A novel chemopreventive mechanism for a traditional medicine: East Indian sandalwood oil induces autophagy and cell death in proliferating keratinocytes

Abstract

One of the primary components of the East Indian sandalwood oil (EISO) is α-santalol, a molecule that has been investigated for its potential use as a chemopreventive agent in skin cancer. Although there is some evidence that α-santalol could be an effective chemopreventive agent, to date, purified EISO has not been extensively investigated even though it is widely used in cultures around the world for its health benefits as well as for its fragrance and as a cosmetic. In the current study, we show for the first time that EISO-treatment of HaCaT keratinocytes results in a blockade of cell cycle progression as well as a concentration-dependent inhibition of UV-induced AP-1 activity, two major cellular effects known to drive skin carcinogenesis. Unlike many chemopreventive agents, these effects were not mediated through an inhibition of signaling upstream of AP-1, as EISO treatment did not inhibit UV-induced Akt, or MAPK activity. Low concentrations of EISO were found to induce HaCaT cell death, although not through apoptosis as annexin V and PARP cleavage were not found to increase with EISO treatment. However, plasma membrane integrity was severely compromised in EISO-treated cells, which may have led to cleavage of LC3 and the induction of autophagy. These effects were more pronounced in cells stimulated to proliferate with bovine pituitary extract and EGF prior to receiving EISO. Together, these effects suggest that EISO may exert beneficial effects upon skin, reducing the likelihood of promotion of pre-cancerous cells to actinic keratosis (AK) and skin cancer.

Inhibition of Akt Enhances the Chemopreventive Effects of Topical Rapamycin in Mouse Skin

“…The powder was then lysed and sonicated for Western blot analysis [16]. Cultured keratinocytes were lysed in RIPA lysis buffer including 1× HALT phosphatase/protease inhibitors (Invitrogen, Waltham, MA) and briefly sonicated on ice as described [34]. Protein concentration was determined using the Dc protein assay for both skin and cell culture lysates (BioRad, Hercules, PA).…”

“…Protein concentration was determined using the Dc protein assay for both skin and cell culture lysates (BioRad, Hercules, PA). Lysates were separated by SDS PAGE, transferred to PVDF membranes, blocked and probed with primary and secondary antibodies as described [34]. For keratinocytes, western blots shown are representative of n = 3.…”

The signaling involved in autophagy machinery in keratinocytes and therapeutic approaches for skin diseases

“…α-Santalol treatment could induce autophagy along with an increase of impaired plasma membrane integrity in the HaCaT cells, but not apoptosis [95]. Since the effect is more prominent in the proliferating cells than in the quiescent cells, cytotoxic treatment might be considered as an alternative way for the skin cancer therapy, which exerts less damage on normal cells via selective induction of autophagy.…”

Acorus gramineusand and Euodia ruticarpa Steam Distilled Essential Oils Exert Anti-Inflammatory Effects Through Decreasing Th1/Th2 and Pro-/Anti-Inflammatory Cytokine Secretion Ratios In Vitro

“…However, chronic inflammation is recognized as a potential risk factor [4], resulting in continuous and repeated inflammatory reactions that can cause other diseases such as cancer, cardiovascular disease, obesity and rheumatoid arthritis [5,6]. One strategy includes natural or synthetic products that are non-toxic to normal cells that can suppress or prevent initial carcinogenesis or the progression of premalignant cells in invasive diseases [7][8][9].…”