Natural Compounds As Modulators of Non-apoptotic Cell Death in Cancer Cells

Guamán-Ortiz, Luis Miguel; Orellana, María Isabel Ramirez; Ratovitski, Edward A.

doi:10.2174/1389202917666160803150639

Cited by 37 publications

(27 citation statements)

References 335 publications

(575 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Molecular networks are important to the aforementioned processes and are linked to maintain a balance. Treatment strategy for cancer relies on anticancer therapy to cause tumor-specific cell death without destroying normal neighboring cells [ 6 ]. Autophagy and apoptosis are cellular mechanisms that regulate organelles and protein turnover in cells, and of cells inside organisms, respectively.…”

Section: Introductionmentioning

confidence: 99%

The In Vitro and In Vivo Anticancer Properties of Chalcone Flavokawain B through Induction of ROS-Mediated Apoptotic and Autophagic Cell Death in Human Melanoma Cells

Hseu

Chiang

Gowrisankar

et al. 2020

Cancers

View full text Add to dashboard Cite

Melanoma is the most prevalent type of skin cancer with high mortality rates. This study demonstrates the in vitro and in vivo anticancer properties of chalcone flavokawain B (FKB) induced ROS-mediated apoptosis and autophagy in human melanoma (human epithelial melanoma cell line A375 and/or human skin lymph node derived melanoma cell line A2058) cells. Cell viability was calculated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and the expression patterns of various apoptosis, autophagy-associated proteins were determined by Western blot methods. Annexin V was detected by flow cytometry, whereas acidic vesicular organelles (AVOs) and intracellular ROS levels were measured by fluorescence microscopy. The in vivo anticancer properties of FKB were evaluated by xenografting the A375 cells into nude mice. The results convey that FKB inhibited cell viability, B-Raf proto-oncogene, serine/threonine kinase (BRAF)/extracellular signal-regulated kinase (ERK) expression in human melanoma cells. Caspase-3 activation, poly (ADP-ribose) polymerase (PARP) cleavage pathway, and Bcl2 associated X (Bax)/B-cell lymphoma 2 (Bcl-2) dysregulation were involved in the execution of apoptosis. Moreover, FKB-induced autophagy was observed through increased microtubule-associated protein 1A/1B-light chain 3B (LC3-II) accumulation and AVOs formation, which was also associated with an increase in sequestosome 1 (SQSTM1/p62), decreased protein kinase B (AKT)/mammalian target of rapamycin (mTOR) expressions, and dysregulated Beclin-1/Bcl-2 levels. Autophagy inhibitors [3-methyladenine (3-MA)/chloroquine (CQ)] and LC3 silencing suppressed FKB-induced apoptosis by decreasing caspase-3 in melanoma cells. The antioxidant N-acetylcysteine (NAC) diminished FKB-induced apoptotic and autophagic cell death. However, the inhibition of apoptosis decreased FKB-induced autophagy (LC3-I/II). The in vivo study confirmed that FKB inhibited melanoma growth in A375-xenografted nude mice. This study concluded that FKB is critically associated with the execution and generation of ROS-modulated apoptotic and autophagic cell death of melanoma cells. FKB also repressed tumor growth in xenografted nude mice. Therefore, flavokawain B might be a potential anti-tumor agent in human melanoma treatment.

show abstract

Section: Introductionmentioning

confidence: 99%

The In Vitro and In Vivo Anticancer Properties of Chalcone Flavokawain B through Induction of ROS-Mediated Apoptotic and Autophagic Cell Death in Human Melanoma Cells

Hseu

Chiang

Gowrisankar

et al. 2020

Cancers

View full text Add to dashboard Cite

show abstract

“…There is as yet no biochemical assay for paraptosis. The associated morphology can be recognized by the appearance of multiple cytoplasmic vacuoles (17)(18)(19)(20)(21)(22). These are not autophagosomes, that is, they have single membranes and their formation may be antagonized by brief exposure to agents that impair protein synthesis, for example, actinomycin D or cycloheximide (17).…”

