santalol and Breast-Neoplasms

Alpha-santalol, a terpenoid found in sandalwood oil has been shown to inhibit breast cancer cell growth in vitro by inducing apoptosis, but the mechanisms underlying the growth inhibitory effects of alpha-santalol are not fully understood. In this study, we demonstrate that α-santalol treatment targets Wnt/β-catenin pathway to inhibit migration of cultured breast cancer cells.. Migration assays, immunoblotting and immunofluorescence were used to examine the mechanism of action of a-santalol in breast cancer cells.. Exposure of MDA-MB 231 and MCF-7 cells to α-santalol resulted in a significant reduction in their migratory potential and wound healing ability. In addition, α-santalol affected the localization of β-catenin from cytosol to nucleus in MDA-MB 231 cells.. Alpha-santalol inhibited migration of breast cancer cells may be mediated, in part, by targeting Wnt//β-catenin pathway. β-catenin represents an important target of α-santalol's response for future pre-clinical studies.

Topics: Apoptosis; beta Catenin; Breast Neoplasms; Cell Line, Tumor; Cell Movement; Female; Humans; MCF-7 Cells; Plant Oils; Polycyclic Sesquiterpenes; Sesquiterpenes; Signal Transduction; Wnt Signaling Pathway; Wound Healing

Almost all breast cancers originate from epithelial cells lining the milk ducts in the breast. To this end, the study investigated the feasibility of localized transdermal delivery of α-santalol, a natural chemopreventive agent to the breast.. Different α-santalol formulations (cream, solution and microemulsion) were developed and the in vitro permeability was studied using excised animal (porcine and rat) and human breast skin/mammary papilla (nipple). The in vivo biodistribution and efficacy studies were conducted in female rats. A chemical carcinogenesis model of breast cancer was used for the efficacy studies.. Phospholipid based α-santalol microemulsion showed the highest penetration through the nipple and breast skin. Delivery of α-santalol through the entire breast (breast skin and nipple) in vivo in rats resulted in significantly higher concentration in the mammary gland compared to transdermal delivery through the breast skin or nipple. There was no measurable α-santalol concentration in the blood. Transdermal delivery of α-santalol reduced the tumor incidence and tumor multiplicity. Furthermore, the tumor size was significantly reduced with α-santalol treatment.. The findings from this study demonstrate the feasibility of localized transdermal delivery of α-santalol for chemoprevention of breast cancer.

Topics: Administration, Cutaneous; Animals; Anticarcinogenic Agents; Breast; Breast Neoplasms; Chemoprevention; Female; Humans; Nipples; Polycyclic Sesquiterpenes; Rats; Rats, Sprague-Dawley; Sesquiterpenes; Skin Absorption; Swine

α-Santalol, a terpenoid found in sandalwood oil, has been shown to inhibit cancer cell growth in vitro by inducing apoptosis. This study was performed to investigate the anticancer properties of α-santalol associated with the induction of apoptosis in cultured MCF-7 [estrogen receptor (ER)-positive, and wild-type p53)] and MDA-MB-231 (ER-negative and mutant p53) breast cancer cells.. Expression of major proteins examined in the study were determined using a standard western blot protocol and analyzed by LICOR-Odyssey infra-red scanner. Total protein levels of survivin were confirmed by survivin enzyme-linked immunosorbent assay (ELISA) kit. Cell viability was assessed by the trypan blue dye exclusion assay, and caspase-3 activity was determined by caspase-3 (active) ELISA kit.. Treatment of breast cancer cells for 6 and 9 h with α-santalol (20, and 40 μM) resulted in statistically significant concentration-dependent down-regulation of survivin. Phosphorylated protein kinase B (pAKT) levels were found to be slightly up-regulated despite the down-regulation of survivin. Pharmacological inhibition of the phosphoinositide 3-kinase - protein kinase B (PI3K-AKT) pathway did not result in a synergistic/additive increase in cell death or caspase-3 activity caused by α-santalol.. The study reveals that survivin down-regulation by α-santalol in breast cancer cells is not mediated through the PI3K-AKT pathway.

Topics: Antineoplastic Agents; Apoptosis; Breast Neoplasms; Cell Line, Tumor; Cell Proliferation; Chromones; Down-Regulation; Female; Gene Expression Regulation, Neoplastic; Humans; Inhibitor of Apoptosis Proteins; MAP Kinase Signaling System; MCF-7 Cells; Morpholines; Polycyclic Sesquiterpenes; Sesquiterpenes; Survivin

Anticancer efficacy and the mechanism of action of α-santalol, a terpenoid isolated from sandalwood oil, were investigated in human breast cancer cells by using p53 wild-type MCF-7 cells as a model for estrogen receptor (ER)-positive and p53 mutated MDA-MB-231 cells as a model for ER-negative breast cancer. α-Santalol inhibited cell viability and proliferation in a concentration and time-dependent manner in both cells regardless of their ER and/or p53 status. However, α-santalol produced relatively less toxic effect on normal breast epithelial cell line, MCF-10A. It induced G2/M cell cycle arrest and apoptosis in both MCF-7 and MDA-MB-231 cells. Cell cycle arrest induced by α-santalol was associated with changes in the protein levels of BRCA1, Chk1, G2/M regulatory cyclins, Cyclin dependent kinases (CDKs), Cell division cycle 25B (Cdc25B), Cdc25C and Ser-216 phosphorylation of Cdc25C. An up-regulated expression of CDK inhibitor p21 along with suppressed expression of mutated p53 was observed in MDA-MB-231 cells treated with α-santalol. On the contrary, α-santalol did not increase the expression of wild-type p53 and p21 in MCF-7 cells. In addition, α-santalol induced extrinsic and intrinsic pathways of apoptosis in both cells with activation of caspase-8 and caspase-9. It led to the activation of the executioner caspase-6 and caspase-7 in α-santalol-treated MCF-7 cells and caspase-3 and caspase-6 in MDA-MB-231 cells along with strong cleavage of poly(ADP-ribose) polymerase (PARP) in both cells. Taken together, this study for the first time identified strong anti-neoplastic effects of α-santalol against both ER-positive and ER-negative breast cancer cells.

Topics: Antineoplastic Agents; Apoptosis; Breast Neoplasms; Cell Division; Cell Line, Tumor; Cell Proliferation; Female; Flow Cytometry; G2 Phase; Humans; In Situ Nick-End Labeling; Polycyclic Sesquiterpenes; Receptors, Estrogen; Sesquiterpenes