MAMDOOH GHONEUM, NARIMAN K. BADR EL-DIN, DOAA A. ALI and MAI ALAA EL-DEIN
Department of Otolaryngology, Drew University of Medicine and Science, Los Angeles, CA, U.S.A.;
Department of Zoology, Faculty of Science, University of Mansoura, Mansoura City, Egypt
Background: There is an increased interest in alternative treatments that reduce the toxicity of chemotherapy by lowering the drug concentration, whilst maintaining potency against cancer cells. Previous studies have demonstrated that arabinoxylan from rice bran, MGN-3/Biobran, sensitizes human breast cancer cells (BCC) to daunorubicin (DNR). In the present study, we further evaluated the ability of MGN-3 to sensitize cells to another chemotherapy agent, paclitaxel. Materials and Methods: Nonmetastatic MCF-7 (human BCC) and metastatic 4T1 (murine BCC) cells were cultured with different concentrations of paclitaxel in the presence or absence of MGN-3. Cell survival, DNA damage, and cell proliferation were examined.
Results: MGN-3 increased the susceptibility of both types of cancer cells to paclitaxel by over 100-fold. Mechanistically, MGN-3 works synergistically with paclitaxel by causing DNA damage, enhancing apoptosis, and inhibiting cell proliferation in 4T1 cells.
Conclusion: Our data demonstrate that MGN-3 is an effective chemosensitizer and may represent a novel adjuvant for the treatment of metastatic breast cancer. Cancer remains the largest cause of mortality in the world, claiming over six million lives each year. Chemotherapy is considered the cornerstone of treatment for many types of cancers. However, many chemotherapeutic agents exhibit dose-limiting toxicities (1-5). Therefore, there is increasing interest in identifying compounds that may increase the sensitivity of cancer cells to conventional chemotherapeutic agents, thus reducing chemotherapeutic-related toxicity (6-9). Early studies from our laboratory have shown that arabinoxylan rice bran, MGN-3/Biobran, sensitizes human leukemia HUT 78 cells to apoptosis induced by antibody to cluster of differentiation 95 (CD95) (10), and human breast cancer cells (BCCs) to daunorubicin in vitro (11).