Section: Introductionmentioning

confidence: 99%

Apoptosis, Paraptosis and Autophagy: Death and Survival Pathways Associated with Photodynamic Therapy

Kessel

2018

Photochem & Photobiology

157

130

View full text Add to dashboard Cite

The ability of photosensitizing agents to create photodamage at specific subcellular sites has proved useful for characterizing pathway(s) to cell death and for selecting optimal targets for anti-tumor efficacy. Both apoptosis and autophagy can occur after photodamage directed at mitochondria, lysosomes or the ER, with the balance often a determinant of overall efficacy. A combination of lysosomal + mitochondrial targets is associated with enhanced efficacy. More recently, ER photodamage was found to evoke a mainly unexplored mode of photokilling that involves extensive cytoplasmic vacuole formation but does not represent autophagy. This has been termed "paraptosis" and appears to be a reaction to the appearance of misfolded ER proteins. This report is designed to summarize current knowledge relating to death pathways and update information relating to paraptosis as a PDT response.

show abstract

“…Remarkably, it is possible that autophagy is playing a double role in the SW613-B3 cell line. It is well known that the autophagy mechanism is also active in tumor cell lines and has a role in survival [22,34]; as observed in the clonogenic assay, the SW613-B3 cell line is able to recover after treatment at the IC 50 dose (Figure 1(b)). Figure 4.…”

Section: Gnsbm Extract Induces Autophagymentioning

confidence: 85%

Cytotoxic Property of Grias neuberthii Extract on Human Colon Cancer Cells: A Crucial Role of Autophagy

Guamán-Ortiz

Romero-Benavides

Suárez

et al. 2020

Evidence-Based Complementary and Alternative Medicine

View full text Add to dashboard Cite

Traditional herbal medicine has become an important alternative in the treatment of various cancer types, including colon cancer, which represents one of the main health problems around the world. Therefore, the search for new therapies to counteract this disease is very active. Grias neuberthii is an endemic plant located in the Ecuadorian Amazon region, which has been used in traditional medicine for its pharmacological properties, including its ability to inhibit tumor cell growth, although scientific studies are limited. We have analyzed the effect of this plant on two colon carcinoma cell lines, that is, RKO (normal p53) and SW613-B3 (mutated p53) cells. Among several extracts obtained from various parts of G. neuberthii plant, we identified the extract with the greatest cytotoxic potential, derived from the stem bark. The cytotoxic effect was similar on both cell lines, thus indicating that it is independent of the status of p53. However, significant differences were observed after the analysis of colony formation, with RKO cells being more sensitive than SW613-B3. No evidence for apoptotic markers was recorded; nevertheless, both cell lines showed signs of autophagy after the treatment, including increased Beclin-1 and LC3-II and decreased p62. Finally, three chemical compounds, possibly responsible for the effect observed in both cell lines, were identified: lupeol (1), 3′-O-methyl ellagic acid 4-O-β-D-rhamnopyranoside (2), and 19-α-hydroxy-asiatic acid monoglucoside (3).

show abstract

Natural Compounds As Modulators of Non-apoptotic Cell Death in Cancer Cells

Cited by 37 publications

References 335 publications

The In Vitro and In Vivo Anticancer Properties of Chalcone Flavokawain B through Induction of ROS-Mediated Apoptotic and Autophagic Cell Death in Human Melanoma Cells

The In Vitro and In Vivo Anticancer Properties of Chalcone Flavokawain B through Induction of ROS-Mediated Apoptotic and Autophagic Cell Death in Human Melanoma Cells

Apoptosis, Paraptosis and Autophagy: Death and Survival Pathways Associated with Photodynamic Therapy

Cytotoxic Property of Grias neuberthii Extract on Human Colon Cancer Cells: A Crucial Role of Autophagy

Contact Info

Product

Resources

About