Supplement use and risk of cutaneous squamous cell carcinoma
Maryam M Asgari et al. J Am Acad Dermatol. 2011 Dec.
Background: Laboratory and epidemiologic studies suggest that certain dietary supplements may alter risk of cutaneous squamous cell carcinoma (SCC).
Objective:
We sought to examine the association between supplement use and SCC risk.
Methods:
Cases (n = 415) were defined as Kaiser Permanente Northern California members with a pathology-verified SCC in 2004 and control subjects (n = 415) were age-, sex-, and race-matched members with no history of skin cancer. Supplement use and SCC risk factors were ascertained by questionnaire. Associations of SCC with use of multivitamins; vitamins A, C, D, and E; and grape seed extract were estimated as odds ratios and 95% confidence intervals using conditional logistic regression. Models were adjusted for SCC risk factors and other supplement use.
Results:
Grape seed extract users had a significantly decreased risk of cutaneous SCC (adjusted odds ratio 0.26, confidence interval 0.08-0.89, P = .031). Multivitamin use was associated with a borderline significant reduction in SCC risk (adjusted odds ratio 0.71, confidence interval 0.51-1.00, P = .049). Use of vitamins A, C, D, and E was not associated with SCC risk.
Limitations:
The data may be prone to recall and selection bias because of the case-control design. No information was obtained on dose or duration of supplement use.
Conclusions:
Use of grape seed extract may be associated with a decreased risk of cutaneous SCC. The other supplements included in our study did not reveal clear associations with SCC risk.
Solanum incanum extract (SR-T100) induces human cutaneous squamous cell carcinoma apoptosis through modulating tumor necrosis factor receptor signaling pathway
Chin-Han Wu et al. J Dermatol Sci. 2011 Aug.
Background:
The Solanum species herbs have been used to treat cancer for centuries; however, the underlying mechanisms and effectiveness in vivo remain unclear.
Objectives:
SR-T100, extracted from the Solanum incanum, contains solamargine alkaloid as the main active ingredient. Here, we investigated the apoptosis-inducing effects of SR-T100 for targeting squamous cell carcinoma (SCC) in vitro and in vivo.
Methods:
We elucidated the mechanism by which SR-T100 induces apoptosis of human SCCs (A431, SCC4, SCC9, and SCC25) cells. The efficacy and safety issues were addressed regarding topical treatment of SR-T100 on UVB-induced cutaneous SCC of hairless mice and actinic keratoses (AKs) of human.
Results:
SR-T100 induces apoptosis in human SCCs cell lines by up-regulating the expressions of tumor necrosis factor receptors (TNFRs) and Fas, and downstream adaptors FADD/TRADD of the TNF-α and Fas ligand signaling cascades. SR-T100 also triggered the mitochondrial apoptotic pathway, as up-regulated cytochrome c and Bax, down-regulated Bcl-X(L). Animal experiments showed that all papillomas (35/35) and 27 of 30 UVB-induced microinvasive SCCs in hairless mice disappeared within 10 weeks after once-daily application of topical SR-T100. Furthermore, 13 patients, who suffered with 14 AKs, were treated with once-daily topical SR-T100 gel and 10 AKs cured after 16 weeks, showing negligible discomforts.
Conclusion:
Our studies indicate that SR-T100 induces apoptosis of SCC cells via death receptors and the mitochondrial death pathway. The high efficacy of SR-T100 in our preclinical trial suggests that SR-T100 is a highly promising herb for AKs and related disorders.
Anti-skin cancer properties of phenolic-rich extract from the pericarp of mangosteen (Garcinia mangostana Linn.)
Jing J Wang et al. Food Chem Toxicol. 2012 Sep.
Skin cancers are often resistant to conventional chemotherapy. This study examined the anti-skin cancer properties of crude ethanol extract of mangosteen pericarp (MPEE) on human squamous cell carcinoma A-431 and melanoma SK-MEL-28 lines. Significant dose-dependent reduction in% viability was observed for these cell lines, with less effect on human normal skin fibroblast CCD-1064Sk and keratinocyte HaCaT cell lines. Cell distribution in G(1) phase (93%) significantly increased after 10 μg/ml of MPEE versus untreated SK-MEL-28 cells (78%), which was associated with enhanced p21(WAF1) mRNA levels. In A-431 cells, 10 μg/ml MPEE significantly increased the sub G(1) peak (15%) with concomitant decrease in G(1) phase over untreated cells (2%). In A-431 cells, 10 μg/ml MPEE induced an 18% increase in early apoptosis versus untreated cells (2%). This was via caspase activation (15-, 3- and 4-fold increased caspse-3/7, 8, and 9 activities), and disruption of mitochondrial pathways (6-fold decreased mitochondrial membrane potential versus untreated cells). Real-time PCR revealed increased Bax/Bcl-2 ratio and cytochrome c release, and decreased Akt1. Apoptosis was significantly increased after MPEE treatment of SK-MEL-28 cells. Hence, MPEE showed strong anti-skin cancer effect on these two skin cancer cell lines, with potential as an anti-skin cancer agent.
