Autophagy inhibitor 3-methyladenine potentiates apoptosis induced by dietary tocotrienols in breast cancer cells.
BACKGROUND
Tocomin® represents commercially available mixture of naturally occurring tocotrienols (T3s) and tocopherols extracted from palm oil/palm fruits that possess powerful antioxidant, anticancer, neuro/cardioprotective and cholesterol-lowering properties. Cellular autophagy represents a defense mechanism against oxidative stress and several anticancer compounds. Recently, we reported that T3s induce apoptosis and endoplasmic reticulum stress in breast cancer cells.


METHODS
We studied the effects of Tocomin® on MCF-7 and MDA-MB 231 breast cancer cells and non-tumor MCF-10A cells.


RESULTS
Tocomin® inhibited cell proliferation and induced apoptosis in both MCF-7 and MDA-MB 231 breast cancer cell lines without affecting the viability of MCF-10A cells. We also showed that Tocomin® negatively modulates phosphoinositide 3-kinase and mTOR pathways and induces cytoprotective autophagic response in triple negative MDA-MB 231 cells. Lastly, we demonstrate that autophagy inhibitor 3-methyladenine (3-MA) potentiated the apoptosis induced by Tocomin® in MDA-MB 231 cells.


CONCLUSIONS
Together, our data indicate anticancer effects of Tocomin® in breast cancer cells, which is potentiated by the autophagy inhibitor 3-MA.
Cancer Research Laboratory, Department of Biology and Chemistry, University of the District of Columbia, Building 44, Room 312, 4200 Connecticut Avenue, NW, Washington, DC, 20008, USA.
Anh Thu
AT
Tran
Malathi
M
Ramalinga
Habib
H
Kedir
Robert
R
Clarke
Deepak
D
Kumar
D000225:Adenine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000494:pharmacology*; D000975:Antioxidants / Q000009:adverse effects / Q000737:chemistry / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D019587:Dietary Supplements / Q000009:adverse effects; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D042361:Mammary Glands, Human / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D024508:Tocotrienols / Q000009:adverse effects / Q000819:agonists* / Q000378:metabolism
D000964:Antimetabolites, Antineoplastic; D000975:Antioxidants; C570135:Tocomin; D024508:Tocotrienols; C025946:3-methyladenine; D000225:Adenine