Table 2:
Summary of complementary and alternative therapies evaluated for non-melanoma skin cancer with most available evidence.
| Agent | Mechanism of action | Effect in vitro / animal models | Effect in human participants | Potential for harm/toxicity | Level of evidence* |
|---|---|---|---|---|---|
| Botanical agents | |||||
| Goldenseal (Hydrastis canadensis) | • Inhibits glucose uptake inhibiting skin carcinogenesis | In vitro / Mice | No | • Potentially hinder glucose control in people with type 2 diabetes taking metformin (reduces 25% level) • May be safe taken alone, but there are not reliable studies that evaluate its safety. |
5 |
| Pond apple (Annona glabra) | • Down-regulates Bcl-2 gene • Up-regulates Bax gene • Antiproliferative effect |
In vitro | No | • Not reliable studies that evaluate its safety. | 5 |
| Bitter melon (Momordica charantia) | • Molecular pathway not available • Inhibits carcinogenesis |
Mice | No | • Not reliable studies that evaluate its safety. | 5 |
| Ginger (Zingiber officinale) | • Molecular pathway not available • Inhibits skin tumor initiation and promotion |
Mice | No | • Used safely on dietary supplement and topical use. • Abdominal discomfort, heartburn, diarrhea, and mouth and throat irritation, especially if taken in large doses. |
5 |
| Willow tree bark (Salix caprea) | • Inhibits oxidative stress and ornithine decarboxylase activity with anti-carcinogenesis effects | Mice | No | • Not reliable studies that evaluate its safety. | 5 |
| Frankincense (Boswellia serrata) | • Activates caspase-8 pathway and inhibits phosphorylation of the ERK 1/2 with antiproliferative effect | In vitro / Mice | Case reports | • When added in escharotic agents: subclinical extension of tumor. • Scarring and tissue damage, which could lead to disfiguring. |
5 |
| Sodom apple plant (Solanum sodomaeum) | • Not available. | In vitro / Mice | Case reports: cream formulation has shown efficacy on BCC, SCC, keratoacanthomas, and actinic keratosis at least 3 years after cessation of therapy | • Not reliable studies that evaluate its safety. | 5 |
| Plants of the genus Gelsemium | • Increases production of PCNA with antiproliferative and propaoptotic effect | In vitro / Mice | No | • Not reliable studies that evaluate its safety. | 5 |
| Polypodium leucotomos | • Decreases cyclobutane pyrimidine dimers • Decreases epidermal cells and dermal mast cell infiltration • Photoprotective effects against UVR. |
In vitro / Mice | Case reports: Increases the efficacy of photodynamic therapy in actinic keratosis | • Not reliable studies that evaluate its safety. | 5 |
| Phytochemicals | |||||
| Resveratrol | • Inhibits MMP-2 and MMP-9 secretion with antiproliferative effects on SCC models | In vitro | No | • May increase concentrations of pimozide (by CYP3A4 inhibition) | 5 |
| Cryptolepine | • Increases phosphorylation of • ATM/ATR, BRCA1, Chk1/Chk2 and γH2AX. • Activates of p53 signaling pathway • Downregulates of cyclin-dependent kinases, cyclin D1, cyclin A, cyclin E and proteins involved in cell division • Antiproliferative and propaoptotic effects |
In vitro | No | • Not reliable studies that evaluate its safety. | 5 |
| Apigenin | • Propapoptotic effect through TNFR- and Bcl-2-mediated pathway | In vitro: Enhances susceptibility of head and neck SCC to 5-fluorouracil and cisplatin | No | • Not reliable studies that evaluate its safety. | 5 |
| Curcumin | • Inhibits NF-κB signaling pathway, Akt, ERK1/2, STAT3 with antiproliferative and propaoptotic effects • Up-regulates miR-9 expression • Supresses Wnt/β-catenin signaling pathway • Decreases cyclin D1 level • Inhibits mTOR signaling pathway • Antiproliferative effects on oral SCC |
In vitro / Mice | Case reports and case series: chemoprevention of cancer, including arsenic Bowen’s disease and oral leukoplakia | • No treatment-related toxicity up to 8,000 mg/day | 4 |
| Curcuminoids | • Inhibites proliferation of HNO97 cell lines (Human oral squamous cell carcinoma). • Morphological changes of HNO97 cell lines: appearance of apoptosis. • Induces apoptosis of HNO97 cell lines in a time-dependent manner. • Alters the cell cycle distribution of HNO97 cell lines • DNA damage in HNO97 cell lines. • Supresses the colony-forming ability of HNO97 cell lines in a time-dependent manner. |
In vitro | Case reports | • Safely when taken orally or applied to the skin (turmeric) but lacks bioavailability. | 5 |
| Silymarin/Silibinin | • Protects against UVB-induced thymine dimer formation. • Promotes DNA repair. Apoptosis in damaged cells via an increase in p53 levels. • Target aberrant signaling pathways • Induction of anti-inflammatory responses (TNFα, IL-1α and COX-2 pathway). |
In vitro | No | • Milk thistle (contains silymarin) may lower blood sugar levels in people with type 2 diabetes | 5 |
| Herbal formulas | |||||
| “Black salve” | • Inhibits NF-κB with proapoptotic effect | In vitro | Case reports: complete BCC remission cases and residual infiltrating BCC. | • When added in escharotic agents: subclinical extension of tumor • Scarring and tissue damage, which could lead to disfiguring. |
5 |
| Cannabinoids | |||||
| Exogenous cannabinoids | • CB1 and CB2 activation shows antitumor effect in skin papillomas and NMSC in mice • Prevented growth and vascularization of malignant epidermal tumor cells |
In vitro / Mice | No | • Cannabis: risk of motor vehicle crashes, lower birth weight when consumed on pregnancy, orthostatic hypotension, severe mental illnesses (in predisposed). | 5 |
| Anandamide | • Elevated in skin tumor cells, leading to cell apoptosis | In vitro | No | • Not reliable studies that evaluate its safety. | 5 |
*
Level of evidence based on www.ebmconsult.com/articles/levels-of-evidence-and-recommendations