Grape seed proanthocyanidines and skin cancer prevention: Inhibition of oxidative stress and protection of immune system Santosh K. Katiyar Abstract Overexposure of the skin to ultraviolet (UV) radiation has a variety of adverse effects on human health, including the development of skin cancers. There is a need to develop nutrition-based efficient chemopreventive strategies. The proanthocyanidins present in grape seeds (Vitis vinifera) have been shown to have some biological effects, including prevention of photocarcinogenesis. The present communication discusses the in vitro and in vivo studies of the possible protective effect of grape seed proanthocyanidins (GSPs) and the molecular mechanism for these effects. In SKH-1 hairless mice, dietary supplementation with GSPs is associated with a decrease of UVB-induced skin tumor development in terms of tumor incidence, tumor multiplicity, and a decrease in the malignant transformation of papillomas to carcinomas. It is suggested that the chemopreventive effects of dietary GSPs are mediated through the attenuation of UV-induced: (a) oxidative stress; (b) activation of mitogen-activated protein kinases and nuclear factor-κB signaling pathways; and (c) immunosuppression through alterations in immunoregulatory cytokines. Collectively, these studies indicate protective potential of GSPs against experimental photocarcinogenesis in SKH-1 hairless mice, and the possible mechanisms of action of GSPs, and suggest that dietary GSPs could be useful in the attenuation of the adverse UV-induced health effects in human skin.
Chemoprevention of lung and skin cancer by Beta vulgaris (beet) root extract
G J Kapadia et al. Cancer Lett. 1996.
Abstract
The in vitro inhibitory effect of Beta vulgaris (beet) root extract on Epstein-Barr virus early antigen (EBV-EA) induction using Raji cells revealed a high order of activity compared to capsanthin, cranberry, red onion skin and short and long red bell peppers. An in vivo anti-tumor promoting activity evaluation against the mice skin and lung bioassays also revealed a significant tumor inhibitory effect. The combined findings suggest that beetroot ingestion can be one of the useful means to prevent cancer.
Olive leaf extract and its main component oleuropein prevent chronic ultraviolet B radiation-induced skin damage and carcinogenesis in hairless mice
Yoshiyuki Kimura et al. J Nutr. 2009 Nov.
Chronic exposure to solar UV radiation damages skin, increasing its thickness and reducing its elasticity, and causes skin cancer. Our aim in this study was to examine the effects of an olive leaf extract and its component oleuropein on skin damage and the incidence of skin tumors caused by long-term UVB irradiation in hairless mice. Male hairless mice (5 wk old) were divided into 6 groups, including a non-UVB group, a vehicle-treated UVB group (control), 2 olive leaf extract-treated UVB groups, and 2 oleuropein-treated UVB groups. Five groups were UVB irradiated (36-180 mJ/cm(2)) 3 times each week for 30 wk and skin thickness and elasticity after UVB irradiation were measured every week. Olive leaf extract (300 and 1000 mg/kg) and oleuropein (10 and 25 mg/kg) were administered orally twice daily every day for 30 wk. The extract and oleuropein significantly inhibited increases in skin thickness and reductions in skin elasticity, and skin carcinogenesis and tumor growth.(cont.)
Molecular mechanism of apoptosis induction in skin cancer cells by the centipedegrass extract
2013
Srilatha Badaboina et al. BMC Complement Altern Med.
Background: Centipedegrass extract (CGE) is mainly composed of maysin and its derivatives, which are recognized internationally as natural compounds. Compared to other flavonoids, maysin has a unique structure in that mannose is bound to the flavonoid backbone. CGE exhibits some biological properties in that it can function as an anti-oxidant, anti-inflammatory, anti-adipogenic, and insecticidal. Whether CGE has other biological functions, such as anti-cancer activity, is unknown.
Methods: B16F1 (mouse) and SKMEL-5 (human) cells were treated with CGE, and their subsequent survival was determined using MTT assay. We performed a cell cycle analysis using propidium iodide (PI), and detected apoptosis using double staining with annexin V-FITC/PI. In addition, we examined mitochondrial membrane potentials using flow cytometry, as well as signaling mechanisms with an immunoblotting analysis.
