Plant lectins in cancer therapeutics: Targeting apoptosis and autophagy-dependent cell death

Bhutia, Sujit K.; Panda, Prashanta Kumar; Sinha, Niharika; Praharaj, Prakash Priyadarshi; Bhol, Chandra Sekhar; Panigrahi, Debasna Pritimanjari; Mahapatra, Kewal Kumar; Saha, Suparna; Patra, Srimanta; Mishra, Soumya Ranjan; Behera, Bishnu Prasad; Patil, Shankargouda; Maiti, Tapas K.

doi:10.1016/j.phrs.2019.04.001

Cited by 93 publications

(60 citation statements)

References 120 publications

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“…In this sense, when p53 is phosphorylated in serine 46, it induces signaling pathways triggering apoptosis by stopping the cell cycle [37,43,44]. Our results suggest that p53 mutations in HT-29 cells do not affect the phosphorylation in ser46 and TBLF treatment increases the p-p53(ser46) level at 8 h. Similar results have been observed in various studies for lectin-mediated cell death induction pathways [27,[45][46][47][48]. Some other lectins affect the p53-mediated apoptosis pathway [28,49,50].…”

Section: Discussionsupporting

confidence: 88%

Tepary Bean (Phaseolus acutifolius) Lectins Induce Apoptosis and Cell Arrest in G0/G1 by P53(Ser46) Phosphorylation in Colon Cancer Cells

et al. 2020

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A Tepary bean lectin fraction (TBLF) has been studied because it exhibits differential cytotoxic and anticancer effects on colon cancer. The present work focuses on the evaluation of the apoptotic mechanism of action on colon cancer cells. Initially, lethal concentrations (LC50) were obtained for the three studied cell lines (HT-29, RKO and SW-480). HT-29 showed the highest LC50, 10 and 100 times higher than that of RKO and SW-480 cells, respectively. Apoptosis was evaluated by flow cytometry, where HT-29 cells showed the highest levels of early and total apoptosis, caspases activity was confirmed and necrosis was discarded. The effect on cell cycle arrest was shown in the G0/G1 phase. Specific apoptosis-related gene expression was determined, where an increase in p53 and a decrease in Bcl-2 were observed. Expression of p53 gene showed the maximum level at 8 h with an important decrease at 12 and 24 h, also the phosphorylated p53(ser46) increased at 8 h. Our results show that TBLF induces apoptosis in colon cancer cells by p-p53(ser46) involvement. Further studies will focus on studying the specific signal transduction pathway.

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Section: Discussionsupporting

confidence: 88%

Tepary Bean (Phaseolus acutifolius) Lectins Induce Apoptosis and Cell Arrest in G0/G1 by P53(Ser46) Phosphorylation in Colon Cancer Cells

et al. 2020

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“…Recent studies also show that ACD is involved in some tumor therapy. For instance, plant lectins targets both apoptosis and autophagy dependent cell death in cancer therapeutics [36]. A novel triazole NMK-T-057 induces ACD in breast cancer cells by inhibiting γ-secretase-mediated activation of Notch-signaling [37].…”

Section: Discussionmentioning

confidence: 99%

Phosphoinositide specific phospholipase Cγ1 inhibition-driven autophagy caused cell death in human lung adenocarcinoma A549 cells in vivo and in vitro

Lü¹,

Fu²,

Chen³

et al. 2020

Int. J. Biol. Sci.

