Cleaved Caspase-3 Transcriptionally Regulates Angiogenesis-Promoting Chemotherapy Resistance

Bernard, Antoine; Chevrier, Sandy; Beltjens, Françoise; Dosset, Magalie; Viltard, Etienne; Lagrange, Anaïs; Dérangère, Valentin; Oudot, Alexandra; Ghiringhelli, François; Collin, Bertrand; Apétoh, Lionel; Féron, Olivier; Chen, Suzie; Arnould́, Laurent; Végran, Frédérique; Boidot, Romain

doi:10.1158/0008-5472.can-19-0840

Cited by 76 publications

(47 citation statements)

References 57 publications

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“…Low expression of caspase 3 in oral tumour tissues was also reported by (Li et al, 2017). An impairment in the status of caspase 3 and 9 has been reported frequently in cancer and its progression (Bernard et al, 2019). (Fong, 2006) have shown the down regula-tion of caspases in tumourigenesis.…”

Section: Resultsmentioning

confidence: 73%

Myrtenal averts apoptotic evasion of cancer cells in 7,12-dimethylbenz(a)anthracene induced experimental oral carcinogenesis

Buddhan

Manoharan

Muralinaidu

2020

ijrps

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Apoptotic avoidance is one of the foremost characteristic features of tumour cells. Apoptotic induction in cancer cells could thus help to identify new anticancer agents from the natural products. The present study has taken an effort to investigate the apoptotic efficacy of myrtenal, a monoterpene, in 7,12-dimethylbenz(a)anthracene (DMBA) induced oral carcinoma in male golden Syrian hamsters. The present study used the potent carcinogen, 7,12- dimethylbenz(a)anthracene, to develop oral tumours in the buccal pouches of the golden Syrian hamsters. Topical application of the above said carcinogen on the buccal mucosa (3 times a week for 14 weeks) resulted in well differentiated oral squamous cell carcinoma. The apoptotic potential of myrtenal was investigated using a spectrum of apoptotic markers, including pro-apoptotic and anti-apoptotic markers. Oral tumours developed in the buccal mucosa of hamsters showed higher expression of mutant p53 protein, Bcl-2 and lowered expression of Bax, Bad, Bid, caspase 3 and caspase 9. Myrtenal treatment at a dose of 230mg/kg bw orally to the hamsters treated with DMBA modulated the above said apoptotic markers towards tumour suppression or inhibition. The present findings thus suggests that the tumour preventive effect of myrtenal could partly be ascribed to its apoptotic induction potential during DMBA induced oral carcinogenesis.

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Section: Resultsmentioning

confidence: 73%

Myrtenal averts apoptotic evasion of cancer cells in 7,12-dimethylbenz(a)anthracene induced experimental oral carcinogenesis

Buddhan

Manoharan

Muralinaidu

2020

ijrps

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“…One of the best-known markers of apoptosis is proteolytic cleavage of pro-caspase-3 into its active form, caspase-3 (85). When cells undergo apoptosis, caspase-3 is activated to cleaved caspase-3, which promotes apoptosis (86). Here, ATO caused excessive ROS production and promoted apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Exploration of the hepatoprotective effect and mechanism of magnesium isoglycyrrhizinate in mice with arsenic trioxide‑induced acute liver injury

Liu

Zheng

et al. 2021

Mol Med Rep

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Arsenic trioxide (ATO)-induced hepatotoxicity limits the therapeutic effect of acute myelogenous leukemia treatment. Magnesium isoglycyrrhizinate (MgIG) is a natural compound extracted from licorice and a hepatoprotective drug used in liver injury. It exhibits anti-oxidant, anti-inflammatory and anti-apoptotic properties. The aim of the present study was to identify the protective action and underlying mechanism of MgIG against ATO-induced hepatotoxicity. A total of 50 mice were randomly divided into five groups (n=10/group): Control; ATO; MgIG and high-and low-dose MgIG + ATO. Following continuous administration of ATO for 7 days, the relative weight of the liver, liver enzyme, histological data, antioxidant enzymes, pro-inflammatory cytokines, cell apoptosis and changes in Kelch-like ECH-associated protein 1/nuclear factor erythroid 2-related factor 2 (Keap1-Nrf2) signaling pathway were observed. MgIG decreased liver injury, decreased the liver weight and liver index, inhibited oxidative stress and decreased the activity of glutathione, superoxide dismutase and catalase, production of reactive oxygen species and levels of pro-inflammatory cytokines, including IL-1β, IL-6 and TNF-α. Western blotting showed a decrease in Bax and caspase-3. There was decreased cleaved caspase-3 expression and increased Bcl-2 expression. MgIG notably activated ATO-mediated expression of Keap1 and Nrf2 in liver tissue. MgIG administration was an effective treatment to protect the liver from ATO-induced toxicity. MgIG maintained the level of Nrf2 in the liver and protected the antioxidative defense system to attenuate oxidative stress and prevent ATO-induced liver injury.

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“…In pancreatic cancer, for example, the activation of caspase-3 contributed to the proliferation of tumour cells (49) . Recently, caspase-3 activation has been shown to induce transcriptional changes, leading to positive regulation of genes involved in angiogenesis and negative regulation of genes involved in pro-apoptotic pathways (50) . Interestingly, during gestation, the increased replication of β-cells is accompanied by increased vascularisation of the islets (51) .…”

Section: Discussionmentioning

confidence: 99%

Protein malnutrition early in life increased apoptosis but did not alter the β-cell mass during gestation

et al. 2020

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We evaluated whether early life protein restriction alters structural parameters that affect β-cell mass on 15th d and 20th d of gestation in control-fed pregnant (CP), non-pregnant (CNP), protein-restricted pregnant (LPP) and non-pregnant (LPNP) rats from the foetal to the adult life stage as well as in protein-restricted rats that recovered after weaning (RP and RNP). On the 15th d of gestation the CNP group had a higher proportion of smaller islets, whereas the CP group exhibited a higher proportion of islets larger than the median. The β-cell mass was lower in the low-protein group than in the recovered and control groups. Gestation increased the β-cell mass, β-cell proliferation frequency and neogenesis frequency independently of the nutritional status. The apoptosis frequency was increased in the recovered groups compared to that in the other groups. On the 20th d of gestation, a higher proportion of islets smaller than the median was observed in the non-pregnant groups, whereas a higher proportion of islets larger than the median was observed in the RP, LPP and CP groups. β-cell mass was lower in the low-protein group than in the recovered and control groups, regardless of the physiological status. The β-cell proliferation frequency was lower, whereas the apoptosis rate was higher in recovered rats compared to those in the low protein and control rats. Thus, protein malnutrition early in life did not alter the mass of β cells, especially in the first two thirds of gestation, despite the increase in apoptosis.

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Cleaved Caspase-3 Transcriptionally Regulates Angiogenesis-Promoting Chemotherapy Resistance

Cited by 76 publications

References 57 publications

Myrtenal averts apoptotic evasion of cancer cells in 7,12-dimethylbenz(a)anthracene induced experimental oral carcinogenesis

Myrtenal averts apoptotic evasion of cancer cells in 7,12-dimethylbenz(a)anthracene induced experimental oral carcinogenesis

Exploration of the hepatoprotective effect and mechanism of magnesium isoglycyrrhizinate in mice with arsenic trioxide‑induced acute liver injury

Protein malnutrition early in life increased apoptosis but did not alter the β-cell mass during gestation

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