Results: CGE inhibited skin cancer cell growth by arresting the cell cycle in the G2/M phase, and increased both early and late apoptotic cell populations without affecting normal cells. Furthermore, we observed mitochondrial transmembrane depolarization, increased cytochrome-c release, caspase-3 and caspase-7 activation, and increased poly ADP-ribose polymerase degradation. CGE also downregulated activation of p-AKT, p-glycogen synthase kinase-3β (GSK-3β), and p-BAD in a time-dependent manner. LY294002 inhibition of phosphoinositide 3-kinase (PI3K) significantly sensitized skin cancer cells, which led to an increase in CGE-induced apoptosis.
Conclusions: CGE controlled skin cancer cell growth by inhibiting the PI3K/AKT/GSK-3β signaling pathway and activating the effector caspases. This study is the first to demonstrate anti-cancer properties for CGE, and that CGE may be an effective therapeutic agent for treating skin cancer.
Durable response of cutaneous squamous cell carcinoma following high-dose peri-lesional injections of Viscum album extracts--a case report
2013
Case Reports
Paul Georg Werthmann et al. Phytomedicine.
Background:
Cutaneous squamous cell carcinoma (CSCC) is a common locally invasive skin cancer which rarely metastasises. First-line treatment is surgical excision, which is curative in most cases. Viscum album extract (VAE) is a widely used herbal cancer treatment with cytotoxic, apoptogenic and immunological effects, but has not been investigated in CSCC.
Case presentation:
A 78-year-old patient with histologically diagnosed CSCC refused surgical excision and was treated with peri-lesional high-dose VAE. After 10 months of treatment the CSCC had disappeared clinically. The patient has been recurrence-free for 4 years.
Conclusion:
The presented case shows clinical response of a CSCC to high-dose peri-lesional VAE injections. Further research on VAE in CSCC is warranted.
https://pubmed.ncbi.nlm.nih.gov/21664718/
Supplement use and risk of cutaneous squamous cell carcinoma
Maryam M Asgari et al. J Am Acad Dermatol. 2011 Dec.
Background: Laboratory and epidemiologic studies suggest that certain dietary supplements may alter risk of cutaneous squamous cell carcinoma (SCC).
Objective:
We sought to examine the association between supplement use and SCC risk.
Methods:
Cases (n = 415) were defined as Kaiser Permanente Northern California members with a pathology-verified SCC in 2004 and control subjects (n = 415) were age-, sex-, and race-matched members with no history of skin cancer. Supplement use and SCC risk factors were ascertained by questionnaire. Associations of SCC with use of multivitamins; vitamins A, C, D, and E; and grape seed extract were estimated as odds ratios and 95% confidence intervals using conditional logistic regression. Models were adjusted for SCC risk factors and other supplement use.
Results:
Grape seed extract users had a significantly decreased risk of cutaneous SCC (adjusted odds ratio 0.26, confidence interval 0.08-0.89, P = .031). Multivitamin use was associated with a borderline significant reduction in SCC risk (adjusted odds ratio 0.71, confidence interval 0.51-1.00, P = .049). Use of vitamins A, C, D, and E was not associated with SCC risk.
Limitations:
The data may be prone to recall and selection bias because of the case-control design. No information was obtained on dose or duration of supplement use.
Conclusions:
Use of grape seed extract may be associated with a decreased risk of cutaneous SCC. The other supplements included in our study did not reveal clear associations with SCC risk.
—
https://pubmed.ncbi.nlm.nih.gov/21612892/
Solanum incanum extract (SR-T100) induces human cutaneous squamous cell carcinoma apoptosis through modulating tumor necrosis factor receptor signaling pathway
Chin-Han Wu et al. J Dermatol Sci. 2011 Aug.
Background:
The Solanum species herbs have been used to treat cancer for centuries; however, the underlying mechanisms and effectiveness in vivo remain unclear.
Objectives:
SR-T100, extracted from the Solanum incanum, contains solamargine alkaloid as the main active ingredient. Here, we investigated the apoptosis-inducing effects of SR-T100 for targeting squamous cell carcinoma (SCC) in vitro and in vivo.
Methods:
We elucidated the mechanism by which SR-T100 induces apoptosis of human SCCs (A431, SCC4, SCC9, and SCC25) cells. The efficacy and safety issues were addressed regarding topical treatment of SR-T100 on UVB-induced cutaneous SCC of hairless mice and actinic keratoses (AKs) of human.