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Our previous studies indicated that phosphoinositide specific phospholipase Cγ1 (PLCγ1) was involved in autophagy induction in colon and hepatic carcinoma cells. However, whether and how PLCγ1 regulation in human lung adenocarcinoma is linked to autophagy remains unclear. Here, we assessed the protein expression of PLCγ1 in human lung adenocarcinoma tissue using immunohistochemistry assay and the relationship between PLCG1 and autophagy in The Cancer Genome Atlas Network (TCGA) using Spearman correlation analysis and GSEA software. Furthermore, the interaction between PLCγ1 and autophagy-related signal molecules was investigated in human lung adenocarcinoma A549 cells treated with different inhibitors or transduction with lentivirus-mediated PLCγ1 gene short-hairpin RNA (shRNA) vectors using MTT, clonogenicity, Transwell migration, RT-PCR, Caspase-3, mitochondrial transmembrane potential, and western blotting assays, as well as transmission electron microscope technique. Additionally, the effect of shRNA/PLCγ1 alone or combined with autophagic activator Lithium Chloride (LiCl) on tumor growth and metastasis was measured using immunohistochemistry and assays in A549 xenograft nude mouse model. The results showed that increased PLCγ1 expression occurred frequently in human lung adenocarcinoma tissue with higher grades of T in TNM staging classification. PLCγ1 significantly enriched in autophagic process and regulation, which negatively regulating autophagy was enriched in higher expression of PLCγ1. PLCγ1 inhibition partially reduced cell proliferation and migration of A549 cells, with an increased autophagic flux involving alterations of AMPKα, mTOR, and ERK levels. However, PLCγ1 inhibition-driven autophagy led to cell death without depending on Caspase-3 and RIP1. Additionally, the abrogation of PLCγ1 signaling by shRNA and combination with autophagic activator LiCl could efficaciously suppress tumor growth and metastasis in A549 xenograft nude mice, in combination with a decrease in P62 level. These findings collectively suggest that reduction of cell proliferation and migration by PLCγ1 inhibition could be partially attributed to PLCγ1 inhibition-driven autophagic cell death (ACD). It highlights the potential role of a combination between targeting PLCγ1 and autophagy pathway in anti-tumor therapy, which may be an efficacious new strategy to overcome the autophagy addition of tumor and acquired resistance to current therapy.

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“…Several studies have shown that plant and animal lectins exert different biological activities. These compounds inhibit bacterial [18] and fungal growth [19], and have immunomodulatory properties [20,21]. On cancer cell lines, they exhibit antiproliferative properties [20,22], promote apoptosis and autophagy, and block angiogenesis [20,22].…”

Section: Introductionmentioning

confidence: 99%

“…These compounds inhibit bacterial [18] and fungal growth [19], and have immunomodulatory properties [20,21]. On cancer cell lines, they exhibit antiproliferative properties [20,22], promote apoptosis and autophagy, and block angiogenesis [20,22]. Moreover, their ability to bind to carbohydrates could make them useful for the detection of subtle modifications of carbohydrate composition, which appears during cancer transformation [23].…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, their ability to bind to carbohydrates could make them useful for the detection of subtle modifications of carbohydrate composition, which appears during cancer transformation [23]. However, although anticancer activity of terrestrial lectins has been summarized in several reviews [20,24,25], to our knowledge no comprehensive report highlighting uniquely the antineoplastic activity of marine lectins has been written.…”

Section: Introductionmentioning

confidence: 99%

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Antitumor Potential of Marine and Freshwater Lectins

et al. 2019

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Often, even the most effective antineoplastic drugs currently used in clinic do not efficiently allow complete healing due to the related toxicity. The reason for the toxicity lies in the lack of selectivity for cancer cells of the vast majority of anticancer agents. Thus, the need for new potent anticancer compounds characterized by a better toxicological profile is compelling. Lectins belong to a particular class of non-immunogenic glycoproteins and have the characteristics to selectively bind specific sugar sequences on the surface of cells. This property is exploited to exclusively bind cancer cells and exert antitumor activity through the induction of different forms of regulated cell death and the inhibition of cancer cell proliferation. Thanks to the extraordinary biodiversity, marine environments represent a unique source of active natural compounds with anticancer potential. Several marine and freshwater organisms, ranging from the simplest alga to the most complex vertebrate, are amazingly enriched in these proteins. Remarkably, all studies gathered in this review show the impressive anticancer effect of each studied marine lectin combined with irrelevant toxicity in vitro and in vivo and pave the way to design clinical trials to assess the real antineoplastic potential of these promising proteins. It provides a concise and precise description of the experimental results, their interpretation as well as the experimental conclusions that can be drawn.

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Plant lectins in cancer therapeutics: Targeting apoptosis and autophagy-dependent cell death

Cited by 93 publications

References 120 publications

Tepary Bean (Phaseolus acutifolius) Lectins Induce Apoptosis and Cell Arrest in G0/G1 by P53(Ser46) Phosphorylation in Colon Cancer Cells

Tepary Bean (Phaseolus acutifolius) Lectins Induce Apoptosis and Cell Arrest in G0/G1 by P53(Ser46) Phosphorylation in Colon Cancer Cells

Phosphoinositide specific phospholipase Cγ1 inhibition-driven autophagy caused cell death in human lung adenocarcinoma A549 cells in vivo and in vitro

Antitumor Potential of Marine and Freshwater Lectins

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