Emerging evidence suggests that both human stem cells and mature stromal cells can play an important role in the development and growth of human malignancies. In contrast to these tumor-promoting properties, we observed that in an in vivo model of Kaposi's sarcoma (KS), intravenously (i.v.) injected human mesenchymal stem cells (MSCs) home to sites of tumorigenesis and potently inhibit tumor growth. We further show that human MSCs can inhibit the in vitro activation of the Akt protein kinase within some but not all tumor and primary cell lines. The inhibition of Akt activity requires the MSCs to make direct cell–cell contact and can be inhibited by a neutralizing antibody against E-cadherin. We further demonstrate that in vivo, Akt activation within KS cells is potently down-regulated in areas adjacent to MSC infiltration. Finally, the in vivo tumor-suppressive effects of MSCs correlates with their ability to inhibit target cell Akt activity, and KS tumors engineered to express a constitutively activated Akt construct are no longer sensitive to i.v. MSC administration. These results suggest that in contrast to other stem cells or normal stromal cells, MSCs possess intrinsic antineoplastic properties and that this stem cell population might be of particular utility for treating those human malignancies characterized by dysregulated Akt.

Triple-negative breast cancer (TNBC) subtype is one of the most aggressive tumors with no definite receptor, hence has a limited number of effective chemotherapeutics. Doxorubicin (Dox) is the first-line drug for the TNBC treatment, acting as a DNA intercalator and topoisomerase II (Topo II) inhibitor; however, it has been observed to exhibit strong cardiotoxicity. Tanshinone IIA (Tan IIA) has a previously confirmed antitumor activity against breast cancer in addition to its well-known cardioprotective effect. In our study, molecular docking reveals the potential activity of Tan IIA as a DNA intercalator and Topo II inhibitor as a recommended possible mechanism of action compared to Dox as a reference drug. Moreover, we wanted to assess a new use for Tan IIA in the TNBC treatment in combination with Dox to broaden its therapeutic window and compensate for its cardiotoxic effects by the cardioprotective effects of Tan IIA. On performing the in vitro MTT assay to evaluate the cytotoxic effects of Dox, Tan IIA and their combinations at different concentrations of the MDA-MB-231 cell line revealed the potential activity of Tan IIA compared to Dox, in addition to the confirmed synergistic effects of Dox/Tan IIA combinations on TNBC cell lines. Furthermore, the analysis of the gene expression profiles of PI3K, mTOR, and AKT as anti-apoptotic genes were examined in the MDA-MB-231 cell line after the treatment with the IC50 of Dox, Tan IIA, and their combination, and compared to the control using PCR. These results confirmed the synergistic effect of the Dox/Tan IIA combination that exceeded that of Dox alone.

Breast cancer is the most common cancer in the Arab world and it ranked first among Saudi females. Doxorubicin (DOX), an anthracycline antibiotic is one of the most effective anticancer agents used to treat breast cancer. chronic cardiotoxicity is a major limiting factor of the use of doxorubicin. Therefore, our study was designed to assess the role of a natural product resveratrol (RSVL) on sensitization of human breast cancer cells (MCF-7) to the action of DOX in an attempt to minimize doxorubicin effective dose and thereby its side effects.