Results:
SR-T100 induces apoptosis in human SCCs cell lines by up-regulating the expressions of tumor necrosis factor receptors (TNFRs) and Fas, and downstream adaptors FADD/TRADD of the TNF-α and Fas ligand signaling cascades. SR-T100 also triggered the mitochondrial apoptotic pathway, as up-regulated cytochrome c and Bax, down-regulated Bcl-X(L). Animal experiments showed that all papillomas (35/35) and 27 of 30 UVB-induced microinvasive SCCs in hairless mice disappeared within 10 weeks after once-daily application of topical SR-T100. Furthermore, 13 patients, who suffered with 14 AKs, were treated with once-daily topical SR-T100 gel and 10 AKs cured after 16 weeks, showing negligible discomforts.
Conclusion:
Our studies indicate that SR-T100 induces apoptosis of SCC cells via death receptors and the mitochondrial death pathway. The high efficacy of SR-T100 in our preclinical trial suggests that SR-T100 is a highly promising herb for AKs and related disorders.
—
https://pubmed.ncbi.nlm.nih.gov/22705325/
Anti-skin cancer properties of phenolic-rich extract from the pericarp of mangosteen (Garcinia mangostana Linn.)
Jing J Wang et al. Food Chem Toxicol. 2012 Sep.
Skin cancers are often resistant to conventional chemotherapy. This study examined the anti-skin cancer properties of crude ethanol extract of mangosteen pericarp (MPEE) on human squamous cell carcinoma A-431 and melanoma SK-MEL-28 lines. Significant dose-dependent reduction in% viability was observed for these cell lines, with less effect on human normal skin fibroblast CCD-1064Sk and keratinocyte HaCaT cell lines. Cell distribution in G(1) phase (93%) significantly increased after 10 μg/ml of MPEE versus untreated SK-MEL-28 cells (78%), which was associated with enhanced p21(WAF1) mRNA levels. In A-431 cells, 10 μg/ml MPEE significantly increased the sub G(1) peak (15%) with concomitant decrease in G(1) phase over untreated cells (2%). In A-431 cells, 10 μg/ml MPEE induced an 18% increase in early apoptosis versus untreated cells (2%). This was via caspase activation (15-, 3- and 4-fold increased caspse-3/7, 8, and 9 activities), and disruption of mitochondrial pathways (6-fold decreased mitochondrial membrane potential versus untreated cells). Real-time PCR revealed increased Bax/Bcl-2 ratio and cytochrome c release, and decreased Akt1. Apoptosis was significantly increased after MPEE treatment of SK-MEL-28 cells. Hence, MPEE showed strong anti-skin cancer effect on these two skin cancer cell lines, with potential as an anti-skin cancer agent.
—
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2562900/
Grape seed proanthocyanidines and skin cancer prevention: Inhibition of oxidative stress and protection of immune system Santosh K. Katiyar Abstract Overexposure of the skin to ultraviolet (UV) radiation has a variety of adverse effects on human health, including the development of skin cancers. There is a need to develop nutrition-based efficient chemopreventive strategies. The proanthocyanidins present in grape seeds (Vitis vinifera) have been shown to have some biological effects, including prevention of photocarcinogenesis. The present communication discusses the in vitro and in vivo studies of the possible protective effect of grape seed proanthocyanidins (GSPs) and the molecular mechanism for these effects. In SKH-1 hairless mice, dietary supplementation with GSPs is associated with a decrease of UVB-induced skin tumor development in terms of tumor incidence, tumor multiplicity, and a decrease in the malignant transformation of papillomas to carcinomas. It is suggested that the chemopreventive effects of dietary GSPs are mediated through the attenuation of UV-induced: (a) oxidative stress; (b) activation of mitogen-activated protein kinases and nuclear factor-κB signaling pathways; and (c) immunosuppression through alterations in immunoregulatory cytokines. Collectively, these studies indicate protective potential of GSPs against experimental photocarcinogenesis in SKH-1 hairless mice, and the possible mechanisms of action of GSPs, and suggest that dietary GSPs could be useful in the attenuation of the adverse UV-induced health effects in human skin.
—
https://pubmed.ncbi.nlm.nih.gov/8620443/
Chemoprevention of lung and skin cancer by Beta vulgaris (beet) root extract
G J Kapadia et al. Cancer Lett. 1996.
