursop fruit. The results of the study also showed that cell surface receptors have functional zonal units with other cell surface receptors which were delimited by cell surface receptor channels. The zoning system of cell surface receptors meant that an infection or a drug treatment of an infection would affect all the cell surface receptors of the same functional unit to the same degree. The cell surface receptor site was raised up when a disease infection at the site was being attacked by a body defence substance of an exogenous drug. Some cell surface receptors were damaged or obliterated or damaged by disease. Examination of different layers of the coconut fruit coverings showed that cell surface receptors traverse all exte...

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Sensitivities of Uterine Adenocarcinoma, Mixed Mullerian Tumor (MMT) and Sarcoma Cell Lines to Chemotherapeutic Agents and a Flex-Het Drug

Cited by 4 publications

References 13 publications

SHetA2, a New Cancer-Preventive Drug Candidate

SHetA2, a New Cancer-Preventive Drug Candidate

Mechanisms of Anti-Cancer Effects of <i>Vernonia amygdalina</i> Leaf Extract

Distribution, Arrangement and Interconnectedness of Cell Surface Receptor sites in the body of an Organism

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