molecules Article Crosstalk of Cancer Signaling Pathways by Cyclic Hexapeptides and Anthraquinones from Rubia cordifolia Premalatha Balachandran 1,*,† , Mohamed Ali Ibrahim 1,*,† , Jin Zhang 1 , Mei Wang 1,2 , David S. Pasco 1 and Ilias Muhammad 1,* 1 National Center for Natural Products Research, Research Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi, Oxford, MS 38677, USA;
[email protected] (J.Z.);
[email protected] (M.W.);
[email protected] (D.S.P.) 2 Natural Products Utilization Research Unit, Agricultural Research Service, United States Department of Agriculture, Oxford, MS 38677, USA * Correspondence:
[email protected] (P.B.);
[email protected] (M.A.I.);
[email protected] (I.M.); Tel.: +1-662-915-3463 (P.B.); +1-662-915-1147 (M.A.I.); +1-662-915-1051 (I.M.) † P.B. and M.A.I. share equal authorship. Abstract: The anticancer activities of Rubia cordifolia and its constituents have been reported earlier, but their influence on the crosstalk of complex cancer-related signaling metabolic pathways (i.e., transcription factors; TF) has not yet been fully investigated. In this study, R. cordifolia root extract was subjected to the cancer signaling assay based bioactivity-guided fractionation, which yielded the following compounds viz., three anthraquinones, namely alizarin (1), purpurin (2), and emodin (3); two lignans, namely eudesmin (4) and compound 5; and two cyclic hexapeptides, namely deoxybouvardin RA-V (6), and a mixture of 6+9 (RA-XXI). The structures of the isolated compounds were determined by NMR spectroscopy and HRESIMS. The isolated compounds 1, 2, 3, 6, and a mixture of 6+9 were tested against a panel of luciferase reporter genes that assesses the activity Citation: Balachandran, P.; Ibrahim, of a wide-range of cancer-related signaling pathways.