Abstract
The in vitro inhibitory effect of Beta vulgaris (beet) root extract on Epstein-Barr virus early antigen (EBV-EA) induction using Raji cells revealed a high order of activity compared to capsanthin, cranberry, red onion skin and short and long red bell peppers. An in vivo anti-tumor promoting activity evaluation against the mice skin and lung bioassays also revealed a significant tumor inhibitory effect. The combined findings suggest that beetroot ingestion can be one of the useful means to prevent cancer.
—
https://pubmed.ncbi.nlm.nih.gov/19776181/
Olive leaf extract and its main component oleuropein prevent chronic ultraviolet B radiation-induced skin damage and carcinogenesis in hairless mice
Yoshiyuki Kimura et al. J Nutr. 2009 Nov.
Chronic exposure to solar UV radiation damages skin, increasing its thickness and reducing its elasticity, and causes skin cancer. Our aim in this study was to examine the effects of an olive leaf extract and its component oleuropein on skin damage and the incidence of skin tumors caused by long-term UVB irradiation in hairless mice. Male hairless mice (5 wk old) were divided into 6 groups, including a non-UVB group, a vehicle-treated UVB group (control), 2 olive leaf extract-treated UVB groups, and 2 oleuropein-treated UVB groups. Five groups were UVB irradiated (36-180 mJ/cm(2)) 3 times each week for 30 wk and skin thickness and elasticity after UVB irradiation were measured every week. Olive leaf extract (300 and 1000 mg/kg) and oleuropein (10 and 25 mg/kg) were administered orally twice daily every day for 30 wk. The extract and oleuropein significantly inhibited increases in skin thickness and reductions in skin elasticity, and skin carcinogenesis and tumor growth.(cont.)
—
https://pubmed.ncbi.nlm.nih.gov/24325618/
Molecular mechanism of apoptosis induction in skin cancer cells by the centipedegrass extract
2013 Srilatha Badaboina et al. BMC Complement Altern Med.
Background: Centipedegrass extract (CGE) is mainly composed of maysin and its derivatives, which are recognized internationally as natural compounds. Compared to other flavonoids, maysin has a unique structure in that mannose is bound to the flavonoid backbone. CGE exhibits some biological properties in that it can function as an anti-oxidant, anti-inflammatory, anti-adipogenic, and insecticidal. Whether CGE has other biological functions, such as anti-cancer activity, is unknown.
Methods: B16F1 (mouse) and SKMEL-5 (human) cells were treated with CGE, and their subsequent survival was determined using MTT assay. We performed a cell cycle analysis using propidium iodide (PI), and detected apoptosis using double staining with annexin V-FITC/PI. In addition, we examined mitochondrial membrane potentials using flow cytometry, as well as signaling mechanisms with an immunoblotting analysis.
Results: CGE inhibited skin cancer cell growth by arresting the cell cycle in the G2/M phase, and increased both early and late apoptotic cell populations without affecting normal cells. Furthermore, we observed mitochondrial transmembrane depolarization, increased cytochrome-c release, caspase-3 and caspase-7 activation, and increased poly ADP-ribose polymerase degradation. CGE also downregulated activation of p-AKT, p-glycogen synthase kinase-3β (GSK-3β), and p-BAD in a time-dependent manner. LY294002 inhibition of phosphoinositide 3-kinase (PI3K) significantly sensitized skin cancer cells, which led to an increase in CGE-induced apoptosis.
Conclusions: CGE controlled skin cancer cell growth by inhibiting the PI3K/AKT/GSK-3β signaling pathway and activating the effector caspases. This study is the first to demonstrate anti-cancer properties for CGE, and that CGE may be an effective therapeutic agent for treating skin cancer.
—
https://pubmed.ncbi.nlm.nih.gov/23394841/
Durable response of cutaneous squamous cell carcinoma following high-dose peri-lesional injections of Viscum album extracts--a case report
2013 Case Reports
Paul Georg Werthmann et al. Phytomedicine.
Background:
Cutaneous squamous cell carcinoma (CSCC) is a common locally invasive skin cancer which rarely metastasises. First-line treatment is surgical excision, which is curative in most cases. Viscum album extract (VAE) is a widely used herbal cancer treatment with cytotoxic, apoptogenic and immunological effects, but has not been investigated in CSCC.
Case presentation:
A 78-year-old patient with histologically diagnosed CSCC refused surgical excision and was treated with peri-lesional high-dose VAE. After 10 months of treatment the CSCC had disappeared clinically. The patient has been recurrence-free for 4 years.
Conclusion:
The presented case shows clinical response of a CSCC to high-dose peri-lesional VAE injections. Further research on VAE in CSCC is warranted.