Combination of arabinogalactan and curcumin induces apoptosis in breast cancer cells in vitro and inhibits tumor growth via overexpression of p53 level in vivo.
OBJECTIVE
Increased mortality associated with breast cancer in women has spurred the studies to develop new drugs. Arabinogalactan (AG) and curcumin (Cur) are two natural products broadly explored in cancer therapy. Our major goal in the current study was to assess anticancer properties of combination these reagents in vitro on human breast cancer cells and in vivo utilizing animal model of breast cancer.


METHODS
We evaluated cell proliferation, apoptosis, cell cycle, and protein expression in vitro on MDA-MB-231 human breast cancer cells. For in vivo studies, murine breast cancer cells were implanted into BALB/c mice. Thereafter, volume of the developing tumor was calculated and expression of Ki67 and p53 proteins was evaluated to analyze cell proliferation and apoptosis.


RESULTS
Combination of AG and Cur significantly decreased cell growth in human breast cancer cells without any significant effect on normal cell growth. This combination could increase cell population in sub-G1 phase, which was indicative of apoptosis. Western blotting showed that the combination of AG and Cur significantly increased Bax/Bcl2 ratio as well as cleaved-caspase3 level in MDA-MB-231 cells. Combination of AG and Cur promoted apoptosis by increasing ROS level, changing mitochondrial membrane and reduction of glutathione. In addition, in vivo studies in mouse showed that this combination could inhibit the progression of breast tumors through over-expression of p53 and reduction of Ki67 levels.


CONCLUSIONS
Our findings suggest that the combination of AG and Cur is of great potential to induce apoptosis in breast cancer cells in vitro and in vivo.
Department of Animal Biology, School of Biology, College of Science, University of Tehran, Tehran, Iran.
Hassan
H
Moghtaderi
Department of Animal Biology, School of Biology, College of Science, University of Tehran, Tehran, Iran. Electronic address: hsepehri@khayam.ut.ac.ir.
Houri
H
Sepehri
Department of Animal Biology, School of Biology, College of Science, University of Tehran, Tehran, Iran.
Farnoosh
F
Attari
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology*; D005260:Female; D016193:G1 Phase / Q000187:drug effects; D005685:Galactans / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000096:biosynthesis; D009929:Organ Size / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D013194:Staining and Labeling; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D015430:Weight Gain / Q000187:drug effects
D051017:Apoptosis Regulatory Proteins; D005685:Galactans; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; D009569:Nitric Oxide; D005978:Glutathione; D003474:Curcumin; C005653:arabinogalactan
Apoptosis; Arabinogalactan; Breast cancer; Cell cycle; Cell growth; Curcumin